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  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 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

    International Nuclear Information System (INIS)

    Mita, Hiroaki; Yanagihara, Kazuyoshi; Fujita, Masahiro; Hosokawa, Masao; Kusano, Masanobu; Sabau, Sorin Vasile; Tatsumi, Haruyuki; Imai, Kohzoh; Shinomura, Yasuhisa; Tokino, Takashi; Toyota, Minoru; Aoki, Fumio; Akashi, Hirofumi; Maruyama, Reo; Sasaki, Yasushi; Suzuki, Hiromu; Idogawa, Masashi; Kashima, Lisa

    2009-01-01

    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. 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. 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-type KRAS resulted in the inhibition of cell growth and

  3. The KRAS Strip Assay for detection of KRAS mutation in Egyptian patients with colorectal cancer (CRC): A pilot study

    International Nuclear Information System (INIS)

    Abd El Kader, Y.; Safwat, E.; Kassem, H.A.; Kassem, N.M.; Emera, G.

    2013-01-01

    Background: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefltinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. Purpose: Detection of KRAS mutation in Egyptian colorectal cancer (CRC) patients by the KRAS Strip Assay. Methods: Examination of 20 colorectal cancer (CRC) patients is done to detect KRAS mutations by KRAS Strip Assay. For the Strip Assay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. Results: Among 20 patients, KRAS mutations were identified in 80% of patients by the KRAS Strip Assay. Conclusions: Our preliminary results suggest that KRAS Strip Assay is an alternative to protocols currently in use for KRAS mutation detection

  4. 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.

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

    International Nuclear Information System (INIS)

    Lee, So-Young; Lim, Jae-Cheong; Cho, Eun-Ha; Jung, Sung-Hee

    2016-01-01

    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 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.

  6. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

    Directory of Open Access Journals (Sweden)

    Nicolas Piton

    2015-01-01

    Full Text Available KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27% and specificity (64% in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100% and specificity (100% in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

  7. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

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    Borrini, Francesco; Bolognese, Antonio; Lamy, Aude; Sabourin, Jean-Christophe

    2015-01-01

    KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer. PMID:25983749

  8. 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.

  9. One-step isothermal detection of multiple KRAS mutations by forming SNP specific hairpins on a gold nanoshell.

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    Chung, Chan Ho; Kim, Joong Hyun

    2018-04-24

    We developed a one-step isothermal method for typing multiple KRAS mutations using a designed set of primers to form a hairpin on a gold nanoshell upon being ligated by a SNP specific DNA ligase after binding of targets. As a result, we could detect as low as 20 attomoles of KRAS mutations within 1 h.

  10. New comprehensive denaturing-gradient-gel-electrophoresis assay for KRAS mutation detection applied to paraffin-embedded tumours

    NARCIS (Netherlands)

    Hayes, VM; Westra, JL; Verlind, E; Bleeker, W; Plukker, JT; Hofstra, RMW; Buys, CHCM

    2000-01-01

    A comprehensive mutation detection assay is presented for the entire coding region and all splice site junctions of the KRAS oncogene. The assay is based on denaturing gradient gel electrophoresis and applicable to archival paraffin-embedded tumour material. All KRAS amplicons are analysed within

  11. 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.

  12. A novel approach to detect KRAS/BRAF mutation for colon cancer: Highly sensitive simultaneous detection of mutations and simple pre-treatment without DNA extraction.

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    Suzuki, Shun-Ichi; Matsusaka, Satoshi; Hirai, Mitsuharu; Shibata, Harumi; Takagi, Koichi; Mizunuma, Nobuyuki; Hatake, Kiyohiko

    2015-07-01

    It has been reported that colon cancer patients with KRAS and BRAF mutations that lie downstream of epidermal growth factor receptor (EGFR) acquire resistance against therapy with anti‑EGFR antibodies, cetuximab and panitumumab. On the other hand, some reports say KRAS codon 13 mutation (p.G13D) has lower resistance against anti-EGFR antibodies, thus there is a substantial need for detection of specific KRAS mutations. We have established a state-of-the-art measurement system using QProbe (QP) method that allows simultaneous measurement of KRAS codon 12/13, p.G13D and BRAF mutation, and compared this method against Direct Sequencing (DS) using 182 specimens from colon cancer patients. In addition, 32 biopsy specimens were processed with a novel pre-treatment method without DNA purification in order to detect KRAS/BRAF. As a result of KRAS mutation measurement, concordance rate between the QP method and DS method was 81.4% (144/177) except for the 5 specimens that were undeterminable. Among them, 29 specimens became positive with QP method and negative with DS method. BRAF was measured with QP method only, and the mutation detection rate was 3.9% (6/153). KRAS measurement using a simple new pre-treatment method without DNA extraction resulted in 31 good results out of 32, all of them matching with the DS method. We have established a simple but highly sensitive simultaneous detection system for KRAS/BRAF. Moreover, introduction of the novel pre-treatment technology eliminated the inconvenient DNA extraction process. From this research achievement, we not only anticipate quick and accurate results returned in the clinical field but also contribution in improving the test quality and work efficiency.

  13. 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.

  14. KRAS mutation detection in colorectal cancer by a commercially available gene chip array compares well with Sanger sequencing.

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    French, Deborah; Smith, Andrew; Powers, Martin P; Wu, Alan H B

    2011-08-17

    Binding of a ligand to the epidermal growth factor receptor (EGFR) stimulates various intracellular signaling pathways resulting in cell cycle progression, proliferation, angiogenesis and apoptosis inhibition. KRAS is involved in signaling pathways including RAF/MAPK and PI3K and mutations in this gene result in constitutive activation of these pathways, independent of EGFR activation. Seven mutations in codons 12 and 13 of KRAS comprise around 95% of the observed human mutations, rendering monoclonal antibodies against EGFR (e.g. cetuximab and panitumumab) useless in treatment of colorectal cancer. KRAS mutation testing by two different methodologies was compared; Sanger sequencing and AutoGenomics INFINITI® assay, on DNA extracted from colorectal cancers. Out of 29 colorectal tumor samples tested, 28 were concordant between the two methodologies for the KRAS mutations that were detected in both assays with the INFINITI® assay detecting a mutation in one sample that was indeterminate by Sanger sequencing and a third methodology; single nucleotide primer extension. This study indicates the utility of the AutoGenomics INFINITI® methodology in a clinical laboratory setting where technical expertise or access to equipment for DNA sequencing does not exist. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    Dilara Fatma Akin

    2015-10-01

    Oct 1, 2015 ... sarcoma viral oncogene homolog (KRAS), and Casitas B-cell ... AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing ... Methods: Eight patients who were diagnosed with pediatric AML at Losante ..... mutations in pre-leukemic stem cells in acute myeloid leukemia.

  16. Highly sensitive KRAS mutation detection from formalin-fixed paraffin-embedded biopsies and circulating tumour cells using wild-type blocking polymerase chain reaction and Sanger sequencing.

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    Huang, Meggie Mo Chao; Leong, Sai Mun; Chua, Hui Wen; Tucker, Steven; Cheong, Wai Chye; Chiu, Lily; Li, Mo-Huang; Koay, Evelyn Siew-Chuan

    2014-08-01

    Among patients with colorectal cancer (CRC), KRAS mutations were reported to occur in 30-51 % of all cases. CRC patients with KRAS mutations were reported to be non-responsive to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment in many clinical trials. Hence, accurate detection of KRAS mutations would be critical in guiding the use of anti-EGFR MoAb therapies in CRC. In this study, we carried out a detailed investigation of the efficacy of a wild-type (WT) blocking real-time polymerase chain reaction (PCR), employing WT KRAS locked nucleic acid blockers, and Sanger sequencing, for KRAS mutation detection in rare cells. Analyses were first conducted on cell lines to optimize the assay protocol which was subsequently applied to peripheral blood and tissue samples from patients with CRC. The optimized assay provided a superior sensitivity enabling detection of as little as two cells with mutated KRAS in the background of 10(4) WT cells (0.02 %). The feasibility of this assay was further investigated to assess the KRAS status of 45 colorectal tissue samples, which had been tested previously, using a conventional PCR sequencing approach. The analysis showed a mutational discordance between these two methods in 4 of 18 WT cases. Our results present a simple, effective, and robust method for KRAS mutation detection in both paraffin embedded tissues and circulating tumour cells, at single-cell level. The method greatly enhances the detection sensitivity and alleviates the need of exhaustively removing co-enriched contaminating lymphocytes.

  17. In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells.

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    El-Heliebi, Amin; Hille, Claudia; Laxman, Navya; Svedlund, Jessica; Haudum, Christoph; Ercan, Erkan; Kroneis, Thomas; Chen, Shukun; Smolle, Maria; Rossmann, Christopher; Krzywkowski, Tomasz; Ahlford, Annika; Darai, Evangelia; von Amsberg, Gunhild; Alsdorf, Winfried; König, Frank; Löhr, Matthias; de Kruijff, Inge; Riethdorf, Sabine; Gorges, Tobias M; Pantel, Klaus; Bauernhofer, Thomas; Nilsson, Mats; Sedlmayr, Peter

    2018-03-01

    Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms. We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients. In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts. Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices. © 2017 American Association for Clinical Chemistry.

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

    African Journals Online (AJOL)

    Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing (NGS) analysis. In addition, association between found variants and mutations of Januse Kinase-2 (JAK2) and Fms Related ...

  19. KRAS detection in colonic tumors by DNA extraction from FTA paper: the molecular touch-prep.

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    Petras, Melissa L; Lefferts, Joel A; Ward, Brian P; Suriawinata, Arief A; Tsongalis, Gregory J

    2011-12-01

    DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue is usually more degraded and contains more polymerase chain reaction (PCR) inhibitors than DNA isolated from nonfixed tissue. In addition, the tumor size and cellular heterogeneity found in tissue sections can often impact testing for molecular biomarkers. As a potential remedy to this situation, we evaluated the use of Whatman FTA paper cards for collection of colorectal tumor samples before tissue fixation and for isolation of DNA for use in a real-time PCR-based KRAS mutation assay. Eleven colon tumor samples were collected by making a cut into the fresh tumor and applying the Whatman FTA paper to the cut surface. Matched FFPE tissue blocks from these tumors were also collected for comparison. KRAS mutation analysis was carried out using the Applied Biosystems 7500 Fast Real-time PCR System using 7 independent custom TaqMan PCR assays. Of the 11 colon tumors sampled, 6 were positive for KRAS mutations in both the Whatman FTA paper preparations and corresponding FFPE samples. Whatman FTA paper cards for collection of colorectal tumor samples before tissue fixation and for isolation of DNA have many advantages including ease of use, intrinsic antimicrobial properties, long storage potential (stability of DNA over time), and a faster turnaround time for results. Extracted DNA should be suitable for most molecular diagnostic assays that use PCR techniques. This novel means of DNA preservation from surgical specimens would benefit from additional study and validation as a dependable and practical technique to preserve specimens for molecular testing.

  20. 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.<...

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

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

    2016-01-01

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

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

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    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.

  3. Detection of Arthritis by Joint Scanning

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    Maxfield, W. S. [Dept, of Radiology, Louisiana State University School of Medicine, New Orleans, LA (United States); Weiss, T. E.; Tutton, R. H.; Hidalgo, J. U. [Ochsner Clinic and Ochsner Foundation Hospital, New Orleans, LA (United States)

    1969-05-15

    Detection and identification of early arthritis is frequently difficult with routine methods. Several tracers, {sup 131}I human serum albumin (25 {mu}Ci/10 lb), {sup 99m}Tc human serum albumin (1-3 mCi), {sup 131}I iodipamide (40 {mu}Ci/10 lb), and {sup 99m}Tc pertechnetate (10 mCi), have been employed for joint scanning to detect synovitis produced by arthritis in joints of the extremities. When administered intravenously, the 25% increase in localization of these tracers in the synovial membrane, if there is active synovitis, can be demonstrated by scintillation scanning. This ability to detect synovitis at an early stage enables the joint scan to show areas of active synovitis not demonstrated on roentgenograms. The scan may objectively confirm or disprove questionable physical findings. From this standpoint the technique has been useful in determining whether joint pain is functional or due to arthritis as a negative localization tends to rule out active synovitis as the cause of the pain. The scan demonstration of a positive localization of the tracer in several joints when only one area is symptomatic is evidence that joint pain is due to systemic disease. The short half-life tracera permit serial studies to follow the course of an arthritis process. Use of {sup 99m}Tc pertechnetate and an Anger camera have made joint scanning a practical technique for clinical use. A review of the accuracy of joint scanning in 130 cases as compared to roentgenograms is presented. (author)

  4. Admittance Scanning for Whole Column Detection.

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    Stamos, Brian N; Dasgupta, Purnendu K; Ohira, Shin-Ichi

    2017-07-05

    Whole column detection (WCD) is as old as chromatography itself. WCD requires an ability to interrogate column contents from the outside. Other than the obvious case of optical detection through a transparent column, admittance (often termed contactless conductance) measurements can also sense changes in the column contents (especially ionic content) from the outside without galvanic contact with the solution. We propose here electromechanically scanned admittance imaging and apply this to open tubular (OT) chromatography. The detector scans across the column; the length resolution depends on the scanning velocity and the data acquisition frequency, ultimately limited by the physical step resolution (40 μm in the present setup). Precision equal to this step resolution was observed for locating an interface between two immiscible liquids inside a 21 μm capillary. Mechanically, the maximum scanning speed was 100 mm/s, but at 1 kHz sampling rate and a time constant of 25 ms, the highest practical scan speed (no peak distortion) was 28 mm/s. At scanning speeds of 0, 4, and 28 mm/s, the S/N for 180 pL (zone length of 1.9 mm in a 11 μm i.d. column) of 500 μM KCl injected into water was 6450, 3850, and 1500, respectively. To facilitate constant and reproducible contact with the column regardless of minor variations in outer diameter, a double quadrupole electrode system was developed. Columns of significant length (>1 m) can be readily scanned. We demonstrate its applicability with both OT and commercial packed columns and explore uniformity of retention along a column, increasing S/N by stopped-flow repeat scans, etc. as unique applications.

  5. Detection of EGFR and KRAS mutations in fine-needle aspirates stored on Whatman FTA cards: is this the tool for biobanking cytological samples in the molecular era?

    Science.gov (United States)

    da Cunha Santos, Gilda; Liu, Ni; Tsao, Ming-Sound; Kamel-Reid, Suzanne; Chin, Kayu; Geddie, William R

    2010-12-25

    The aims of this study were to compare the quality of DNA recovered from fine-needle aspirates (FNAs) stored on Whatman FTA cards with that retrieved from corresponding cell blocks and to determine whether the DNA extracted from the cards is suitable for multiple mutation analyses. FNAs collected from 18 resected lung tumors and cell suspensions from 4 lung cancer cell lines were placed on FTA Indicating Micro Cards and further processed to produce paired formalin-fixed paraffin-embedded (FFPE) cell blocks. Fragment analysis was used for the detection of EGFR exon 19 deletion, and direct sequencing for detection of EGFR exon 21 L858R mutation and exon 2 deletion of KRAS. Corresponding FFPE tissue sections from 2 resection specimens were also tested. Analyses were successful with all FNAs and lung cancer-derived cell lines collected on cards. Polymerase chain reaction failed in 2 cell blocks. For FNAs collected on cards, 5 cases showed EGFR and 3 showed KRAS mutations. Eleven cases were wild type. With cell blocks, 4 cases were found to harbor KRAS and 4 harbored EGFR mutations. All lung cancer-derived cell lines tested positive for their respective mutations, and there was complete agreement between card and cell block FNA samples for EGFR exon 21. For EGFR exon 19, 1 of 18 cases showed discordant results between the card and cell block, and for KRAS 1 of 17. The two resection specimens tested gave concordant results with the FTA card. Storage of cytologic material on FTA cards can maximize and simplify sample procurement for multiple mutational analyses with results similar to those from cell blocks.

  6. Validation of a Multiplex Allele-Specific Polymerase Chain Reaction Assay for Detection of KRAS Gene Mutations in Formalin-Fixed, Paraffin-Embedded Tissues from Colorectal Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Sirirat Seekhuntod

    Full Text Available Patients with KRAS mutations do not respond to epidermal growth factor receptor (EGFR inhibitors and fail to benefit from adjuvant chemotherapy. Mutation analysis of KRAS is needed before starting treatment with monoclonal anti-EGFR antibodies in patients with metastatic colorectal cancer (mCRC. The objective of this study is to develop a multiplex allele-specific PCR (MAS-PCR assay to detect KRAS mutations.We developed a single-tube MAS-PCR assay for the detection of seven KRAS mutations (G12D, G12A, G12R, G12C, G12S, G12V, and G13D. We performed MAS-PCR assay analysis for KRAS on DNA isolated from 270 formalin-fixed paraffin-embedded (FFPE colorectal cancer tissues. Sequences of all 270 samples were determined by pyrosequencing. Seven known point-mutation DNA samples diluted with wild-type DNA were assayed to determine the limitation of detection and reproducibility of the MAS-PCR assay.Overall, the results of MAS-PCR assay were in good concordance with pyrosequencing, and only seven discordant samples were found. The MAS-PCR assay reproducibly detected 1 to 2% mutant alleles. The most common mutations were G13D in codon 13 (49.17%, G12D (25.83% and G12V (12.50% in codon 12.The MAS-PCR assay provides a rapid, cost-effective, and reliable diagnostic tool for accurate detection of KRAS mutations in routine FFPE colorectal cancer tissues.

  7. 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

    International Nuclear Information System (INIS)

    Schneider, Mandy; Scholtka, Bettina; Gottschalk, Uwe; Faiss, Siegbert; Schatz, Daniela; Berghof-Jäger, Kornelia; Steinberg, Pablo

    2010-01-01

    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

  8. 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.

  9. 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.

  10. Introduction of the hybcell-based compact sequencing technology and comparison to state-of-the-art methodologies for KRAS mutation detection.

    Science.gov (United States)

    Zopf, Agnes; Raim, Roman; Danzer, Martin; Niklas, Norbert; Spilka, Rita; Pröll, Johannes; Gabriel, Christian; Nechansky, Andreas; Roucka, Markus

    2015-03-01

    The detection of KRAS mutations in codons 12 and 13 is critical for anti-EGFR therapy strategies; however, only those methodologies with high sensitivity, specificity, and accuracy as well as the best cost and turnaround balance are suitable for routine daily testing. Here we compared the performance of compact sequencing using the novel hybcell technology with 454 next-generation sequencing (454-NGS), Sanger sequencing, and pyrosequencing, using an evaluation panel of 35 specimens. A total of 32 mutations and 10 wild-type cases were reported using 454-NGS as the reference method. Specificity ranged from 100% for Sanger sequencing to 80% for pyrosequencing. Sanger sequencing and hybcell-based compact sequencing achieved a sensitivity of 96%, whereas pyrosequencing had a sensitivity of 88%. Accuracy was 97% for Sanger sequencing, 85% for pyrosequencing, and 94% for hybcell-based compact sequencing. Quantitative results were obtained for 454-NGS and hybcell-based compact sequencing data, resulting in a significant correlation (r = 0.914). Whereas pyrosequencing and Sanger sequencing were not able to detect multiple mutated cell clones within one tumor specimen, 454-NGS and the hybcell-based compact sequencing detected multiple mutations in two specimens. Our comparison shows that the hybcell-based compact sequencing is a valuable alternative to state-of-the-art methodologies used for detection of clinically relevant point mutations.

  11. 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.

  12. Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations.

    Directory of Open Access Journals (Sweden)

    Wenbin Li

    Full Text Available In sporadic colorectal cancer (CRC, the BRAFV600E mutation is associated with deficient mismatch repair (MMR status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+/pMMR (34.0%, KRAS (+/dMMR (2.9%, KRAS (-/pMMR (58.5% and KRAS (-/dMMR (4.6%. A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%, proximal located (45.5%, a mucinous histology (38.4%, and to have increased lymph node metastasis (60.3%, compared with pMMR tumors without BRAFV600E and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01. To the contrary, compared with those with KRAS(-/dMMR tumors, patients with KRAS(+/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers.

  13. 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

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

    International Nuclear Information System (INIS)

    Danilatos, Gerasimos; Kollia, Mary; Dracopoulos, Vassileios

    2015-01-01

    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

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

    Science.gov (United States)

    Danilatos, Gerasimos; Kollia, Mary; Dracopoulos, Vassileios

    2015-03-01

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 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.

  17. Detection of picosecond electrical transients in a scanning tunneling microscope

    NARCIS (Netherlands)

    Groeneveld, R.H.M.; Rasing, T.H.M.; Kaufmann, L.M.F.; Smalbrugge, E.; Wolter, J.H.; Melloch, M.R.; Kempen, van H.

    1996-01-01

    We have developed a scanning tunneling microscope using an optoelectronic switch which gates the tunneling tip current. The switch is fabricated within several tens of microns from the tip by photolithography and an accurate cleavage method. We demonstrate this approach by detecting picosecond

  18. Colorectal cancer detection by hyperspectral imaging using fluorescence excitation scanning

    Science.gov (United States)

    Leavesley, Silas J.; Deal, Joshua; Hill, Shante; Martin, Will A.; Lall, Malvika; Lopez, Carmen; Rider, Paul F.; Rich, Thomas C.; Boudreaux, Carole W.

    2018-02-01

    Hyperspectral imaging technologies have shown great promise for biomedical applications. These techniques have been especially useful for detection of molecular events and characterization of cell, tissue, and biomaterial composition. Unfortunately, hyperspectral imaging technologies have been slow to translate to clinical devices - likely due to increased cost and complexity of the technology as well as long acquisition times often required to sample a spectral image. We have demonstrated that hyperspectral imaging approaches which scan the fluorescence excitation spectrum can provide increased signal strength and faster imaging, compared to traditional emission-scanning approaches. We have also demonstrated that excitation-scanning approaches may be able to detect spectral differences between colonic adenomas and adenocarcinomas and normal mucosa in flash-frozen tissues. Here, we report feasibility results from using excitation-scanning hyperspectral imaging to screen pairs of fresh tumoral and nontumoral colorectal tissues. Tissues were imaged using a novel hyperspectral imaging fluorescence excitation scanning microscope, sampling a wavelength range of 360-550 nm, at 5 nm increments. Image data were corrected to achieve a NIST-traceable flat spectral response. Image data were then analyzed using a range of supervised and unsupervised classification approaches within ENVI software (Harris Geospatial Solutions). Supervised classification resulted in >99% accuracy for single-patient image data, but only 64% accuracy for multi-patient classification (n=9 to date), with the drop in accuracy due to increased false-positive detection rates. Hence, initial data indicate that this approach may be a viable detection approach, but that larger patient sample sizes need to be evaluated and the effects of inter-patient variability studied.

  19. Detecting damage in steel with scanning SQUID microscopy

    International Nuclear Information System (INIS)

    Lee, Tae-Kyu; Clatterbuck, D.M.; Morris, J.W. Jr.; Shaw, T.J.; Lee, Seungkyun; Clarke, John

    2002-01-01

    A 'Holy Grail' of NDE research is a non-destructive method for measuring fatigue damage prior to crack initiation. High-Tc scanning SQUID microscopy may be a useful tool. Because of the exceptional magnetic sensitivity of this technique, fatigue damage can be detected well before microcrack initiation, and in the absence of other obvious microstructure or property changes. Given the spatial resolution of the technique, undamaged material can be located and used to set internal standards

  20. Detecting damage in steel with scanning SQUID microscopy

    International Nuclear Information System (INIS)

    Lee, Tae-Kyu; Clatterbuck, David; Morris Jr., J.W.; Shaw, T.J.; McDermott R.; Clarke, John

    2001-01-01

    A ''Holy Grail'' of NDE research is a non-destructive method for measuring fatigue damage prior to crack initiation. High-Tc scanning SQUID microscopy may be a useful tool. Because of the exceptional magnetic sensitivity of this technique, fatigue damage can be detected well before microcrack initiation, and in the absence of other obvious microstructure or property changes. Given the spatial resolution of the technique, undamaged material can be located and used to set internal standards

  1. 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.

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

    KAUST Repository

    Hanafy, Sherif M.; Schuster, Gerard T.

    2014-01-01

    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.

  3. 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

    Colorectal cancer (CRC) is one of the most prevalent types of cancer, causing significant morbidity and mortality worldwide. CRC is curable if diagnosed at an early stage. Mutations in the oncogene KRAS play a critical role in early development of CRC. Detection of activated KRAS is of diagnostic...

  4. Minimum Detectable Activity for Tomographic Gamma Scanning System

    Energy Technology Data Exchange (ETDEWEB)

    Venkataraman, Ram [Canberra Industries (AREVA BDNM), Meriden, CT (United States); Smith, Susan [Canberra Industries (AREVA BDNM), Meriden, CT (United States); Kirkpatrick, J. M. [Canberra Industries (AREVA BDNM), Meriden, CT (United States); Croft, Stephen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    For any radiation measurement system, it is useful to explore and establish the detection limits and a minimum detectable activity (MDA) for the radionuclides of interest, even if the system is to be used at far higher values. The MDA serves as an important figure of merit, and often a system is optimized and configured so that it can meet the MDA requirements of a measurement campaign. The non-destructive assay (NDA) systems based on gamma ray analysis are no exception and well established conventions, such the Currie method, exist for estimating the detection limits and the MDA. However, the Tomographic Gamma Scanning (TGS) technique poses some challenges for the estimation of detection limits and MDAs. The TGS combines high resolution gamma ray spectrometry (HRGS) with low spatial resolution image reconstruction techniques. In non-imaging gamma ray based NDA techniques measured counts in a full energy peak can be used to estimate the activity of a radionuclide, independently of other counting trials. However, in the case of the TGS each “view” is a full spectral grab (each a counting trial), and each scan consists of 150 spectral grabs in the transmission and emission scans per vertical layer of the item. The set of views in a complete scan are then used to solve for the radionuclide activities on a voxel by voxel basis, over 16 layers of a 10x10 voxel grid. Thus, the raw count data are not independent trials any more, but rather constitute input to a matrix solution for the emission image values at the various locations inside the item volume used in the reconstruction. So, the validity of the methods used to estimate MDA for an imaging technique such as TGS warrant a close scrutiny, because the pair-counting concept of Currie is not directly applicable. One can also raise questions as to whether the TGS, along with other image reconstruction techniques which heavily intertwine data, is a suitable method if one expects to measure samples whose activities

  5. Clinical Relevance of KRAS in Human Cancers

    Directory of Open Access Journals (Sweden)

    Sylwia Jančík

    2010-01-01

    Full Text Available The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

  6. Contact detection for nanomanipulation in a scanning electron microscope

    International Nuclear Information System (INIS)

    Ru, Changhai; To, Steve

    2012-01-01

    Nanomanipulation systems require accurate knowledge of the end-effector position in all three spatial coordinates, XYZ, for reliable manipulation of nanostructures. Although the images acquired by a scanning electron microscope (SEM) provide high resolution XY information, the lack of depth information in the Z-direction makes 3D nanomanipulation time-consuming. Existing approaches for contact detection of end-effectors inside SEM typically utilize fragile touch sensors that are difficult to integrate into a nanomanipulation system. This paper presents a method for determining the contact between an end-effector and a target surface during nanomanipulation inside SEM, purely based on the processing of SEM images. A depth-from-focus method is used in the fast approach of the end-effector to the substrate, followed by fine contact detection. Experimental results demonstrate that the contact detection approach is capable of achieving an accuracy of 21.5 nm at 50,000× magnification while inducing little end-effector damage. -- Highlights: ► We presents a simple method for obtaining the depth information in SEM-based nanomanipulation. ► Detecting contact between an end-effector and a target surface using SEM as a vision sensor. ► Additional touch/force sensors or specialized hardware need not be added. ► Achieved high repeatability and accuracy. ► Complete automatic contact detection within typically 60 s.

  7. Contact detection for nanomanipulation in a scanning electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Changhai, E-mail: rchhai@gmail.com [Automation College, Harbin Engineering University, Harbin 150001 (China); Robotics and Microsystems Center, Soochow University, Jiangsu 215021 (China); To, Steve, E-mail: Steve.to@utoronto.ca [Department of Mechanical and Industry Engineering, University of Toronto, Ontario, Canada M5S3G8 (Canada)

    2012-07-15

    Nanomanipulation systems require accurate knowledge of the end-effector position in all three spatial coordinates, XYZ, for reliable manipulation of nanostructures. Although the images acquired by a scanning electron microscope (SEM) provide high resolution XY information, the lack of depth information in the Z-direction makes 3D nanomanipulation time-consuming. Existing approaches for contact detection of end-effectors inside SEM typically utilize fragile touch sensors that are difficult to integrate into a nanomanipulation system. This paper presents a method for determining the contact between an end-effector and a target surface during nanomanipulation inside SEM, purely based on the processing of SEM images. A depth-from-focus method is used in the fast approach of the end-effector to the substrate, followed by fine contact detection. Experimental results demonstrate that the contact detection approach is capable of achieving an accuracy of 21.5 nm at 50,000 Multiplication-Sign magnification while inducing little end-effector damage. -- Highlights: Black-Right-Pointing-Pointer We presents a simple method for obtaining the depth information in SEM-based nanomanipulation. Black-Right-Pointing-Pointer Detecting contact between an end-effector and a target surface using SEM as a vision sensor. Black-Right-Pointing-Pointer Additional touch/force sensors or specialized hardware need not be added. Black-Right-Pointing-Pointer Achieved high repeatability and accuracy. Black-Right-Pointing-Pointer Complete automatic contact detection within typically 60 s.

  8. Brazilian Amazonia Deforestation Detection Using Spatio-Temporal Scan Statistics

    Science.gov (United States)

    Vieira, C. A. O.; Santos, N. T.; Carneiro, A. P. S.; Balieiro, A. A. S.

    2012-07-01

    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 actives again; and finally

  9. 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

  10. 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.

  11. An Automated Road Roughness Detection from Mobile Laser Scanning Data

    Science.gov (United States)

    Kumar, P.; Angelats, E.

    2017-05-01

    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. The sensitivity of computed tomography (CT) scans in detecting trauma: are CT scans reliable enough for courtroom testimony?

    Science.gov (United States)

    Molina, D Kimberley; Nichols, Joanna J; Dimaio, Vincent J M

    2007-09-01

    Rapid and accurate recognition of traumatic injuries is extremely important in emergency room and surgical settings. Emergency departments depend on computed tomography (CT) scans to provide rapid, accurate injury assessment. We conducted an analysis of all traumatic deaths autopsied at the Bexar County Medical Examiner's Office in which perimortem medical imaging (CT scan) was performed to assess the reliability of the CT scan in detecting trauma with sufficient accuracy for courtroom testimony. Cases were included in the study if an autopsy was conducted, a CT scan was performed within 24 hours before death, and there was no surgical intervention. Analysis was performed to assess the correlation between the autopsy and CT scan results. Sensitivity, specificity, positive predictive value, and negative predictive value were defined for the CT scan based on the autopsy results. The sensitivity of the CT scan ranged from 0% for cerebral lacerations, cervical vertebral body fractures, cardiac injury, and hollow viscus injury to 75% for liver injury. This study reveals that CT scans are an inadequate detection tool for forensic pathologists, where a definitive diagnosis is required, because they have a low level of accuracy in detecting traumatic injuries. CT scans may be adequate for clinicians in the emergency room setting, but are inadequate for courtroom testimony. If the evidence of trauma is based solely on CT scan reports, there is a high possibility of erroneous accusations, indictments, and convictions.

  13. 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.

  14. Contact detection for nanomanipulation in a scanning electron microscope.

    Science.gov (United States)

    Ru, Changhai; To, Steve

    2012-07-01

    Nanomanipulation systems require accurate knowledge of the end-effector position in all three spatial coordinates, XYZ, for reliable manipulation of nanostructures. Although the images acquired by a scanning electron microscope (SEM) provide high resolution XY information, the lack of depth information in the Z-direction makes 3D nanomanipulation time-consuming. Existing approaches for contact detection of end-effectors inside SEM typically utilize fragile touch sensors that are difficult to integrate into a nanomanipulation system. This paper presents a method for determining the contact between an end-effector and a target surface during nanomanipulation inside SEM, purely based on the processing of SEM images. A depth-from-focus method is used in the fast approach of the end-effector to the substrate, followed by fine contact detection. Experimental results demonstrate that the contact detection approach is capable of achieving an accuracy of 21.5 nm at 50,000× magnification while inducing little end-effector damage. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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.

  16. Pedestrian Detection by Laser Scanning and Depth Imagery

    Science.gov (United States)

    Barsi, A.; Lovas, T.; Molnar, B.; Somogyi, A.; Igazvolgyi, Z.

    2016-06-01

    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).

  17. Colorectal cancer patients with low abundance of KRAS mutation may benefit from EGFR antibody therapy.

    Directory of Open Access Journals (Sweden)

    Shaorong Yu

    Full Text Available Epidermal growth factor receptor monoclonal antibody was approved for treatment of metastatic colorectal cancer patients carrying KRAS wild type DNA. However, recent studies showed that patients with KRAS G13D mutation may benefit from EGFR antibody therapy. In this study we tried to explore whether the abundance of KRAS mutation could affect the efficacy of EGFR antibody therapy. We firstly established a PNA-PCR method which could calculate the percentage of KRAS mutation in total DNA and proved its ability on 47 colorectal cancer samples bearing KRAS mutations. Then we analyzed the correlation between the abundance of KRAS mutations and efficacy of EGFR antibody therapy in another 35 metastatic colorectal cancer patients. We proved that PNA-PCR assay could calculate the abundance of KRAS mutation and the percentage of mutant DNA in tumor cells varied a lot (10.8%∼98.3% on the 47 colorectal cancer patients. The efficacy of EGFR antibody correlated with the abundance of KRAS mutations: in the KRAS mutation less than 30% group, the disease control rate was 44.4% (4/9; the disease control rate of 30∼80% group was 5.6% (1/18 and the >80% group was 12.5% (1/8 (P = 0.038. In summary, our study showed that PNA-PCR method could easily detect the percentage of KRAS mutation in tumor cells and colorectal cancer patients with low abundance of KRAS mutation might benefit from EGFR antibody therapy.

  18. 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.

  19. Substernal thyroid carcinoma detected by 67Ga scan in a patient with normal 131I scan

    International Nuclear Information System (INIS)

    Kim, e.E.; Maruyama, Y.; Deland, F.H.

    1978-01-01

    A patient with a superior mediastinal mass on an admission chest radiograph was initially evaluated by an 131 I thyroid scan which failed to demonstrate a substernal thyroid. However, the tomographic 67 Ga scan clearly showed an abnormal uptake in the area corresponding to the mass lesion on radiographic examination. Subsequent resection and biopsy of the substernal mass revealed a poorly differentiated follicular carcinoma with foci of anaplastic carcinoma. The differential diagnosis of the anterior mediastinal mass and the usefullness of the tomographic gallium scan are briefly discussed

  20. The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

    Science.gov (United States)

    Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

    2016-01-01

    Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

  1. Street-side vehicle detection, classification and change detection using mobile laser scanning data

    Science.gov (United States)

    Xiao, Wen; Vallet, Bruno; Schindler, Konrad; Paparoditis, Nicolas

    2016-04-01

    Statistics on street-side car parks, e.g. occupancy rates, parked vehicle types, parking durations, are of great importance for urban planning and policy making. Related studies, e.g. vehicle detection and classification, mostly focus on static images or video. Whereas mobile laser scanning (MLS) systems are increasingly utilized for urban street environment perception due to their direct 3D information acquisition, high accuracy and movability. In this paper, we design a complete system for car park monitoring, including vehicle recognition, localization, classification and change detection, from laser scanning point clouds. The experimental data are acquired by an MLS system using high frequency laser scanner which scans the streets vertically along the system's moving trajectory. The point clouds are firstly classified as ground, building façade, and street objects which are then segmented using state-of-the-art methods. Each segment is treated as an object hypothesis, and its geometric features are extracted. Moreover, a deformable vehicle model is fitted to each object. By fitting an explicit model to the vehicle points, detailed information, such as precise position and orientation, can be obtained. The model parameters are also treated as vehicle features. Together with the geometric features, they are applied to a supervised learning procedure for vehicle or non-vehicle recognition. The classes of detected vehicles are also investigated. Whether vehicles have changed across two datasets acquired at different times is detected to estimate the durations. Here, vehicles are trained pair-wisely. Two same or different vehicles are paired up as training samples. As a result, the vehicle recognition, classification and change detection accuracies are 95.9%, 86.0% and 98.7%, respectively. Vehicle modelling improves not only the recognition rate, but also the localization precision compared to bounding boxes.

  2. 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.

  3. 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

  4. Detection of Myocardial Infarcts by In-Vivo Scanning using Mercurascan

    Energy Technology Data Exchange (ETDEWEB)

    Vavrejn, B. [Research Institute for the Medical Use of Radioisotopes, Prague, Czechoslovak Socialist Republic (Czech Republic); Malek, P.; Kolc, J. [Institute for Clinical and Experimental Surgery, Prague, Czechoslovak Socialist Republic (Czech Republic); Ratusky, J. [Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague, Czechoslovak Socialist Republic (Czech Republic); Kronrad, L. [Institute for Nuclear Research, Rez near Prague, Czechoslovak Socialist Republic (Czech Republic)

    1969-05-15

    A method is described in which mercurascan (a hydroxymercury derivative of fluorescein) is injected intravenously into dogs before scanning so as to detect myocardial infarction as a 'hot' area on the scan. Experiments with some 150 dogs show that myocardial ischaemia could be demonstrated by in-vivo scanning within a short period of time after administration of mercurascan. (author)

  5. Fully automatic detection of corresponding anatomical landmarks in volume scans of different respiratory state

    International Nuclear Information System (INIS)

    Berlinger, Kajetan; Roth, Michael; Sauer, Otto; Vences, Lucia; Schweikard, Achim

    2006-01-01

    A method is described which provides fully automatic detection of corresponding anatomical landmarks in volume scans taken at different respiratory states. The resulting control points are needed for creating a volumetric deformation model for motion compensation in radiotherapy. Prior to treatment two CT volumes are taken, one scan during inhalation, one during exhalation. These scans and the detected control point pairs are taken as input for creating the four-dimensional model by using thin-plate splines

  6. 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

  7. 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 (cf......DNA) 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....... RESULTS: The study included 246 patients receiving a minimum of 1 treatment cycle, and all but four were evaluable for response according to RECIST. Forty-three patients (17.5%) presented with a KRAS mutation. OS was 8.9 months and PFS by intention to treat 5.4 months. Patients with a detectable plasma...

  8. Profilographic detection system for single-track scanning device

    International Nuclear Information System (INIS)

    Silar, J.; Kula, J.

    1988-01-01

    A profilographic detection system is claimed for diagnosing the renal function by isotope nephrography, and the bladder filling in small children and infants. The configuration described guarantees good position resolution and sensitivity of the detection system. (E.J.). 2 figs

  9. Detection of intracavitary masses on gated scans: a phantom study

    International Nuclear Information System (INIS)

    Cho, B.; Yasuda, Tsunehiro; Moore, R.H.; Boucher, C.A.; Strauss, H.W.

    1987-01-01

    A series of 1.5, 2.0 and 3.0 cm diameter paraffin balls were placed on a 3 cm tether within a simulated left ventricular balloon phantom to determine the maximal balloon volume that permitted identification of the lesion. When images were recorded with the phantom stationary, the lesions could be detected at 100, 280 and 360 ml volumes, respectively. When the phantom was set in motion with a fixed 80 ml stroke volume, the lesions were detected at 120, 320 and 360 ml, respectively. These findings suggest that gating does not decrease lesion detection even when the lesion is freely mobile, and a 1.5 cm lesion would be difficult to detect in an enlarged ventricle, but 2 and 3 cm lesions could be detected even in the presence of moderate ventricular enlargement. (author)

  10. Detection of irradiated food by differential scanning calorimetry

    International Nuclear Information System (INIS)

    Nesvadba, P.; Kent, M.

    1991-01-01

    It has been showed that the freezing point of chicken is depressed on irradiation and that this can serve as a possible method of detection of irradiated chicken. The purposed of the present work was to see whether other foods (cod, mushroom) show the freezing point depression

  11. Localization of active, dually phosphorylated extracellular signal-regulated kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS mutations

    DEFF Research Database (Denmark)

    Holck, Susanne; Bonde, Jesper; Pedersen, Helle

    2016-01-01

    Colorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate the extracellular signal-regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis. However, immunohistochemical results on ERK activation in such tumors differ...... detectable increases in phosphorylation of ERK (pERK), we stained biopsies from 36 CRC patients with activating mutations in the BRAF gene (BRAFV600E: BRAF(m)), the KRAS gene (KRAS(m)) or in neither (BRAF/KRAS(n)) with this optimized method. Staining was scored in blind-coded specimens by two observers....... Staining of stromal cells was used as a positive control. BRAF(m) or KRAS(m) tumors did not show higher staining scores than BRAF/KRAS(n) tumors. Although BRAFV600E staining occurred in over 90% of cancer cells in all 9 BRAF(m) tumors, 3 only showed staining for pERK in less than 10% of cancer cell nuclei...

  12. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

    International Nuclear Information System (INIS)

    Sánchez-Muñoz, Alfonso; Gallego, Elena; Luque, Vanessa de; Pérez-Rivas, Luís G; Vicioso, Luís; Ribelles, Nuria; Lozano, José; Alba, Emilio

    2010-01-01

    Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. We found no evidence of KRAS oncogenic mutations in all analyzed tumors. This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases

  13. Detection of Recurrent Cervical Cancer by Whole-body FDG PET Scans

    Institute of Scientific and Technical Information of China (English)

    Jiaxin Yang; Jinhui Wang; Zhaohui Zhu; Keng Shen; Bocheng Wang

    2008-01-01

    OBJECTIVE To evaluate the role of whole-body {18F} fluro-2-dexoxyglucose (FDG) positron emission tomography (PET) scans in the detection of recurrent cervical cancer.METHODS Between June, 2000 and January, 2006, 25 patients had undergone a PET scan at the Peking Union Medical College Hospital to evaluate possible recurrent cervical cancer. All the PET findings were reviewed and compared to available clinical data to classify each PET scan result as a true positive, true negative, false positive, or false negative.RESULTS A total of 38 PET scans were conducted on the 25patients whose median age was 46 years. The Stage distributions were IA (n = 1), IB (n = 11), IIA (n = 5), IIB (n = 4), IIIB (n = 2), WB (n= 1), and unknown Stage (n = 1). There were 22 cases of squamous cell carcinoma and 3 cases of adenocarcinoma resulting in 9 true positive PET scans, 27 true negatives, 2 false positives and no false negatives. The sensitivity of the FDG PET scans for detecting recurrent cervical cancer was 100%, specificity 93.1%, positive predictive value 81.8%, and negative predictive value 100%.CONCLUSION The whole body FDG PET scans are a sensitive and specific imaging modality for the detection of recurrent cervical cancer. However the cost of PET scans is too high at this time. A large prospective study will determine whether this modality should be used routinely and take the place of other imaging methods in the early detection of recurrent cervical carcinoma

  14. Fluorescence in situ hybridization on human metaphase chromosomes detected by near-field scanning optical microscopy

    NARCIS (Netherlands)

    Moers, M.H.P.; Moers, M.H.P.; Kalle, W.H.J.; Kalle, W.H.J.; Ruiter, A.G.T.; Wiegant, J.C.A.G.; Raap, A.K.; Greve, Jan; de Grooth, B.G.; van Hulst, N.F.

    1996-01-01

    Fluorescence in situ hybridization o­n human metaphase chromosomes is detected by near-field scanning optical microscopy. This combination of cytochemical and scanning probe techniques enables the localization and identification of several fluorescently labelled genomic DNA fragments o­n a single

  15. A flexible spatial scan statistic with a restricted likelihood ratio for detecting disease clusters.

    Science.gov (United States)

    Tango, Toshiro; Takahashi, Kunihiko

    2012-12-30

    Spatial scan statistics are widely used tools for detection of disease clusters. Especially, the circular spatial scan statistic proposed by Kulldorff (1997) has been utilized in a wide variety of epidemiological studies and disease surveillance. However, as it cannot detect noncircular, irregularly shaped clusters, many authors have proposed different spatial scan statistics, including the elliptic version of Kulldorff's scan statistic. The flexible spatial scan statistic proposed by Tango and Takahashi (2005) has also been used for detecting irregularly shaped clusters. However, this method sets a feasible limitation of a maximum of 30 nearest neighbors for searching candidate clusters because of heavy computational load. In this paper, we show a flexible spatial scan statistic implemented with a restricted likelihood ratio proposed by Tango (2008) to (1) eliminate the limitation of 30 nearest neighbors and (2) to have surprisingly much less computational time than the original flexible spatial scan statistic. As a side effect, it is shown to be able to detect clusters with any shape reasonably well as the relative risk of the cluster becomes large via Monte Carlo simulation. We illustrate the proposed spatial scan statistic with data on mortality from cerebrovascular disease in the Tokyo Metropolitan area, Japan. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Arterial scan versus radiographic angiography in detection of shallow arterial ulcers

    International Nuclear Information System (INIS)

    Pollak, E.W.; Webber, M.M.; Cragin, M.D.; Wolfman, E.F. Jr.

    1977-01-01

    A comparison of 99m-technetium albumin aggregated arterial scan and radiographic angiography for detection of shallow intimal carotid artery ulcerations was made in a series of 12 anesthetized dogs, having a total of 16 acute arterial ulcerations. Radiographic angiography showed positive findings related to presence of stenosis or mural thrombosis in 12 instances. Direct visualization of ulceration was only exceptionally encountered. Arterial scan detected 14 of 16 intimal ulcers. The radionuclide method was reliable even in absence of stenosis or when only minimal mural thrombosis was present. Moreover, autopsy scan of the isolated arterial segments detected all 16 intimal lesions. These results indicate that the arterial scan was a more reliable method for detection of shallow arterial ulcers in this experimental model than radiographic angiography, especially when arterial lumen stenosis or mural thrombosis was minimal or absent

  17. Usefulness of thin slice target CT scan in detecting mediastinal and hilar lymphadenopathy

    International Nuclear Information System (INIS)

    Yoshida, Shoji; Maeda, Tomoho; Nishioka, Masatoshi

    1986-01-01

    Comparative study of target scan with the different slice thickness and scan modes was performed to evaluate the mediastinal and hilar lymphadenopathy. 20 cases in controls and 35 cases in lymphadenopathy were examined. To delineate mediastinal and hilar lymphadenopathy, the scan mode of standard target was most useful in contrast and sharpness. Thin slice thickness with 5 mm was necessary in detecting small lymphnode or contour and internal structure of enlarged lymphnode. Valuable estimation of 5 mm contiguous target scan was obtained in the subaortic node (no. 5), tracheobronchial node (no. 4), precarinal and subcarinal node (no. 7) and right hilar node (no. 12). (author)

  18. Multiple Hotspot Mutations Scanning by Single Droplet Digital PCR.

    Science.gov (United States)

    Decraene, Charles; Silveira, Amanda B; Bidard, François-Clément; Vallée, Audrey; Michel, Marc; Melaabi, Samia; Vincent-Salomon, Anne; Saliou, Adrien; Houy, Alexandre; Milder, Maud; Lantz, Olivier; Ychou, Marc; Denis, Marc G; Pierga, Jean-Yves; Stern, Marc-Henri; Proudhon, Charlotte

    2018-02-01

    Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan ® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. The KRAS and EGFR assays were highly specific and both reached a limit of detection of <0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy. © 2017 American Association for Clinical Chemistry.

  19. Dual-detection confocal fluorescence microscopy: fluorescence axial imaging without axial scanning.

    Science.gov (United States)

    Lee, Dong-Ryoung; Kim, Young-Duk; Gweon, Dae-Gab; Yoo, Hongki

    2013-07-29

    We propose a new method for high-speed, three-dimensional (3-D) fluorescence imaging, which we refer to as dual-detection confocal fluorescence microscopy (DDCFM). In contrast to conventional beam-scanning confocal fluorescence microscopy, where the focal spot must be scanned either optically or mechanically over a sample volume to reconstruct a 3-D image, DDCFM can obtain the depth of a fluorescent emitter without depth scanning. DDCFM comprises two photodetectors, each with a pinhole of different size, in the confocal detection system. Axial information on fluorescent emitters can be measured by the axial response curve through the ratio of intensity signals. DDCFM can rapidly acquire a 3-D fluorescent image from a single two-dimensional scan with less phototoxicity and photobleaching than confocal fluorescence microscopy because no mechanical depth scans are needed. We demonstrated the feasibility of the proposed method by phantom studies.

  20. Gamma scan technique for detecting coupon inside the mother pipeline

    International Nuclear Information System (INIS)

    Rasif Mohd Zain; Roslan Yahya; Mohamad Rabaie Shari; Airwan Affandi Mahmood; Mior Ahmad Khusaini Adnan

    2012-01-01

    Many times a year natural gas transmission and distribution companies need to make new connections to pipelines to expand or modify their existing system through hot tapping procedure. This procedure involves the installation of a new pipeline connection while the pipeline remains in service, flowing natural gas under pressure. The hot tap procedure includes attaching a branch connection and valve on the outside of an operating pipeline, and then cutting out the pipe-line wall within the branch and removing the wall section, which is called object of coupon through the valve. During the hot tapping process a critical problems occurred when a coupon fell into the mother pipeline. To overcome this problem, a gamma-ray absorption technique was chosen whereby a mapping technique will be done to detect the coupon position. The technique is non-destructive as it applies Co-60 (5 mCi) as a radioisotope sealed source to emit gamma radiation and a NaI(Tl) scintillation as detector. The result provided a visible representation of density profile inside pipeline where the coupon location can be located. This paper provides the detail of the technique used and presents the result obtained. (author)

  1. 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.

  2. Long-term follow-up of patients with a clinically benign extrahepatic biliary stenosis and K-ras mutation in endobiliary brush cytology

    NARCIS (Netherlands)

    van Heek, N. Tjarda; Rauws, Erik A. J.; Caspers, Eric; Drillenburg, Paul; Gouma, Dirk J.; Offerhaus, G. Johan A.

    2002-01-01

    Background. K-ras mutations in endobiliary brush cytology are an early event in carcinogenesis and justify a suspicion of malignancy in patients with extrahepatic biliary stenosis. However, K-ras mutations have been detected in specimens obtained by brushing of clinically benign extrahepatic biliary

  3. 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.

  4. Use of rapid-scan EPR to improve detection sensitivity for spin-trapped radicals.

    Science.gov (United States)

    Mitchell, Deborah G; Rosen, Gerald M; Tseitlin, Mark; Symmes, Breanna; Eaton, Sandra S; Eaton, Gareth R

    2013-07-16

    The short lifetime of superoxide and the low rates of formation expected in vivo make detection by standard continuous wave (CW) electron paramagnetic resonance (EPR) challenging. The new rapid-scan EPR method offers improved sensitivity for these types of samples. In rapid-scan EPR, the magnetic field is scanned through resonance in a time that is short relative to electron spin relaxation times, and data are processed to obtain the absorption spectrum. To validate the application of rapid-scan EPR to spin trapping, superoxide was generated by the reaction of xanthine oxidase and hypoxanthine with rates of 0.1-6.0 μM/min and trapped with 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO). Spin trapping with BMPO to form the BMPO-OOH adduct converts the very short-lived superoxide radical into a more stable spin adduct. There is good agreement between the hyperfine splitting parameters obtained for BMPO-OOH by CW and rapid-scan EPR. For the same signal acquisition time, the signal/noise ratio is >40 times higher for rapid-scan than for CW EPR. Rapid-scan EPR can detect superoxide produced by Enterococcus faecalis at rates that are too low for detection by CW EPR. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. 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

  7. Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

    Science.gov (United States)

    Abbas, A; Smith, A; Cecelja, M; Waltham, M

    2012-02-01

    AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  8. Molecular analysis of p53 and K-ras in lung carcinomas of coal miners

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, F.H.; Li, Y.W.; Vallyathan, V. [Wayne State University, Detroit, MI (United States). School of Medicine, Dept. of Pathology

    2001-10-01

    Thirty-three cases of non-small cell lung cancers (NSCLC) from the archives of National Coal Workers' Autopsy Study were studied for mutational alterations in p53 and K-ras using PCR-SSCP, DNA sequencing and PCR-oligonucleotide probe hybridization techniques. Mutations of the p53 were observed in 4 smokers (19%) and one in a never smoker (8%). Two polymorphisms in smokers were detected at codon 213, a common site for sequence variation. Among the smokers the p53 mutations were in the heavy smokers. In never smokers there was only a single p53 mutation and two K-ras mutations. In never smokers the frequency of K-ras mutations was similar (17%) in smokers, but one never smoker had two K-ras mutations. Mutations of p53 were more frequent in adenocarcinomas (27%) and they were AT-GC transitions. There were two large cell undifferentiated carcinomas with p53 mutation and one with a K-ras mutation. Two of the 16 squamous cell carcinomas were positive for p53 mutation, while no K-ras mutations were found in this group. The results of these preliminary studies indicate a moderately different mutational spectrum of p53 and K-ras in coal miners independent of cigarette smoking. The mutational spectrum observed in this study of coal miners with heavy cigarette smoking history suggest a protective effect of coal mine dust in preventing abnormal mutations induced by chemical carcinogens in cigarette smoke or reactive oxygen species.

  9. Detection of attack-targeted scans from the Apache HTTP Server access logs

    Directory of Open Access Journals (Sweden)

    Merve Baş Seyyar

    2018-01-01

    Full Text Available A web application could be visited for different purposes. It is possible for a web site to be visited by a regular user as a normal (natural visit, to be viewed by crawlers, bots, spiders, etc. for indexing purposes, lastly to be exploratory scanned by malicious users prior to an attack. An attack targeted web scan can be viewed as a phase of a potential attack and can lead to more attack detection as compared to traditional detection methods. In this work, we propose a method to detect attack-oriented scans and to distinguish them from other types of visits. In this context, we use access log files of Apache (or ISS web servers and try to determine attack situations through examination of the past data. In addition to web scan detections, we insert a rule set to detect SQL Injection and XSS attacks. Our approach has been applied on sample data sets and results have been analyzed in terms of performance measures to compare our method and other commonly used detection techniques. Furthermore, various tests have been made on log samples from real systems. Lastly, several suggestions about further development have been also discussed.

  10. Penalized likelihood and multi-objective spatial scans for the detection and inference of irregular clusters

    Directory of Open Access Journals (Sweden)

    Fonseca Carlos M

    2010-10-01

    detection of moderately irregularly shaped clusters. The multi-objective cohesion scan is most effective for the detection of highly irregularly shaped clusters.

  11. Automatic detection of axillary lymphadenopathy on CT scans of untreated chronic lymphocytic leukemia patients

    Science.gov (United States)

    Liu, Jiamin; Hua, Jeremy; Chellappa, Vivek; Petrick, Nicholas; Sahiner, Berkman; Farooqui, Mohammed; Marti, Gerald; Wiestner, Adrian; Summers, Ronald M.

    2012-03-01

    Patients with chronic lymphocytic leukemia (CLL) have an increased frequency of axillary lymphadenopathy. Pretreatment CT scans can be used to upstage patients at the time of presentation and post-treatment CT scans can reduce the number of complete responses. In the current clinical workflow, the detection and diagnosis of lymph nodes is usually performed manually by examining all slices of CT images, which can be time consuming and highly dependent on the observer's experience. A system for automatic lymph node detection and measurement is desired. We propose a computer aided detection (CAD) system for axillary lymph nodes on CT scans in CLL patients. The lung is first automatically segmented and the patient's body in lung region is extracted to set the search region for lymph nodes. Multi-scale Hessian based blob detection is then applied to detect potential lymph nodes within the search region. Next, the detected potential candidates are segmented by fast level set method. Finally, features are calculated from the segmented candidates and support vector machine (SVM) classification is utilized for false positive reduction. Two blobness features, Frangi's and Li's, are tested and their free-response receiver operating characteristic (FROC) curves are generated to assess system performance. We applied our detection system to 12 patients with 168 axillary lymph nodes measuring greater than 10 mm. All lymph nodes are manually labeled as ground truth. The system achieved sensitivities of 81% and 85% at 2 false positives per patient for Frangi's and Li's blobness, respectively.

  12. Three phase bone scan , Ga-67 and Tc-99m nanocoll scan in detection of osteomyelitis caused by war injuries

    International Nuclear Information System (INIS)

    Banek, T.; Reljica-Kostic, Z.; Kurnik, G.

    1994-01-01

    Thirty three injured soldiers were surgically treated because of pierce wounds of extremities. Treatment was either osteosynthesis or external fixation. Two to four weeks post treatment clinical signs of osteomyelitis appeared. X-ray was negative in all patients. Three-phase bone scan was performed in order to establish diagnosis. Bone scan was positive in all patients. For 11 patients only bone scan was sufficient for decision of further treatment. In 22 patients Ga-67 or Tc-99m- nanocoll or both examinations were performed on surgeon's request. In 2 patients out of 5 with additional Ga-67 scan, Ga-67 scan showed more lesions than it was seen on bone scan. In 3 patients out of 5 with additional Tc-99m-nanocoll scan, Tc-99m-nanocoll scan showed more lesions than it was seen on bone scan. In 12 patients with positive bone scan and negative or unclear Ga-67, Tc-99m-nanocoll scan was performed. In 5 out of 12 patients Tc-99m- nanocoll scan established diagnosis in others confirmed finding on bone and Ga-67 scan. Our results showed that in one third of our causes bone scan was sufficient for diagnosing of osteomyelitis caused by war injuries. In selected cases where bone scan was not sufficient for diagnosis and decision for treatment Tc-99m-nanocoll was more sensitive than Ga-67. In our experience three-phase bone scan is more sensitive than Ga-67. In our opinion three-phase bone scan is the method of choice for diagnosing osteomyelitis in war situation with a lot of casualties. (author)

  13. 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.

  14. 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.

  15. Automated detection of analyzable metaphase chromosome cells depicted on scanned digital microscopic images

    Science.gov (United States)

    Qiu, Yuchen; Wang, Xingwei; Chen, Xiaodong; Li, Yuhua; Liu, Hong; Li, Shibo; Zheng, Bin

    2010-02-01

    Visually searching for analyzable metaphase chromosome cells under microscopes is quite time-consuming and difficult. To improve detection efficiency, consistency, and diagnostic accuracy, an automated microscopic image scanning system was developed and tested to directly acquire digital images with sufficient spatial resolution for clinical diagnosis. A computer-aided detection (CAD) scheme was also developed and integrated into the image scanning system to search for and detect the regions of interest (ROI) that contain analyzable metaphase chromosome cells in the large volume of scanned images acquired from one specimen. Thus, the cytogeneticists only need to observe and interpret the limited number of ROIs. In this study, the high-resolution microscopic image scanning and CAD performance was investigated and evaluated using nine sets of images scanned from either bone marrow (three) or blood (six) specimens for diagnosis of leukemia. The automated CAD-selection results were compared with the visual selection. In the experiment, the cytogeneticists first visually searched for the analyzable metaphase chromosome cells from specimens under microscopes. The specimens were also automated scanned and followed by applying the CAD scheme to detect and save ROIs containing analyzable cells while deleting the others. The automated selected ROIs were then examined by a panel of three cytogeneticists. From the scanned images, CAD selected more analyzable cells than initially visual examinations of the cytogeneticists in both blood and bone marrow specimens. In general, CAD had higher performance in analyzing blood specimens. Even in three bone marrow specimens, CAD selected 50, 22, 9 ROIs, respectively. Except matching with the initially visual selection of 9, 7, and 5 analyzable cells in these three specimens, the cytogeneticists also selected 41, 15 and 4 new analyzable cells, which were missed in initially visual searching. This experiment showed the feasibility of

  16. Frequency-scanning MALDI linear ion trap mass spectrometer for large biomolecular ion detection.

    Science.gov (United States)

    Lu, I-Chung; Lin, Jung Lee; Lai, Szu-Hsueh; Chen, Chung-Hsuan

    2011-11-01

    This study presents the first report on the development of a matrix-assisted laser desorption ionization (MALDI) linear ion trap mass spectrometer for large biomolecular ion detection by frequency scan. We designed, installed, and tested this radio frequency (RF) scan linear ion trap mass spectrometer and its associated electronics to dramatically extend the mass region to be detected. The RF circuit can be adjusted from 300 to 10 kHz with a set of operation amplifiers. To trap the ions produced by MALDI, a high pressure of helium buffer gas was employed to quench extra kinetic energy of the heavy ions produced by MALDI. The successful detection of the singly charged secretory immunoglobulin A ions indicates that the detectable mass-to-charge ratio (m/z) of this system can reach ~385 000 or beyond.

  17. 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.

  18. Nodule detection methods using autocorrelation features on 3D chest CT scans

    International Nuclear Information System (INIS)

    Hara, T.; Zhou, X.; Okura, S.; Fujita, H.; Kiryu, T.; Hoshi, H.

    2007-01-01

    Lung cancer screening using low dose X-ray CT scan has been an acceptable examination to detect cancers at early stage. We have been developing an automated detection scheme for lung nodules on CT scan by using second-order autocorrelation features and the initial performance for small nodules (< 10 mm) shows a high true-positive rate with less than four false-positive marks per case. In this study, an open database of lung images, LIDC (Lung Image Database Consortium), was employed to evaluate our detection scheme as an consistency test. The detection performance for solid and solitary nodules in LIDC, included in the first data set opened by the consortium, was 83% (10/12) true-positive rate with 3.3 false-positive marks per case. (orig.)

  19. Automated detection of delamination and disbond from wavefield images obtained using a scanning laser vibrometer

    International Nuclear Information System (INIS)

    Sohn, H; Yang, J Y; Dutta, D; DeSimio, M; Olson, S; Swenson, E

    2011-01-01

    The paper presents signal and image processing algorithms to automatically detect delamination and disbond in composite plates from wavefield images obtained using a scanning laser Doppler vibrometer (LDV). Lamb waves are excited by a lead zirconate titanate transducer (PZT) mounted on the surface of a composite plate, and the out-of-plane velocity field is measured using an LDV. From the scanned time signals, wavefield images are constructed and processed to study the interaction of Lamb waves with hidden delaminations and disbonds. In particular, the frequency–wavenumber (f–k) domain filter and the Laplacian image filter are used to enhance the visibility of defects in the scanned images. Thereafter, a statistical cluster detection algorithm is used to identify the defect location and distinguish damaged specimens from undamaged ones

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

    International Nuclear Information System (INIS)

    Caicedo, Carlos; Garcia-Velloso, Maria Jose; Vigil Diaz, Carmen; Richter Echevarria, Jose Angel; Lozano, Maria Dolores; Labiano, Tania; Lopez-Picazo, Jose Maria; Gurpide, Alfonso; Perez Gracia, Jose Luis; Zulueta, Javier

    2014-01-01

    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 [ 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 [ 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 [ 18 F]FDG PET/CT for predicting KRAS mutation. From 102 patients staged using [ 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 [ 18 F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p 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 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.)

  1. 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, beca...

  2. Detection of vertical root fractures in endodontically treated teeth by a cone beam computed tomography scan

    NARCIS (Netherlands)

    Hassan, B.; Metska, M.E.; Özok, A.R.; van der Stelt, P.; Wesselink, P.R.

    2009-01-01

    Our aim was to compare the accuracy of cone beam computed tomography (CBCT) scans and periapical radiographs (PRs) in detecting vertical root fractures (VRFs) and to assess the influence of root canal filling (RCF) on fracture visibility. Eighty teeth were endodontically prepared and divided into

  3. Computer-Aided Detection of Kidney Tumor on Abdominal Computed Tomography Scans

    International Nuclear Information System (INIS)

    Kim, D.Y.; Park, J.W.

    2004-01-01

    Purpose: To implement a computer-aided detection system for kidney segmentation and kidney tumor detection on abdominal computed tomography (CT) scans. Material and Methods: Abdominal CT images were digitized with a film digitizer, and a gray-level threshold method was used to segment the kidney. Based on texture analysis performed on sample images of kidney tumors, a portion of the kidney tumor was selected as seed region for start point of the region-growing process. The average and standard deviations were used to detect the kidney tumor. Starting at the detected seed region, the region-growing method was used to segment the kidney tumor with intensity values used as an acceptance criterion for a homogeneous test. This test was performed to merge the neighboring region as kidney tumor boundary. These methods were applied on 156 transverse images of 12 cases of kidney tumors scanned using a G.E. Hispeed CT scanner and digitized with a Lumisys LS-40 film digitizer. Results: The computer-aided detection system resulted in a kidney tumor detection sensitivity of 85% and no false-positive findings. Conclusion: This computer-aided detection scheme was useful for kidney tumor detection and gave the characteristics of detected kidney tumors

  4. Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

    Science.gov (United States)

    Perets, Ruth; Greenberg, Orli; Shentzer, Talia; Semenisty, Valeria; Epelbaum, Ron; Bick, Tova; Sarji, Shada; Ben-Izhak, Ofer; Sabo, Edmond; Hershkovitz, Dov

    2018-05-01

    Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an efficient ctDNA marker for PDAC monitoring. Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival. Plasma KRAS mutations were detected in 5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival. Our results confirm that mutant KRAS ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring. Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers

  5. The proto-oncogene KRAS and BRAF profiles and some clinical characteristics in colorectal cancer in the Turkish population.

    Science.gov (United States)

    Ozen, Filiz; Ozdemir, Semra; Zemheri, Ebru; Hacimuto, Gizem; Silan, Fatma; Ozdemir, Ozturk

    2013-02-01

    The aim of the current study was to investigate the prevalence and predictive significance of the KRAS and BRAF mutations in Turkish patients with colorectal cancer (CRC). Totally, 53 fresh tumoral tissue specimens were investigated in patients with CRC. All specimens were obtained during routine surgery of patients who were histopathologically diagnosed and genotyped for common KRAS and BRAF point mutations. After DNA extraction, the target mutations were analyzed using the AutoGenomics INFINITI(®) assay, and some samples were confirmed by quantitative real-time polymerase chain reaction fluorescence melting curve analyses. KRAS mutations were found in 26 (49.05%) CRC samples. Twenty-seven samples (50.95%) had wild-type profiles for KRAS codon 12, 13, and 61 in the current cohort. In 17 (65.38%) samples, codon 12; in 7 (26.93%) samples, codon 13; and in 2 (7.69%) samples, codon 61 were found to be mutated, particularly in grade 2 of tumoral tissues. No point mutation was detected in BRAF codon Val600Glu for the studied CRC patients. Our study, based on a representative collection of human CRC tumors, indicates that KRAS gene mutations were detected in 49.05% of the samples, and the most frequent mutation was in the G12D codon. Results also showed that codons 12 and 13 of KRAS are relatively frequently without BRAF mutation in a CRC cohort from the Turkish population.

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

    African Journals Online (AJOL)

    We studied retrospectively tumor samples of 83 Saudi metastatic CRC patients for KRAS mutations in codon 12 and codon 13, to evaluate the relevance of KRAS mutation positive colorectal cancers with metastatic sites. KRAS mutation was observed in 42.2% (35/83) patients with CRC. The most common mutations were in ...

  7. Genetic analysis of tumorigenesis: XXXII. Localization of constitutionally amplified KRAS sequences to Chinese hamster chromosomes X and Y by in situ hybridization.

    Science.gov (United States)

    Stenman, G; Anisowicz, A; Sager, R

    1988-11-01

    The KRAS gene is constitutionally amplified in the Chinese hamster. We have mapped the amplified sequences by in situ hybridization to two major sites on the X and Y chromosomes, Xq4 and Yp2. No autosomal site was detected despite a search under relaxed hybridization conditions. KRAS DNA is amplified about 50-fold compared to a human cell line known to have a diploid number of KRAS sequences, whereas mRNA expression is 5- to 10-fold lower than in normal human cells. While mRNA expression levels do not necessarily parallel gene copy number, the low expression level strongly suggests that the amplified sequences are transcriptionally silent. It is suggested that the amplified sequences arose from the original KRAS gene on chromosome 8 and that the KRAS sequences on the Y chromosome arose by X-Y recombination.

  8. Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Davies, Janine M; Trembath, Dimitri; Deal, Allison M; Funkhouser, William K; Calvo, Benjamin F; Finnegan, Timothy; Weck, Karen E; Tepper, Joel E; O'Neil, Bert H

    2011-01-01

    KRAS mutations may predict poor response to radiotherapy. Downstream events from KRAS, such as activation of BRAF, AKT and ERK, may also confer prognostic information but have not been tested in rectal cancer (RC). Our objective was to explore the relationships of KRAS and BRAF mutation status with p-AKT and p-ERK and outcomes in RC. Pre-radiotherapy RC tumor biopsies were evaluated. KRAS and BRAF mutations were assessed by pyrosequencing; p-AKT and p-ERK expression by immunohistochemistry. Of 70 patients, mean age was 58; 36% stage II, 56% stage III, and 9% stage IV. Responses to neoadjuvant chemoradiotherapy: 64% limited, 19% major, and 17% pathologic complete response. 64% were KRAS WT, 95% were BRAF WT. High p-ERK levels were associated with improved OS but not for p-AKT. High levels of p-AKT and p-ERK expression were associated with better responses. KRAS WT correlated with lower p-AKT expression but not p-ERK expression. No differences in OS, residual disease, or tumor downstaging were detected by KRAS status. KRAS mutation was not associated with lesser response to chemoradiotherapy or worse OS. High p-ERK expression was associated with better OS and response. Higher p-AKT expression was correlated with better response but not OS

  9. 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.

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

    OpenAIRE

    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 accur...

  11. Ultrasonography and indium 111 white blood cell scanning for the detection of intraabdominal abscesses

    International Nuclear Information System (INIS)

    Carroll, B.; Silverman, P.M.; Goodwin, D.A.; McDougall, I.R.

    1981-01-01

    Ultrasound and indium 111 white blood cell scanning were performed on 163 patients with suspected intraabdominal abscesses. In all but one case, intraabdominal abscesses were correctly identified by one or both tests; conversely, no patient was falsely diagnosed by both tests to have an abscess. Sonography was useful in those patients with focal symptoms, and frequently identified nonabscess causes for fever. White cell scanning was valuable when focal signs were absent, and frequently identified extraabdominal sources of sepsis. The two imaging modalities are complementary and provide a highly accurate and sensitive means of intraabdominal abscess detection

  12. 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.

  13. 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.

  14. Using Information From Prior Satellite Scans to Improve Cloud Detection Near the Day-Night Terminator

    Science.gov (United States)

    Yost, Christopher R.; Minnis, Patrick; Trepte, Qing Z.; Palikonda, Rabindra; Ayers, Jeffrey K.; Spangenberg, Doulas A.

    2012-01-01

    With geostationary satellite data it is possible to have a continuous record of diurnal cycles of cloud properties for a large portion of the globe. Daytime cloud property retrieval algorithms are typically superior to nighttime algorithms because daytime methods utilize measurements of reflected solar radiation. However, reflected solar radiation is difficult to accurately model for high solar zenith angles where the amount of incident radiation is small. Clear and cloudy scenes can exhibit very small differences in reflected radiation and threshold-based cloud detection methods have more difficulty setting the proper thresholds for accurate cloud detection. Because top-of-atmosphere radiances are typically more accurately modeled outside the terminator region, information from previous scans can help guide cloud detection near the terminator. This paper presents an algorithm that uses cloud fraction and clear and cloudy infrared brightness temperatures from previous satellite scan times to improve the performance of a threshold-based cloud mask near the terminator. Comparisons of daytime, nighttime, and terminator cloud fraction derived from Geostationary Operational Environmental Satellite (GOES) radiance measurements show that the algorithm greatly reduces the number of false cloud detections and smoothes the transition from the daytime to the nighttime clod detection algorithm. Comparisons with the Geoscience Laser Altimeter System (GLAS) data show that using this algorithm decreases the number of false detections by approximately 20 percentage points.

  15. Case of multiple hepatic abscesses detected by CT scan in the patient with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Saburi, Yoshio; Shuto, Ryusuke; Mizutani, Ryoko; Hosokawa, Takafumi; Itoga, Takashi (Medical Coll. of Oita (Japan))

    1983-12-01

    A 34 year old man admitted to a hospital on 21 Feb. 1983 was diagnosed acute lymphoblastic leukemia. A hematological complete remission was achieved by combination therapy of vincristine, prednisolone and L-asparaginase. However, he had been complaining of high fever and right hypochondralgia since early in Apr. 1983, and it was revealed that elevation of right diaphragm on chest X-ray. Therefore, he was also given several antibiotics (CPZ, TOB, LMOX, PIPC, LCM, AMK, MINO and GM) for complication of probable liver abscess. Remittent fever persisted in spite of as mentioned above various antibiotics. The multiple hepatic abscesses were found by CT scan of the mid-abdomen as the low density lesions, but bacterial cultures detected no pathogens. His complaining of remittent fever and right hypochondralgia were improved by treatment with Miconazole during about one month, and decreasing in size and number of multiple hepatic abscesses were found by CT scan. Though we could not determine clearly, but suspected that multiple hepatic abscesses were due to fungus infection, by reason of therapeutic result. Regarding the complication of hepatic abscesses with leukemia, 5 cases have been reported in Japan, and one case out of 5 cases were detected by CT scan. We thought that CT scans were useful procedures for early diagnosis of hepatic abscesses. Recently, the patient has continued complete remission hematologically.

  16. Automated volumetry of temporal horn of lateral ventricle for detection of Alzheimer's disease in CT scan

    Science.gov (United States)

    Takahashi, Noriyuki; Kinoshita, Toshibumi; Ohmura, Tomomi; Matsuyama, Eri; Toyoshima, Hideto

    2018-02-01

    The rapid increase in the incidence of Alzheimer's disease (AD) has become a critical issue in low and middle income countries. In general, MR imaging has become sufficiently suitable in clinical situations, while CT scan might be uncommonly used in the diagnosis of AD due to its low contrast between brain tissues. However, in those countries, CT scan, which is less costly and readily available, will be desired to become useful for the diagnosis of AD. For CT scan, the enlargement of the temporal horn of the lateral ventricle (THLV) is one of few findings for the diagnosis of AD. In this paper, we present an automated volumetry of THLV with segmentation based on Bayes' rule on CT images. In our method, first, all CT data sets are normalized into an atlas by using linear affine transformation and non-linear wrapping techniques. Next, a probability map of THLV is constructed in the normalized data. Then, THLV regions are extracted based on Bayes' rule. Finally, the volume of the THLV is evaluated. This scheme was applied to CT scans from 20 AD patients and 20 controls to evaluate the performance of the method for detecting AD. The estimated THLV volume was markedly increased in the AD group compared with the controls (P < .0001), and the area under the receiver operating characteristic curve (AUC) was 0.921. Therefore, this computerized method may have the potential to accurately detect AD on CT images.

  17. Research on defect detection from incomplete scanning of X-ray

    International Nuclear Information System (INIS)

    Zhang Shunli; Zhang Dinghua; Cheng Yunyong; Li Xiaolin

    2011-01-01

    Computed tomography (CT) is an advanced means of non-destructive testing, which has been widely used in medical and industrial fields. Aiming at the non-destructive testing problem of large industrial components, It presents a defect detection method from incomplete scanning of X-ray. Firstly, a set of incomplete scanning projection data before using the component has been obtained, then reconstruct them by algebraic re- construction technique (ART), and take the reconstructed images as the norm images. Then, the incomplete projection data of different times during the use of the component has been obtained, and reconstruct them by ART algorithm. Finally, It makes digital subtraction operation by the reconstructed images and the norm images, the defection can be detected clearly and intuitively from the subtraction image. Experimental result shows the proposed method is effective. (authors)

  18. KRAS and BRAF mutations in anal carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  19. Autoradiographical Detection of Tritium in Cu-Ni Alloy by Scanning Electron Microscopy

    OpenAIRE

    高安, 紀; 中野, 美樹; 竹内, 豊三郎

    1981-01-01

    The autoradiograph of tritium dispersed in Cu-Ni alloy sheet by 6Li(n,α)3H reaction was obtained by a scanning electron microscope. Prior to the irradiation of neutrons 6Li was deposited on the sheet by evaporation. The liquid emulsion, Fuji-ER, was used in this study. The distribution of tritium was detected by the dispersion of silver grains remaining in the emulsion after the development was carried out.

  20. 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.

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

    International Nuclear Information System (INIS)

    Lee, Jeong Ah; Lee, Seung Hun; Joo, Kyung Bin; Ryu, Jeong Ah; Kim, Tae Hwan

    2011-01-01

    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.

  2. Tc-99m sulfur colloid scanning in blunt trauma: detection of abdominal bleeding

    International Nuclear Information System (INIS)

    Bronfman, H.J.; Kunkel, B.K.; Rabin, H.S.

    1981-01-01

    Tc-99m sulfur colloid scintigraphy can detect and locate active lower gastrointestinal bleeding. The same principles apply to the detection and location of active intra-abdominal or pelvic hemorrhage following blunt abdominal trauma. We report two patients with abdominal bleeding who were correctly diagnosed by this method. As part of the routine examination of all patients having Tc-99m sulfur colloid liver-spleen scans for trauma, 500,000-count images should be made of the rest of the abdomen and pelvis

  3. Small nodule detectability evaluation using a generalized scan-statistic model

    International Nuclear Information System (INIS)

    Popescu, Lucretiu M; Lewitt, Robert M

    2006-01-01

    In this paper is investigated the use of the scan statistic for evaluating the detectability of small nodules in medical images. The scan-statistic method is often used in applications in which random fields must be searched for abnormal local features. Several results of the detection with localization theory are reviewed and a generalization is presented using the noise nodule distribution obtained by scanning arbitrary areas. One benefit of the noise nodule model is that it enables determination of the scan-statistic distribution by using only a few image samples in a way suitable both for simulation and experimental setups. Also, based on the noise nodule model, the case of multiple targets per image is addressed and an image abnormality test using the likelihood ratio and an alternative test using multiple decision thresholds are derived. The results obtained reveal that in the case of low contrast nodules or multiple nodules the usual test strategy based on a single decision threshold underperforms compared with the alternative tests. That is a consequence of the fact that not only the contrast or the size, but also the number of suspicious nodules is a clue indicating the image abnormality. In the case of the likelihood ratio test, the multiple clues are unified in a single decision variable. Other tests that process multiple clues differently do not necessarily produce a unique ROC curve, as shown in examples using a test involving two decision thresholds. We present examples with two-dimensional time-of-flight (TOF) and non-TOF PET image sets analysed using the scan statistic for different search areas, as well as the fixed position observer

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

    International Nuclear Information System (INIS)

    Hamar, G.; Varga, D.

    2012-01-01

    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. -- Highlights: ► First demonstration of Thick GEM surface scanning with single photo-electrons. ► Resolution of 0.1 mm is sufficient to identify structures connected to TGEM surface field structure. ► Gain and detection efficiency and separately measurable. ► Detection efficiency is high in a ring around the holes, and gain is constant in the hexagonal collection regions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hamar, G., E-mail: hamar.gergo@wigner.mta.hu [Wigner Research Centre for Physics, Budapest (Hungary); Varga, D., E-mail: vdezso@mail.cern.ch [Eoetvoes Lorand University, Budapest (Hungary)

    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. -- Highlights: Black-Right-Pointing-Pointer First demonstration of Thick GEM surface scanning with single photo-electrons. Black-Right-Pointing-Pointer Resolution of 0.1 mm is sufficient to identify structures connected to TGEM surface field structure. Black-Right-Pointing-Pointer Gain and detection efficiency and separately measurable. Black-Right-Pointing-Pointer Detection efficiency is high in a ring around the holes, and gain is constant in the hexagonal collection regions.

  6. Prospective evaluation of radionuclide scanning in detection of intestinal necrosis in neonatal necrotizing enterocolitis

    International Nuclear Information System (INIS)

    Haase, G.M.; Sfakianakis, G.N.; Lobe, T.E.; Boles, E.T.

    1981-01-01

    The ability of external imaging to demonstrate intestinal infarction in neonatal necrotizing enterocolitis (NEC) was prospectively evaluated. The radiopharmaceutical technetium--99m diphosphonate was injected intravenously and the patients subsequently underwent abdominal scanning. Clinical patient care and interpretation of the images were entirely independent throughout the study. Of 33 studies, 7 were positive, 4 were suspicious, and 22 were negative. One false positive study detected ischemia without transmural infarction. The second false positive scan occurred postoperatively and was due to misinterpretation of the hyperactivity along the surgical incision. None of the suspicious cases had damaged bowel. The two false negative studies clearly failed to demonstrate frank intestinal necrosis. The presence of very small areas of infarction, errors in technical settings, subjective interpretation of scans and delayed clearance of the radionuclide in a critically ill neonate may all limit the accuracy of external abdominal scanning. However, in spite of an error rate of 12%, it is likely that this technique will enhance the present clinical, laboratory, and radiologic parameters of patient management in NEC

  7. Detection of coronary artery disease - comparison of exercise stress radionuclide angiocardiography and thallium stress perfusion scanning

    International Nuclear Information System (INIS)

    Jengo, J.A.; Freeman, R.; Brizendine, M.; Mena, I.; St. Mary Medical Center, Long Beach, Calif.)

    1980-01-01

    Exercise thallium scanning and stress radionuclide angiography were compared in 16 normal subjects and 42 patients with more than 75% coronary arterial obstruction in studies using upright exercise on a bicycle ergometer. Studies at rest were subsequently obtained. Exercise thallium scans in the control group were normal in 15 and showed a defect in 1. Ejection fraction increased in all 16. During exercise, regional wall motion increased uniformly. In the group with coronary artery disease, thallium scanning revealed a new defect in the distribution of the involved arteries in 24 patients. In 15 who had a defect at rest, no new defect developed, but in 9 of the 15 new segmental wall motion defects were evident on radionuclide angiography. With exercise, ejection fraction decreased slightly. Regional wall motion abnormalities developed in the areas corresponding to thallium defects in all. Thallium scanning had a 93% and radionuclide angiography a 98% sensitivity value in detecting coronary artery disease. The respective specificity values were 94 and 100%. In patients with prior myocardial infarction who manifested new exercise abnormalities, 50% showed new thallium defects and 81% new wall motion defects

  8. Detecting Stems in Dense and Homogeneous Forest Using Single-Scan TLS

    Directory of Open Access Journals (Sweden)

    Shaobo Xia

    2015-10-01

    Full Text Available Stem characteristics of plants are of great importance to both ecology study and forest management. Terrestrial laser scanning (TLS may provide an effective way to characterize the fine-scale structures of vegetation. However, clumping plants, dense foliage and thin structure could intensify the shadowing effect and pose a series of problems in identifying stems, distinguishing neighboring stems, and merging disconnected stem parts in point clouds. This paper presents a new method to automatically detect stems in dense and homogeneous forest using single-scan TLS data. Stem points are first identified with a two-scale classification method. Then a clustering approach is used to group the candidate stem points. Finally, a direction-growing algorithm based on a simple stem curve model is applied to merge stem points. Field experiments were carried out in two different bamboo plots with a stem density of about 7500 stems/ha. Overall accuracy of the stem detection is 88% and the quality of detected stems is mainly affected by the shadowing effect. Results indicate that the proposed method is feasible and effective in detection of bamboo stems using TLS data, and can be applied to other species of single-stem plants in dense forests.

  9. KRAS mutation testing in colorectal cancer: comparison of the results obtained using 3 different methods for the analysis of codons G12 and G13.

    Science.gov (United States)

    Bihl, Michel P; Hoeller, Sylvia; Andreozzi, Maria Carla; Foerster, Anja; Rufle, Alexander; Tornillo, Luigi; Terracciano, Luigi

    2012-03-01

    Targeting the epidermal growth factor receptor (EGFR) is a new therapeutic option for patients with metastatic colorectal or lung carcinoma. However, the therapy efficiency highly depends on the KRAS mutation status in the given tumour. Therefore a reliable and secure KRAS mutation testing is crucial. Here we investigated 100 colorectal carcinoma samples with known KRAS mutation status (62 mutated cases and 38 wild type cases) in a comparative manner with three different KRAS mutation testing techniques (Pyrosequencing, Dideoxysequencing and INFINITI) in order to test their reliability and sensitivity. For the large majority of samples (96/100, 96%), the KRAS mutation status obtained by all three methods was the same. Only two cases with clear discrepancies were observed. One case was reported as wild type by the INFINITI method while the two other methods detected a G13C mutation. In the second case the mutation could be detected by the Pyrosequencing and INFINITI method (15% and 15%), while no signal for mutation could be observed with the Dideoxysequencing method. Additional two unclear results were due to a detection of a G12V with the INFINITI method, which was below cut-off when repeated and which was not detectable by the other two methods and very weak signals in a G12V mutated case with the Dideoxy- and Pyroseqencing method compared to the INFINITI method, respectively. In summary all three methods are reliable and robust methods in detecting KRAS mutations. INFINITI, however seems to be slightly more sensitive compared to Dideoxy- and Pyrosequencing.

  10. Ultrasound detection of pneumothorax compared with chest X-ray and computed tomography scan.

    Science.gov (United States)

    Nagarsheth, Khanjan; Kurek, Stanley

    2011-04-01

    Pneumothorax after trauma can be a life threatening injury and its care requires expeditious and accurate diagnosis and possible intervention. We performed a prospective, single blinded study with convenience sampling at a Level I trauma center comparing thoracic ultrasound with chest X-ray and CT scan in the detection of traumatic pneumothorax. Trauma patients that received a thoracic ultrasound, chest X-ray, and chest CT scan were included in the study. The chest X-rays were read by a radiologist who was blinded to the thoracic ultrasound results. Then both were compared with CT scan results. One hundred and twenty-five patients had a thoracic ultrasound performed in the 24-month period. Forty-six patients were excluded from the study due to lack of either a chest X-ray or chest CT scan. Of the remaining 79 patients there were 22 positive pneumothorax found by CT and of those 18 (82%) were found on ultrasound and 7 (32%) were found on chest X-ray. The sensitivity of thoracic ultrasound was found to be 81.8 per cent and the specificity was found to be 100 per cent. The sensitivity of chest X-ray was found to be 31.8 per cent and again the specificity was found to be 100 per cent. The negative predictive value of thoracic ultrasound for pneumothorax was 0.934 and the negative predictive value for chest X-ray for pneumothorax was found to be 0.792. We advocate the use of chest ultrasound for detection of pneumothorax in trauma patients.

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

    Science.gov (United States)

    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.

  12. The signature-based radiation-scanning approach to standoff detection of improvised explosive devices

    International Nuclear Information System (INIS)

    Brewer, R.L.; Dunn, W.L.; Heider, S.; Matthew, C.; Yang, X.

    2012-01-01

    The signature-based radiation-scanning technique for detection of improvised explosive devices is described. The technique seeks to detect nitrogen-rich chemical explosives present in a target. The technology compares a set of “signatures” obtained from a test target to a collection of “templates”, sets of signatures for a target that contain an explosive in a specific configuration. Interrogation of nitrogen-rich fertilizer samples, which serve as surrogates for explosives, is shown experimentally to be able to discriminate samples of 3.8 L and larger. - Highlights: ► Signature-based radiation-scanning techniques applied to detection of explosives. ► Nitrogen-rich fertilizer samples served as surrogate explosive samples. ► Signatures of a target compared to collections of templates of surrogate explosives. ► Figure-of-merit determined for neutron and neutron-induced gamma-ray signatures. ► Discrimination of surrogate explosive from inert samples of 3.8 L and larger.

  13. Motion Detection from Mobile Robots with Fuzzy Threshold Selection in Consecutive 2D Laser Scans

    Directory of Open Access Journals (Sweden)

    María A. Martínez

    2015-01-01

    Full Text Available Motion detection and tracking is a relevant problem for mobile robots during navigation to avoid collisions in dynamic environments or in applications where service robots interact with humans. This paper presents a simple method to distinguish mobile obstacles from the environment that is based on applying fuzzy threshold selection to consecutive two-dimensional (2D laser scans previously matched with robot odometry. The proposed method has been tested with the Auriga-α mobile robot in indoors to estimate the motion of nearby pedestrians.

  14. 111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

    International Nuclear Information System (INIS)

    Rubin, R.H.; Fischman, A.J.; Callahan, R.J.; Khaw, B.A.; Keech, F.; Ahmad, M.; Wilkinson, R.; Strauss, H.W.

    1989-01-01

    We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Morawski, Ireneusz [Peter Grünberg Institut (PGI-3) and JARA-Fundamentals of Future Information Technology, Forschungszentrum Jülich, 52425 Jülich (Germany); Institute of Experimental Physics, University of Wrocław, pl. M. Borna 9, 50-204 Wrocław (Poland); Spiegelberg, Richard; Korte, Stefan; Voigtländer, Bert [Peter Grünberg Institut (PGI-3) and JARA-Fundamentals of Future Information Technology, Forschungszentrum Jülich, 52425 Jülich (Germany)

    2015-12-15

    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.

  17. A FEASIBILITY STUDY ON USE OF GENERIC MOBILE LASER SCANNING SYSTEM FOR DETECTING ASPHALT PAVEMENT CRACKS

    Directory of Open Access Journals (Sweden)

    X. Chen

    2016-06-01

    Full Text Available This study aims to automatically detect pavement cracks on urban roads by employing the 3D point clouds acquired by a mobile laser scanning (MLS system. Our method consists of four steps: ground point filtering, high-pass convolution, matched filtering, and noise removal. First, a voxel-based upward growing method is applied to construct Digital Terrain Model (DTM of the road surface. Then, a high-pass filter convolutes the DTM to detect local elevation changes that may embed cracking information. Next, a two-step matched filter is applied to extract crack features. Lastly, a noise removal process is conducted to refine the results. Instead of using MLS intensity, this study takes advantages of the MLS elevation information to perform automated crack detection from large-volume, mixed-density, unstructured MLS point clouds. Four types of cracks including longitudinal, transvers, random, and alligator cracks are detected. Our results demonstrated that the proposed method works well with the RIEGL VMX-450 point clouds and can detect cracks in moderate-to-severe severity (13 - 25 mm within a 200 m by 30 m urban road segment located in Kingston, Ontario, at one time. Due to the resolution capability, small cracks with slight severity remain unclear in the MLS point cloud.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Confocal laser scanning microscopy detection of chlorophylls and carotenoids in chloroplasts and chromoplasts of tomato fruit.

    Science.gov (United States)

    D'Andrea, Lucio; Amenós, Montse; Rodríguez-Concepción, Manuel

    2014-01-01

    Plant cells are unique among eukaryotic cells because of the presence of plastids, including chloroplasts and chromoplasts. Chloroplasts are found in green tissues and harbor the photosynthetic machinery (including chlorophyll molecules), while chromoplasts are present in non-photosynthetic tissues and accumulate large amounts of carotenoids. During tomato fruit development, chloroplasts are converted into chromoplasts that accumulate high levels of lycopene, a linear carotenoid responsible for the characteristic red color of ripe fruit. Here, we describe a simple and fast method to detect both types of fully differentiated plastids (chloroplasts and chromoplasts), as well as intermediate stages, in fresh tomato fruits. The method is based on the differential autofluorescence of chlorophylls and carotenoids (lycopene) detected by Confocal Laser Scanning Microscopy.

  20. Design of the scanning mode coated glass color difference online detection system

    Science.gov (United States)

    Bi, Weihong; Zhang, Yu; Wang, Dajiang; Zhang, Baojun; Fu, Guangwei

    2008-03-01

    A design of scanning mode coated glass color difference online detection system was introduced. The system consisted of color difference data acquirement part and orbit control part. The function of the color difference data acquirement part was to acquire glass spectral reflectance and then processed them to get the color difference value. Using fiber for light guiding, the reflected light from surface of glass was transmitted into light division part, and the dispersive light was imaged on linear CCD, and then the output signals from the CCD was sampled pixel by pixel, and the spectral reflectance of coated glass was obtained finally. Then, the acquired spectral reflectance signals was sent to industrial personal computer through USB interface, using standard color space and color difference formula nominated by International Commission on Illumination (CIE) in 1976 to process these signals, and the reflected color parameter and color difference of coated glass was gained in the end. The function of the orbit control part was to move the detection probe by way of transverse scanning mode above the glass strip, and control the measuring start-stop time of the color difference data acquirement part at the same time. The color difference data acquirement part of the system was put on the orbit which is after annealing area in coated glass production line, and the protected fiber probe was placed on slide of the orbit. Using single chip microcomputer to control transmission mechanism of the slide, which made the slide move by way of transverse scanning mode on the glass strip, meanwhile, the color difference data acquirement part of the system was also controlled by the single chip microcomputer, and it made the acquirement part measure color difference data when the probe reached the needed working speed and required place on the glass strip. The scanning mode coated glass color difference online detection system can measure color parameter and color difference of

  1. Automated surface-scanning detection of pathogenic bacteria on fresh produce

    Science.gov (United States)

    Horikawa, Shin; Du, Songtao; Liu, Yuzhe; Chen, I.-Hsuan; Xi, Jianguo; Crumpler, Michael S.; Sirois, Donald L.; Best, Steve R.; Wikle, Howard C.; Chin, Bryan A.

    2017-05-01

    This paper investigates the effects of surface-scanning detector position on the resonant frequency and signal amplitude of a wireless magnetoelastic (ME) biosensor for direct pathogen detection on solid surfaces. The experiments were conducted on the surface of a flat polyethylene (PE) plate as a model study. An ME biosensor (1 mm × 0.2 mm × 30 μm) was placed on the PE surface, and a surface-scanning detector was brought close and aligned to the sensor for wireless resonant frequency measurement. The position of the detector was accurately controlled by using a motorized three-axis translation system (i.e., controlled X, Y, and Z positions). The results showed that the resonant frequency variations of the sensor were -125 to +150 Hz for X and Y detector displacements of +/-600 μm and Z displacements of +100 to +500 μm. These resonant frequency variations were small compared to the sensor's initial resonant frequency (< 0.007% of 2.2 MHz initial resonant frequency) measured at the detector home position, indicating high accuracy of the measurement. In addition, the signal amplitude was, as anticipated, found to decrease exponentially with increasing detection distance (i.e., Z distance). Finally, additional experiments were conducted on the surface of cucumbers. Similar results were obtained.

  2. Fast Edge Detection and Segmentation of Terrestrial Laser Scans Through Normal Variation Analysis

    Science.gov (United States)

    Che, E.; Olsen, M. J.

    2017-09-01

    Terrestrial Laser Scanning (TLS) utilizes light detection and ranging (lidar) to effectively and efficiently acquire point cloud data for a wide variety of applications. Segmentation is a common procedure of post-processing to group the point cloud into a number of clusters to simplify the data for the sequential modelling and analysis needed for most applications. This paper presents a novel method to rapidly segment TLS data based on edge detection and region growing. First, by computing the projected incidence angles and performing the normal variation analysis, the silhouette edges and intersection edges are separated from the smooth surfaces. Then a modified region growing algorithm groups the points lying on the same smooth surface. The proposed method efficiently exploits the gridded scan pattern utilized during acquisition of TLS data from most sensors and takes advantage of parallel programming to process approximately 1 million points per second. Moreover, the proposed segmentation does not require estimation of the normal at each point, which limits the errors in normal estimation propagating to segmentation. Both an indoor and outdoor scene are used for an experiment to demonstrate and discuss the effectiveness and robustness of the proposed segmentation method.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Van Damme, Nancy; Pauwels, Patrick; Peeters, Marc; Deron, Philippe; Van Roy, Nadine; Demetter, Pieter; Bols, Alain; Dorpe, Jo Van; Baert, Filip; Van Laethem, Jean-Luc; Speleman, Franki

    2010-01-01

    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. 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. 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. 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. This indicates that EGFR and K-RAS mutation analysis is not

  6. 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

  7. Alterations in the K-ras and p53 genes in rat lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Swafford, D.S.; Finch, G.L.; Mitchell, C.E. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)] [and others

    1997-06-01

    Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. The transition mutations formed could have been derived from deamination of cytosine. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 of 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors. 2 figs., 2 tabs., 48 refs.

  8. Analytical sensitivity of Tc99m radionuclide 'milk' scanning in the detection of gastro-oesophageal reflux

    Energy Technology Data Exchange (ETDEWEB)

    Paton, J.Y.; Nanayakkara, C.S.; Cosgriff, P.S.

    1985-09-01

    The analytical sensitivity of radionuclide ''milk'' scans for detecting gastro-oesophageal reflux (GOR) has been assessed using an in vitro simulation test. Five factors were found to affect the ability to detect simulated reflux: isotope concentration, absolute gamma camera sensitivity, absorber thickness overlying the ''oesophagus'' and volume and duration of reflux. We found that a critical volume-duration product must be exceeded for reflux to be detected. Radionuclide milk scanning appears to be much less sensitive in detecting transient events like GOR than might be expected from previously reported static simulation studies.

  9. Automatic Feature Detection, Description and Matching from Mobile Laser Scanning Data and Aerial Imagery

    Science.gov (United States)

    Hussnain, Zille; Oude Elberink, Sander; Vosselman, George

    2016-06-01

    In mobile laser scanning systems, the platform's position is measured by GNSS and IMU, which is often not reliable in urban areas. Consequently, derived Mobile Laser Scanning Point Cloud (MLSPC) lacks expected positioning reliability and accuracy. Many of the current solutions are either semi-automatic or unable to achieve pixel level accuracy. We propose an automatic feature extraction method which involves utilizing corresponding aerial images as a reference data set. The proposed method comprise three steps; image feature detection, description and matching between corresponding patches of nadir aerial and MLSPC ortho images. In the data pre-processing step the MLSPC is patch-wise cropped and converted to ortho images. Furthermore, each aerial image patch covering the area of the corresponding MLSPC patch is also cropped from the aerial image. For feature detection, we implemented an adaptive variant of Harris-operator to automatically detect corner feature points on the vertices of road markings. In feature description phase, we used the LATCH binary descriptor, which is robust to data from different sensors. For descriptor matching, we developed an outlier filtering technique, which exploits the arrangements of relative Euclidean-distances and angles between corresponding sets of feature points. We found that the positioning accuracy of the computed correspondence has achieved the pixel level accuracy, where the image resolution is 12cm. Furthermore, the developed approach is reliable when enough road markings are available in the data sets. We conclude that, in urban areas, the developed approach can reliably extract features necessary to improve the MLSPC accuracy to pixel level.

  10. [Automated detection and volumetric segmentation of the spleen in CT scans].

    Science.gov (United States)

    Hammon, M; Dankerl, P; Kramer, M; Seifert, S; Tsymbal, A; Costa, M J; Janka, R; Uder, M; Cavallaro, A

    2012-08-01

    To introduce automated detection and volumetric segmentation of the spleen in spiral CT scans with the THESEUS-MEDICO software. The consistency between automated volumetry (aV), estimated volume determination (eV) and manual volume segmentation (mV) was evaluated. Retrospective evaluation of the CAD system based on methods like "marginal space learning" and "boosting algorithms". 3 consecutive spiral CT scans (thoraco-abdominal; portal-venous contrast agent phase; 1 or 5 mm slice thickness) of 15 consecutive lymphoma patients were included. The eV: 30 cm³ + 0.58 (width × length × thickness of the spleen) and the mV as the reference standard were determined by an experienced radiologist. The aV could be performed in all CT scans within 15.2 (± 2.4) seconds. The average splenic volume measured by aV was 268.21 ± 114.67 cm³ compared to 281.58 ± 130.21 cm³ in mV and 268.93 ± 104.60 cm³ in eV. The correlation coefficient was 0.99 (coefficient of determination (R²) = 0.98) for aV and mV, 0.91 (R² = 0.83) for mV and eV and 0.91 (R² = 0.82) for aV and eV. There was an almost perfect correlation of the changes in splenic volume measured with the new aV and mV (0.92; R² = 0.84), mV and eV (0.95; R² = 0.91) and aV and eV (0.83; R² = 0.69) between two time points. The automated detection and volumetric segmentation software rapidly provides an accurate measurement of the splenic volume in CT scans. Knowledge about splenic volume and its change between two examinations provides valuable clinical information without effort for the radiologist. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Automated detection and volumetric segmentation of the spleen in CT scans

    International Nuclear Information System (INIS)

    Hammon, M.; Dankerl, P.; Janka, R.; Uder, M.; Cavallaro, A.; Kramer, M.; Seifert, S.; Tsymbal, A.; Costa, M.J.

    2012-01-01

    To introduce automated detection and volumetric segmentation of the spleen in spiral CT scans with the THESEUS-MEDICO software. The consistency between automated volumetry (aV), estimated volume determination (eV) and manual volume segmentation (mV) was evaluated. Retrospective evaluation of the CAD system based on methods like ''marginal space learning'' and ''boosting algorithms''. 3 consecutive spiral CT scans (thoraco-abdominal; portal-venous contrast agent phase; 1 or 5 mm slice thickness) of 15 consecutive lymphoma patients were included. The eV: 30 cm 3 + 0.58 (width x length x thickness of the spleen) and the mV as the reference standard were determined by an experienced radiologist. The aV could be performed in all CT scans within 15.2 (± 2.4) seconds. The average splenic volume measured by aV was 268.21 ± 114.67 cm 3 compared to 281.58 ± 130.21 cm 3 in mV and 268.93 ± 104.60 cm 3 in eV. The correlation coefficient was 0.99 (coefficient of determination (R 2 ) = 0.98) for aV and mV, 0.91 (R 2 = 0.83) for mV and eV and 0.91 (R 2 = 0.82) for aV and eV. There was an almost perfect correlation of the changes in splenic volume measured with the new aV and mV (0.92; R 2 = 0.84), mV and eV (0.95; R 2 = 0.91) and aV and eV (0.83; R 2 = 0.69) between two time points. The automated detection and volumetric segmentation software rapidly provides an accurate measurement of the splenic volume in CT scans. Knowledge about splenic volume and its change between two examinations provides valuable clinical information without effort for the radiologist. (orig.)

  12. Digitally generated excitation and near-baseband quadrature detection of rapid scan EPR signals.

    Science.gov (United States)

    Tseitlin, Mark; Yu, Zhelin; Quine, Richard W; Rinard, George A; Eaton, Sandra S; Eaton, Gareth R

    2014-12-01

    The use of multiple synchronized outputs from an arbitrary waveform generator (AWG) provides the opportunity to perform EPR experiments differently than by conventional EPR. We report a method for reconstructing the quadrature EPR spectrum from periodic signals that are generated with sinusoidal magnetic field modulation such as continuous wave (CW), multiharmonic, or rapid scan experiments. The signal is down-converted to an intermediate frequency (IF) that is less than the field scan or field modulation frequency and then digitized in a single channel. This method permits use of a high-pass analog filter before digitization to remove the strong non-EPR signal at the IF, that might otherwise overwhelm the digitizer. The IF is the difference between two synchronized X-band outputs from a Tektronix AWG 70002A, one of which is for excitation and the other is the reference for down-conversion. To permit signal averaging, timing was selected to give an exact integer number of full cycles for each frequency. In the experiments reported here the IF was 5kHz and the scan frequency was 40kHz. To produce sinusoidal rapid scans with a scan frequency eight times IF, a third synchronized output generated a square wave that was converted to a sine wave. The timing of the data acquisition with a Bruker SpecJet II was synchronized by an external clock signal from the AWG. The baseband quadrature signal in the frequency domain was reconstructed. This approach has the advantages that (i) the non-EPR response at the carrier frequency is eliminated, (ii) both real and imaginary EPR signals are reconstructed from a single physical channel to produce an ideal quadrature signal, and (iii) signal bandwidth does not increase relative to baseband detection. Spectra were obtained by deconvolution of the reconstructed signals for solid BDPA (1,3-bisdiphenylene-2-phenylallyl) in air, 0.2mM trityl OX63 in water, 15 N perdeuterated tempone, and a nitroxide with a 0.5G partially-resolved proton

  13. 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.

  14. CT Scan

    Science.gov (United States)

    ... disease, lung nodules and liver masses Monitor the effectiveness of certain treatments, such as cancer treatment Detect ... scan done in a hospital or an outpatient facility. CT scans are painless and, with newer machines, ...

  15. 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.)

  16. Detection of treatment setup errors between two CT scans for patients with head and neck cancer

    International Nuclear Information System (INIS)

    Ezzell, Leah C.; Hansen, Eric K.; Quivey, Jeanne M.; Xia Ping

    2007-01-01

    Accuracy of treatment setup for head and neck patients undergoing intensity-modulated radiation therapy is of paramount importance. The conventional method using orthogonal portal images can only detect translational setup errors while the most frequent setup errors for head and neck patients could be rotational errors. With the rapid development of image-guided radiotherapy, three-dimensional images are readily acquired and can be used to detect both translational and rotational setup errors. The purpose of this study is to determine the significance of rotational variations between two planning CT scans acquired for each of eight head and neck patients, who experienced substantial weight loss or tumor shrinkage. To this end, using a rigid body assumption, we developed an in-house computer program that utilizes matrix transformations to align point bony landmarks with an incremental best-fit routine. The program returns the quantified translational and rotational shifts needed to align the scans of each patient. The program was tested using a phantom for a set of known translational and rotational shifts. For comparison, a commercial treatment planning system was used to register the two CT scans and estimate the translational errors for these patients. For the eight patients, we found that the average magnitudes and standard deviations of the rotational shifts about the transverse, anterior-posterior, and longitudinal axes were 1.7±2.3 deg., 0.8±0.7 deg., and 1.8±1.1 deg., respectively. The average magnitudes and standard deviations of the translational shifts were 2.5±2.6 mm, 2.9±2.8 mm, 2.7±1.7 mm while the differences detected between our program and the CT-CT fusion method were 1.8±1.3 mm, 3.3±5.4 mm, and 3.0±3.4 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. A trend of larger rotational errors resulting in larger translational differences between the two methods was observed. In conclusion, conventional

  17. Using rapid-scan EPR to improve the detection limit of quantitative EPR by more than one order of magnitude.

    Science.gov (United States)

    Möser, J; Lips, K; Tseytlin, M; Eaton, G R; Eaton, S S; Schnegg, A

    2017-08-01

    X-band rapid-scan EPR was implemented on a commercially available Bruker ELEXSYS E580 spectrometer. Room temperature rapid-scan and continuous-wave EPR spectra were recorded for amorphous silicon powder samples. By comparing the resulting signal intensities the feasibility of performing quantitative rapid-scan EPR is demonstrated. For different hydrogenated amorphous silicon samples, rapid-scan EPR results in signal-to-noise improvements by factors between 10 and 50. Rapid-scan EPR is thus capable of improving the detection limit of quantitative EPR by at least one order of magnitude. In addition, we provide a recipe for setting up and calibrating a conventional pulsed and continuous-wave EPR spectrometer for rapid-scan EPR. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. 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.

  1. ac driving amplitude dependent systematic error in scanning Kelvin probe microscope measurements: Detection and correction

    International Nuclear Information System (INIS)

    Wu Yan; Shannon, Mark A.

    2006-01-01

    The dependence of the contact potential difference (CPD) reading on the ac driving amplitude in scanning Kelvin probe microscope (SKPM) hinders researchers from quantifying true material properties. We show theoretically and demonstrate experimentally that an ac driving amplitude dependence in the SKPM measurement can come from a systematic error, and it is common for all tip sample systems as long as there is a nonzero tracking error in the feedback control loop of the instrument. We further propose a methodology to detect and to correct the ac driving amplitude dependent systematic error in SKPM measurements. The true contact potential difference can be found by applying a linear regression to the measured CPD versus one over ac driving amplitude data. Two scenarios are studied: (a) when the surface being scanned by SKPM is not semiconducting and there is an ac driving amplitude dependent systematic error; (b) when a semiconductor surface is probed and asymmetric band bending occurs when the systematic error is present. Experiments are conducted using a commercial SKPM and CPD measurement results of two systems: platinum-iridium/gap/gold and platinum-iridium/gap/thermal oxide/silicon are discussed

  2. 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.

  3. Detection of a magnetic bead by hybrid nanodevices using scanning gate microscopy

    Science.gov (United States)

    Corte-León, H.; Krzysteczko, P.; Marchi, F.; Motte, J.-F.; Manzin, A.; Schumacher, H. W.; Antonov, V.; Kazakova, O.

    2016-05-01

    Hybrid ferromagnetic(Py)/non-magnetic metal(Au) junctions with a width of 400 nm are studied by magnetotransport measurements, magnetic scanning gate microscopy (SGM) with a magnetic bead (MB) attached to the probe, and micromagnetic simulations. In the transverse geometry, the devices demonstrate a characteristic magnetoresistive behavior that depends on the direction of the in plane magnetic field, with minimum/maximum variation when the field is applied parallel/perpendicular to the Py wire. The SGM is performed with a NdFeB bead of 1.6 μm diameter attached to the scanning probe. Our results demonstrate that the hybrid junction can be used to detect this type of MB. A rough approximation of the sensing volume of the junction has the shape of elliptical cylinder with the volume of ˜1.51 μm3. Micromagnetic simulations coupled to a magnetotransport model including anisotropic magnetoresistance and planar Hall effects are in good agreement with the experimental findings, enabling the interpretation of the SGM images.

  4. Detection of a magnetic bead by hybrid nanodevices using scanning gate microscopy

    Directory of Open Access Journals (Sweden)

    H. Corte-León

    2016-05-01

    Full Text Available Hybrid ferromagnetic(Py/non-magnetic metal(Au junctions with a width of 400 nm are studied by magnetotransport measurements, magnetic scanning gate microscopy (SGM with a magnetic bead (MB attached to the probe, and micromagnetic simulations. In the transverse geometry, the devices demonstrate a characteristic magnetoresistive behavior that depends on the direction of the in plane magnetic field, with minimum/maximum variation when the field is applied parallel/perpendicular to the Py wire. The SGM is performed with a NdFeB bead of 1.6 μm diameter attached to the scanning probe. Our results demonstrate that the hybrid junction can be used to detect this type of MB. A rough approximation of the sensing volume of the junction has the shape of elliptical cylinder with the volume of ∼1.51 μm3. Micromagnetic simulations coupled to a magnetotransport model including anisotropic magnetoresistance and planar Hall effects are in good agreement with the experimental findings, enabling the interpretation of the SGM images.

  5. 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.

  6. Detection of soft tissue pathology on the blood pool phase of bone scans

    International Nuclear Information System (INIS)

    Raimondo, A.J.; Turner, H.A.; Kitchener, M.I.

    1999-01-01

    Full text: It is important to optimize information obtained from isotope bone scanning in musculoskeletal imaging. Although important at all times, it is especially imperative in the current climate of health services rationalization, capping of imaging expenditure and the promotion of newer modalities that are increasingly versatile and sensitive for imaging the musculoskeletal system. Careful attention must be paid to the blood flow and blood pool images, to visualize soft tissue as well as bony pathology. A series of cases and images will be presented that demonstrated blood pool pathology that was not appreciated on delayed imaging, or where reliance only on the delayed images would have led to an incorrect diagnosis. These include the detection of tendonitis, tenosynovitis, bursitis, muscle tears and soft tissue neoplasms, including neuromas. In cases where the bone scan cannot provide a definitive diagnosis, it will at least direct the referring clinician to the most appropriate confirmatory diagnostic imaging modality, thus reinforcing the value that isotope imaging provides in musculoskeletal medicine

  7. 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.

  8. 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....

  9. 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.

  10. 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

  11. 3D change detection at street level using mobile laser scanning point clouds and terrestrial images

    Science.gov (United States)

    Qin, Rongjun; Gruen, Armin

    2014-04-01

    Automatic change detection and geo-database updating in the urban environment are difficult tasks. There has been much research on detecting changes with satellite and aerial images, but studies have rarely been performed at the street level, which is complex in its 3D geometry. Contemporary geo-databases include 3D street-level objects, which demand frequent data updating. Terrestrial images provides rich texture information for change detection, but the change detection with terrestrial images from different epochs sometimes faces problems with illumination changes, perspective distortions and unreliable 3D geometry caused by the lack of performance of automatic image matchers, while mobile laser scanning (MLS) data acquired from different epochs provides accurate 3D geometry for change detection, but is very expensive for periodical acquisition. This paper proposes a new method for change detection at street level by using combination of MLS point clouds and terrestrial images: the accurate but expensive MLS data acquired from an early epoch serves as the reference, and terrestrial images or photogrammetric images captured from an image-based mobile mapping system (MMS) at a later epoch are used to detect the geometrical changes between different epochs. The method will automatically mark the possible changes in each view, which provides a cost-efficient method for frequent data updating. The methodology is divided into several steps. In the first step, the point clouds are recorded by the MLS system and processed, with data cleaned and classified by semi-automatic means. In the second step, terrestrial images or mobile mapping images at a later epoch are taken and registered to the point cloud, and then point clouds are projected on each image by a weighted window based z-buffering method for view dependent 2D triangulation. In the next step, stereo pairs of the terrestrial images are rectified and re-projected between each other to check the geometrical

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

    International Nuclear Information System (INIS)

    Bornholdt, Jette; Vogel, Ulla; Husgafvel-Pursiainen, Kirsti; Wallin, Håkan; Hansen, Johnni; Steiniche, Torben; Dictor, Michael; Antonsen, Annemarie; Wolff, Henrik; Schlünssen, Vivi; Holmila, Reetta; Luce, Danièle

    2008-01-01

    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 mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations. We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-ras codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data. Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-ras was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure. Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected

  13. 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.

  14. 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

  15. Optical detection of ultrasound using an apertureless near-field scanning optical microscopy system

    Science.gov (United States)

    Ahn, Phillip; Zhang, Zhen; Sun, Cheng; Balogun, Oluwaseyi

    2013-01-01

    Laser ultrasonics techniques are power approaches for non-contact generation and detection of high frequency ultrasound on a local scale. In these techniques, optical diffraction limits the spatial information that can be accessed from a measurement. In order to improve the lateral spatial resolution, we incorporate an apertureless near-field scanning optical microscope (aNSOM) into laser ultrasonics setup for local detection of laser generated ultrasound. The aNSOM technique relies on the measurement of a weak backscattered near-field light intensity resulting from the oblique illumination of a nanoscale probe-tip positioned close to a sample surface. We enhance the optical near-field intensity by coupling light to surface plasmon polaritons (SPPs) on the shaft of an atomic force microscopy (AFM) cantilever. The SPPs propagate down the AFM shaft, localize at the tip apex, and are backscattered to the far-field when the separation distance between the probe tip and the sample surface is comparable to the probe-tip radius. The backscattered near-field intensity is dynamically modulated when an ultrasonic wave arrives at the sample surface leading to a transient change in the tip-sample separation distance. We present experimental results detailing measurement of broadband and narrowband laser generated ultrasound in solids with frequencies reaching up to 180 MHz range.

  16. Fluorescent nanoscale detection of biotin-streptavidin interaction using near-field scanning optical microscopy

    International Nuclear Information System (INIS)

    Park, Hyun Kyu; Chung, Bong Hyun; Gokarna, Anisha; Hulme, John P; Park, Hyun Gyu

    2008-01-01

    We describe a nanoscale strategy for detecting biotin-streptavidin binding using near-field scanning optical microscopy (NSOM) that exploits the fluorescence properties of single polydiacetylene (PDA) liposomes. NSOM is more useful to observe nanomaterials having optical properties with the help of topological information. We synthesized amine-terminated 10,12-pentacosadiynoic acid (PCDA) monomer (PCDA-NH 2 ) and used this derivatized monomer to prepare PCDA liposomes. PCDA-NH 2 liposomes were immobilized on an aldehyde-functionalized glass surface followed by photopolymerization by using a 254 nm light source. To measure the biotin-streptavidin binding, we conjugated photoactivatable biotin to immobilized PCDA-NH 2 liposomes by UV irradiation (365 nm) and subsequently allowed them to interact with streptavidin. We analyzed the fluorescence using a fluorescence scanner and observed single liposomes using NSOM. The average height and NSOM signal observed in a single liposome after binding were ∼31.3 to 8.5 ± 0.5 nm and 0.37 to 0.16 ± 0.6 kHz, respectively. This approach, which has the advantage of not requiring a fluorescent label, could prove highly beneficial for single molecule detection technology

  17. 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.

  18. Anteroposterior chest radiograph vs. chest CT scan in early detection of pneumothorax in trauma patients

    Directory of Open Access Journals (Sweden)

    Omar Hesham R

    2011-09-01

    Full Text Available Abstract Pneumothorax is a common complication following blunt chest wall trauma. In these patients, because of the restrictions regarding immobilization of the cervical spine, Anteroposterior (AP chest radiograph is usually the most feasible initial study which is not as sensitive as the erect chest X-ray or CT chest for detection of a pneumothorax. We will present 3 case reports which serve for better understanding of the entity of occult pneumothorax. The first case is an example of a true occult pneumothorax where an initial AP chest X-ray revealed no evidence of pneumothorax and a CT chest immediately performed revealed evidence of pneumothorax. The second case represents an example of a missed rather than a truly occult pneumothorax where the initial chest radiograph revealed clues suggesting the presence of pneumothorax which were missed by the reading radiologist. The third case emphasizes the fact that "occult pneumothorax is predictable". The presence of subcutaneous emphesema and pulmonary contusion should call for further imaging with CT chest to rule out pneumothorax. Thoracic CT scan is therefore the "gold standard" for early detection of a pneumothorax in trauma patients. This report aims to sensitize readers to the entity of occult pneumothorax and create awareness among intensivists and ER physicians regarding the proper diagnosis and management.

  19. Anteroposterior chest radiograph vs. chest CT scan in early detection of pneumothorax in trauma patients.

    Science.gov (United States)

    Omar, Hesham R; Mangar, Devanand; Khetarpal, Suneel; Shapiro, David H; Kolla, Jaya; Rashad, Rania; Helal, Engy; Camporesi, Enrico M

    2011-09-27

    Pneumothorax is a common complication following blunt chest wall trauma. In these patients, because of the restrictions regarding immobilization of the cervical spine, Anteroposterior (AP) chest radiograph is usually the most feasible initial study which is not as sensitive as the erect chest X-ray or CT chest for detection of a pneumothorax. We will present 3 case reports which serve for better understanding of the entity of occult pneumothorax. The first case is an example of a true occult pneumothorax where an initial AP chest X-ray revealed no evidence of pneumothorax and a CT chest immediately performed revealed evidence of pneumothorax. The second case represents an example of a missed rather than a truly occult pneumothorax where the initial chest radiograph revealed clues suggesting the presence of pneumothorax which were missed by the reading radiologist. The third case emphasizes the fact that "occult pneumothorax is predictable". The presence of subcutaneous emphesema and pulmonary contusion should call for further imaging with CT chest to rule out pneumothorax. Thoracic CT scan is therefore the "gold standard" for early detection of a pneumothorax in trauma patients. This report aims to sensitize readers to the entity of occult pneumothorax and create awareness among intensivists and ER physicians regarding the proper diagnosis and management.

  20. 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.

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

    International Nuclear Information System (INIS)

    Cerne, Jasmina-Ziva; Stegel, Vida; Gersak, Ksenija; Novakovic, Srdjan

    2012-01-01

    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. 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. 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. 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

  2. Non-invasive and high-sensitivity scanning detection of magnetic nanoparticles in animals using high-Tc scanning superconducting-quantum-interference-device biosusceptometry.

    Science.gov (United States)

    Chieh, J J; Hong, C Y

    2011-08-01

    Although magnetic nanoparticles (MNPs) have been widely applied to animals in biomedicine, MNPs within animals should be examined in real time, in vivo, and without bio-damaged possibility to evaluate whether the bio-function of MNPs is valid or to further controls the biomedicinal process because of accompanying complex problems such as MNPs distribution and MNPs biodegradation. The non-invasive and high-sensitivity scanning detection of MNPs in animals using ac susceptometry based on a high-T(c) superconducting quantum interference device (SQUID) is presented. The non-invasive results and biopsy results show good agreement, and two gold-standard biomedicine methods, Prussian blue stain and inductively coupled plasma, prove the magnetic results. This confirms that the future clinical diagnosis of bio-functional MNPs could be operated by using scanning SQUID biosusceptometry as conveniently as an ultrasonic probe.

  3. 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

  4. EGFR and KRAS mutation coexistence in lung adenocarcinomas

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    Vitor Manuel Leitão de Sousa

    2015-04-01

    Full Text Available Lung cancer is one of the most common causes of cancer deaths. The development of EGFR targeted therapies, including monoclonal antibodies and tyrosine kinase inhibitors have generated an interest in the molecular characterization of these tumours. KRAS mutations are associated with resistance to EGFR TKIs. EGFR and KRAS mutations have been considered as mutually exclusive. This paper presents three bronchial-pulmonary carcinomas, two adenocarcinomas and one pleomorphic sarcomatoid carcinoma, harboring EGFR and KRAS mutations. Case 1 corresponded to an adenocarcinoma with EGFR exon 21 mutation (L858R and KRAS codon 12 point mutation (G12V; case 2, a  mucinous adenocarcinoma expressed coexistence of EGFR exon 21 mutation (L858R and KRAS codon 12 point mutation (G12V; and case 3 a sarcomatoid carcinoma with EGFR exon 19 deletion – del 9bp and KRAS codon 12 point mutation (G12C - cysteine. Based on our experience and on the literature, we conclude that EGFR and KRAS mutations can indeed coexist in the same bronchial-pulmonary carcinoma, either in the same histological type or in different patterns. The biological implications of this coexistence are still poorly understood mainly because these cases are not frequent or currently searched. It is therefore necessary to study larger series of cases with the two mutations to better understand the biological, clinical and therapeutic implications.

  5. Comparison of CT scan and colour flow doppler ultrasound in detecting venous tumour thrombous in renal cell carcinoma

    International Nuclear Information System (INIS)

    Khan, A.R.; Anwar, K.

    2008-01-01

    Renal cell carcinoma has marked tendency to spread into renal vein, inferior vena cava and right side of heart. Extension of tumour thrombus into these veins will alter the surgical approach. We have compared the CT scan with Colour flow Doppler ultrasound in detecting venous tumour thrombus in renal vein and inferior vena cava. This cross-sectional study included 30 adult patients presenting with renal tumour. Patients of either gender were included in the study. Non probability convenience sampling was used. All patients underwent colour flow Doppler ultrasound and CT scan with contrast to asses the renal vein and inferior vena cava. The results were confirmed by intra operative findings and histopathology. The data was analyzed using SPSS version 12. Out of 30 patients, 20 (66%) were males and 10 (34%) female. The tumour was predominantly on the right side (60%), as was renal venous tumour thrombus (44%). Inferior vena cava was involved in 4 cases predominantly due to right sided tumours. The sensitivity of Doppler ultrasound in detecting renal venous tumour thrombus (88% on right and 100% on left side) was higher than CT scan (63% on right and 60% on left side). Doppler ultrasound was also superior to CT scan in detecting vena caval thrombus. The overall sensitivity of Doppler sonography was higher than CT scan in detecting tumour extension into renal veins and inferior vena cava. Therefore, it can be used as a complementary tool in equivocal cases. (author)

  6. Application of 3D Laser Scanning Technology in Inspection and Dynamic Reserves Detection of Open-Pit Mine

    Science.gov (United States)

    Hu, Zhumin; Wei, Shiyu; Jiang, Jun

    2017-10-01

    The traditional open-pit mine mining rights verification and dynamic reserve detection means rely on the total station and RTK to collect the results of the turning point coordinates of mining surface contours. It resulted in obtaining the results of low precision and large error in the means that is limited by the traditional measurement equipment accuracy and measurement methods. The three-dimensional scanning technology can obtain the three-dimensional coordinate data of the surface of the measured object in a large area at high resolution. This paper expounds the commonly used application of 3D scanning technology in the inspection and dynamic reserve detection of open mine mining rights.

  7. Fast-scan cyclic voltammetry (FSCV) detection of endogenous octopamine in Drosophila melanogaster ventral nerve cord

    Science.gov (United States)

    Pyakurel, Poojan; Privman, Eve; Venton, B. Jill

    2016-01-01

    Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. An FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval VNC. Repeated stimulations were stable with 2 or 5 minutes interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain. PMID:27326831

  8. Development of a computer-aided diagnostic scheme for detection of interval changes in successive whole-body bone scans

    International Nuclear Information System (INIS)

    Shiraishi, Junji; Li Qiang; Appelbaum, Daniel; Pu Yonglin; Doi, Kunio

    2007-01-01

    Bone scintigraphy is the most frequent examination among various diagnostic nuclear medicine procedures. It is a well-established imaging modality for the diagnosis of osseous metastasis and for monitoring osseous tumor response to chemotherapy and radiation therapy. Although the sensitivity of bone scan examinations for detection of bone abnormalities has been considered to be relatively high, it is time consuming to identify multiple lesions such as bone metastases of prostate and breast cancers. In addition, it is very difficult to detect subtle interval changes between two successive abnormal bone scans, because of variations in patient conditions, the accumulation of radioisotopes during each examination, and the image quality of gamma cameras. Therefore, we developed a new computer-aided diagnostic (CAD) scheme for the detection of interval changes in successive whole-body bone scans by use of a temporal subtraction image which was obtained with a nonlinear image-warping technique. We carried out 58 pairs of successive bone scans in which each scan included both posterior and anterior views. We determined 107 'gold-standard' interval changes among the 58 pairs based on the consensus of three radiologists. Our computerized scheme consisted of seven steps, i.e., initial image density normalization on each image, image matching for the paired images, temporal subtraction by use of the nonlinear image-warping technique, initial detection of interval changes by use of temporal-subtraction images, image feature extraction of candidates of interval changes, rule-based tests by use of 16 image features for removing some false positives, and display of the computer output for identified interval changes. One hundred seven gold standard interval changes included 71 hot lesions (uptake was increased compared with the previous scan, or there was new uptake in the current scan) and 36 cold lesions (uptake was decreased or disappeared) for anterior and posterior views. The

  9. 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%.

  10. Temporal interpolation alters motion in fMRI scans: Magnitudes and consequences for artifact detection.

    Directory of Open Access Journals (Sweden)

    Jonathan D Power

    Full Text Available Head motion can be estimated at any point of fMRI image processing. Processing steps involving temporal interpolation (e.g., slice time correction or outlier replacement often precede motion estimation in the literature. From first principles it can be anticipated that temporal interpolation will alter head motion in a scan. Here we demonstrate this effect and its consequences in five large fMRI datasets. Estimated head motion was reduced by 10-50% or more following temporal interpolation, and reductions were often visible to the naked eye. Such reductions make the data seem to be of improved quality. Such reductions also degrade the sensitivity of analyses aimed at detecting motion-related artifact and can cause a dataset with artifact to falsely appear artifact-free. These reduced motion estimates will be particularly problematic for studies needing estimates of motion in time, such as studies of dynamics. Based on these findings, it is sensible to obtain motion estimates prior to any image processing (regardless of subsequent processing steps and the actual timing of motion correction procedures, which need not be changed. We also find that outlier replacement procedures change signals almost entirely during times of motion and therefore have notable similarities to motion-targeting censoring strategies (which withhold or replace signals entirely during times of motion.

  11. 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.

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

    Science.gov (United States)

    Lopes, Gil; Ribeiro, A Fernando; Sillero, Neftalí; Gonçalves-Seco, Luís; Silva, Cristiano; Franch, Marc; Trigueiros, Paulo

    2016-04-19

    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.

  13. A Control and Detecting System of Micro-Near-Infrared Spectrometer Based on a MOEMS Scanning Grating Mirror

    Directory of Open Access Journals (Sweden)

    Haitao Liu

    2018-03-01

    Full Text Available Based on the scanning grating mirror we developed, this paper presents a method of the precise control of a scanning grating mirror and of high-speed spectrum data detection. In addition, the system circuit of the scanning grating mirror control and spectrum signal detecting is designed and manufactured in this paper. The mirror control system includes a drive generator module, an amplitude detection module, a feedback control module, and a variable gain amplification (VGA module; the detecting system includes a field programmable gate array (FPGA main control module, a synchronous trigger module, an analog-digital conversion (ADC module, and a universal serial bus (USB interface module. The final results of the experiment show that the control system has successfully realized the precision control of the swing of the scanning grating mirror and that the detecting system has successfully realized the high-speed acquisition and transmission of the spectral signal and the angle signals. The spectrum has been reconstructed according to the mathematical relationship between the wavelength λ and the angle β of the mirror. The resolution of the spectrometer reaches 10 nm in the wavelength range of 800–1800 nm, the signal-to-noise ratio (SNR of the spectrometer is 4562 at full scale, the spectrum data drift is 0.9% in 24 h, and the precision of the closed loop control is 0.06%.

  14. [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, P cell proliferative activity of the miR-143 mimic group was significantly lower than that of the negative control group ( P cell proliferative activity of the miR-143 mimic+ K-ras group was also significantly lower than the control group ( P HeLa cells through targeted regulating the expression of K-ras gene. In human cervical cancer tissues of a small sample set, the expression of miR-143 is downregulated, and the expression of K-ras is upregulated.

  15. 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.

  16. Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective.

    Science.gov (United States)

    Ross, Jeffrey S

    2012-10-01

    Mutation status of the KRAS gene identifies a distinct disease subtype of metastatic colorectal carcinoma that does not respond to antibody therapeutics targeting the epidermal growth factor receptor. This is currently the only validated marker in metastatic colorectal carcinoma with a clear implication in treatment selection. KRAS testing is widely accepted in clinical practice to guide metastatic colorectal carcinoma therapeutic decisions, and there are many commercially available platforms to perform the test. To evaluate the critical role of pathologists in the full implementation of KRAS testing by optimizing tumor tissue collection and fixation procedures and by choosing testing technologies and reliable Clinical Laboratory Improvement Amendments of 1988-certified laboratories to perform the tests. Prospective clinical trials, retrospective studies, and quality assessment and survey reports were identified in the following databases: PubMed, American Society of Clinical Oncology Proceedings (American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancer Symposium) and European Society for Medical Oncology Proceedings (Annals of Oncology European Society for Medical Oncology Congress and Annals of Oncology World Congress on Gastrointestinal Cancers). More bona fide standards are needed to address the variety of available test methods, which have different performance characteristics including speed, sensitivity to detect rare mutations, and technical requirements. Refined standards addressing timing of KRAS testing, laboratory performance and accuracy, quality assurance and control, proper tissue collection, and appropriate result reporting would also be greatly beneficial. Pathologists should be aware that the amount of information they need to manage will increase, because future trends and technological advances will enhance the predictive power of diagnostic tests or the scope of the biomarker panels tested routinely across tumor types.

  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. 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.

  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...... PIUS-findings at the same session. A total of 30 patients with known or clinically suspected cancer underwent conventional B-mode scanning and PIUS with IV-administered contrast agent. The number of liver metastases in the right and the left liver lobe, respectively, was recorded. All patients...... findings were performed in 17 of 18 patients. All biopsies of additional findings confirmed malignancy. PIUS with an IV contrast agent increased the ability to detect liver metastases compared to conventional US scanning. The technique had a high impact on patient management. The results showed that PIUS...

  20. 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

    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...

  1. 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.

  2. c-Raf in KRas Mutant Cancers: A Moving Target.

    Science.gov (United States)

    McCormick, Frank

    2018-02-12

    Therapies for KRas cancers remain a major clinical need. In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRas G12V /Trp53 tumors, without obvious systemic toxicity and without affecting MAPK signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Detection of active intraabdominal hemorrhage after blunt trauma: value of delayed CT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Sivit, C.J. [Department of Radiology, Rainbow Babies and Children' s Hospital of the University Hospitals of Cleveland and Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH (United States)

    2000-02-01

    Active hemorrhage is a rare finding at CT following blunt abdominal trauma. The time interval between IV contrast administration and scanning the abdomen may impact on the ability to visualize active hemorrhage at CT. We report a case of active hemorrhage associated with splenic injury that was identified only at delayed CT scanning. (orig.)

  4. Detection of active intraabdominal hemorrhage after blunt trauma: value of delayed CT scanning

    International Nuclear Information System (INIS)

    Sivit, C.J.

    2000-01-01

    Active hemorrhage is a rare finding at CT following blunt abdominal trauma. The time interval between IV contrast administration and scanning the abdomen may impact on the ability to visualize active hemorrhage at CT. We report a case of active hemorrhage associated with splenic injury that was identified only at delayed CT scanning. (orig.)

  5. Scanning Laser Polarimetry and Optical Coherence Tomography for Detection of Retinal Nerve Fiber Layer Defects

    Science.gov (United States)

    Oh, Jong-Hyun

    2009-01-01

    Purpose 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. Methods 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. Results 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. Conclusions 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. PMID:19794943

  6. Detection of Aspens Using High Resolution Aerial Laser Scanning Data and Digital Aerial Images

    Directory of Open Access Journals (Sweden)

    Kalle Eerikäinen

    2008-08-01

    Full Text Available The aim was to use high resolution Aerial Laser Scanning (ALS data and aerial images to detect European aspen (Populus tremula L. from among other deciduous trees. The field data consisted of 14 sample plots of 30 m × 30 m size located in the Koli National Park in the North Karelia, Eastern Finland. A Canopy Height Model (CHM was interpolated from the ALS data with a pulse density of 3.86/m2, low-pass filtered using Height-Based Filtering (HBF and binarized to create the mask needed to separate the ground pixels from the canopy pixels within individual areas. Watershed segmentation was applied to the low-pass filtered CHM in order to create preliminary canopy segments, from which the non-canopy elements were extracted to obtain the final canopy segmentation, i.e. the ground mask was analysed against the canopy mask. A manual classification of aerial images was employed to separate the canopy segments of deciduous trees from those of coniferous trees. Finally, linear discriminant analysis was applied to the correctly classified canopy segments of deciduous trees to classify them into segments belonging to aspen and those belonging to other deciduous trees. The independent variables used in the classification were obtained from the first pulse ALS point data. The accuracy of discrimination between aspen and other deciduous trees was 78.6%. The independent variables in the classification function were the proportion of vegetation hits, the standard deviation of in pulse heights, accumulated intensity at the 90th percentile and the proportion of laser points reflected at the 60th height percentile. The accuracy of classification corresponded to the validation results of earlier ALS-based studies on the classification of individual deciduous trees to tree species.

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

    International Nuclear Information System (INIS)

    Weis, Christoph D.

    2011-01-01

    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.

  8. Spiral CT scanning technique in the detection of aspiration of LEGO foreign bodies

    International Nuclear Information System (INIS)

    Applegate, K.E.; Dardinger, J.T.; Herts, B.R.; Davros, W.J.; Obuchowski, N.A.; Lieber, M.L.; Maneker, A.

    2001-01-01

    Background:. Radiolucent foreign bodies (FBs) such as plastic objects and toys remain difficult to identify on conventional radiographs of the neck and chest. Children may present with a variety of respiratory complaints, which may or may not be due to a FB. Objective: To determine whether radiolucent FBs such as plastic LEGOs and peanuts can be seen in the tracheobronchial tree or esophagus using low-dose spiral CT, and, if visible, to determine the optimal CT imaging technique. Materials and methods: Multiple spiral sequences were performed while varying the CT parameters and the presence and location of FBs in either the trachea or the esophagus first on a neck phantom and then a cadaver. Sequences were rated by three radiologists blinded to the presence of a FB using a single scoring system. Results: The LEGO was well visualized in the trachea by all three readers (both lung and soft-tissue windowing: combined sensitivity 89 %, combined specificity 89 %) and to a lesser extent in the esophagus (combined sensitivity 31 %, combined specificity 100 %). The peanut was not well visualized (combined sensitivity < 35 %). The optimal technique for visualizing the LEGO was 120 kV, 90 mA, 3-mm collimation, 0.75 s/revolution, and 2.0 pitch. This allowed for coverage of the cadaver tracheobronchial tree (approximately 11 cm) in about 18 s. Although statistical power was low for detecting significant differences, all three readers noted higher average confidence ratings with lung windowing among 18 LEGO-in-trachea scans. Conclusion: Rapid, low-dose spiral CT may be used to visualize LEGO FBs in the airway or esophagus. Peanuts were not well visualized. (orig.)

  9. Spiral CT scanning technique in the detection of aspiration of LEGO foreign bodies.

    Science.gov (United States)

    Applegate, K E; Dardinger, J T; Lieber, M L; Herts, B R; Davros, W J; Obuchowski, N A; Maneker, A

    2001-12-01

    Radiolucent foreign bodies (FBs) such as plastic objects and toys remain difficult to identify on conventional radiographs of the neck and chest. Children may present with a variety of respiratory complaints, which may or may not be due to a FB. To determine whether radiolucent FBs such as plastic LEGOs and peanuts can be seen in the tracheobronchial tree or esophagus using low-dose spiral CT, and, if visible, to determine the optimal CT imaging technique. Multiple spiral sequences were performed while varying the CT parameters and the presence and location of FBs in either the trachea or the esophagus first on a neck phantom and then a cadaver. Sequences were rated by three radiologists blinded to the presence of a FB using a single scoring system. The LEGO was well visualized in the trachea by all three readers (both lung and soft-tissue windowing: combined sensitivity 89 %, combined specificity 89 %) and to a lesser extent in the esophagus (combined sensitivity 31 %, combined specificity 100 %). The peanut was not well visualized (combined sensitivity LEGO was 120 kV, 90 mA, 3-mm collimation, 0.75 s/revolution, and 2.0 pitch. This allowed for coverage of the cadaver tracheobronchial tree (approximately 11 cm) in about 18 s. Although statistical power was low for detecting significant differences, all three readers noted higher average confidence ratings with lung windowing among 18 LEGO-in-trachea scans. Rapid, low-dose spiral CT may be used to visualize LEGO FBs in the airway or esophagus. Peanuts were not well visualized.

  10. 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

  11. 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.

  12. Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

    Science.gov (United States)

    Wang, Xiao-Song; Shankar, Sunita; Dhanasekaran, Saravana M.; Ateeq, Bushra; Sasaki, Atsuo T.; Jing, Xiaojun; Robinson, Daniel; Cao, Qi; Prensner, John R.; Yocum, Anastasia K.; Wang, Rui; Fries, Daniel F.; Han, Bo; Asangani, Irfan A.; Cao, Xuhong; Li, Yong; Omenn, Gilbert S.; Pflueger, Dorothee; Gopalan, Anuradha; Reuter, Victor E.; Kahoud, Emily Rose; Cantley, Lewis C.; Rubin, Mark A.; Palanisamy, Nallasivam; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

    2011-01-01

    Using an integrative genomics approach called Amplification Breakpoint Ranking and Assembly (ABRA) analysis, we nominated KRAS as a gene fusion with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line, originally derived from prostate cancer metastasis to the brain. Interestingly, analysis of tissues revealed that 2 of 62 metastatic prostate cancers harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, specific knock-down of which, attenuates cell invasion and xenograft growth. Ectopic expression of the UBE2L3-KRAS fusion protein exhibits transforming activity in NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly engaged by oncogenic mutant KRAS, and instead signals via AKT and p38 MAPK pathways. This is the first report of a gene fusion involving Ras family suggesting that this aberration may drive metastatic progression in a rare subset of prostate cancers. PMID:22140652

  13. 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

  14. 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.

  15. Analysis of the K-ras and p53 pathways in x-ray-induced lung tumors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Middleton, S.K.; Hahn, F.F.; Nikula, K.J. [Inhalation Toxicology Research Inst., Albuquerque, NM (United States); Picksley, S.M. [Medical Sciences Inst., Dundee (United Kingdom)

    1996-04-01

    The risk from exposure to low-dose radiation in conjunction with cigarette smoking has not been estimated due in part to lmited knowledge surrounding the molecular mechanisms underlying radiation-induced cancers. The purpose of this investigation was to determine the frequency for alterations in genes within the K-ras and p53 signal and cell cycle regulatory pathways, respectively, in X-ray-induced lung tumors in the F344/N rat. These tumors were examined for genetic alterations in the K-ras, c-raf-1, p53, mdm2 and cip1 genes. No K-ras mutations were detected by sequencing in 18 squamous cell carcinomas (SCCs) or 17 adenocarcinomas. However, using a K-ras codon 12 mutation selection assay, a codon 12 GGT {r_arrow} GAT mutation was detected in one SCC, suggesting that activation of the K-ras proto-oncogene is both a rare and late event. Single-strand conformation polymorphism (SSCP) analysis of the kinase-binding domain of the c-raf-1 gene did not detect any polymorphisms. Three of 18 SCCs but none of the adenocarcinomas showed p53 nuclear immunoreactivity. Single-strand conformation polymorphism analysis of exons 4-9 of the p53 gene detected only an exon 9 mutation in one SCC. Mutations were not detected in the three SCCs with immunoreactive p53 protein. No amplification of the mdm2 gene was detected; however, nuclear mdm2 immunoreactivity was present in one of the three SCCs that stained positive for the p53 protein. The complete cDNA of the rat cip1 gene comprising 810 bases was cloned and sequenced. The frequency of somatic mutations in exon 2 of the cip1 gene was determined by SSCP analysis. No alterations in electrophoretic mobility were detected. The results of this investigation indicate that alterations in the K-ras and p53 pathways do not play a major role in the genesis of X-ray-induced lung tumors in the rat. 49 refs., 5 figs.

  16. Using YOLO based deep learning network for real time detection and localization of lung nodules from low dose CT scans

    Science.gov (United States)

    Ramachandran S., Sindhu; George, Jose; Skaria, Shibon; V. V., Varun

    2018-02-01

    Lung cancer is the leading cause of cancer related deaths in the world. The survival rate can be improved if the presence of lung nodules are detected early. This has also led to more focus being given to computer aided detection (CAD) and diagnosis of lung nodules. The arbitrariness of shape, size and texture of lung nodules is a challenge to be faced when developing these detection systems. In the proposed work we use convolutional neural networks to learn the features for nodule detection, replacing the traditional method of handcrafting features like geometric shape or texture. Our network uses the DetectNet architecture based on YOLO (You Only Look Once) to detect the nodules in CT scans of lung. In this architecture, object detection is treated as a regression problem with a single convolutional network simultaneously predicting multiple bounding boxes and class probabilities for those boxes. By performing training using chest CT scans from Lung Image Database Consortium (LIDC), NVIDIA DIGITS and Caffe deep learning framework, we show that nodule detection using this single neural network can result in reasonably low false positive rates with high sensitivity and precision.

  17. Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan

    International Nuclear Information System (INIS)

    Kim, Seung Tae; Ahn, Tae Jin; Lee, Eunjin; Do, In-Gu; Lee, Su Jin; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Kim, Suk Hyeong; Lee, Jeeyun; Kim, Hee Cheol

    2015-01-01

    More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC. We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes. BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS. The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC

  18. 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.

  19. Bone position emission tomography with or without CT Is more accurate than bone scan for detection of bone metastasis

    International Nuclear Information System (INIS)

    Lee, Soo Jin; Lee, Wom Woo; Kim, Sang Eun

    2013-01-01

    Na1 8F bone positron emission tomography (bone PET) is a new imaging modality which is useful for the evaluation of bone diseases. Here, we compared the diagnostic accuracies between bone PET and bone scan for the detection of bone metastasis (BM). Sixteen cancer patients (M:F = 10:6, mean age = 60 ± 12 years) who underwent both bone PET and bone scan were analyzed. Bone PET was conducted 30 minutes after the injection of 370 MBq Na1 8F , and a bone scan was performed 3 hours after the injection of 1295 MBq 9 9mT c-hydroxymethylene diphosphonate. In the patient-based analysis (8 patients with BM and 8 without BM), the sensitivities of bone PET (100% 8/8) and bone scan (87.5% = 7/8) were not significantly different (p > 0.05), whereas the specificity of bone PET (87.5% = 7/8) was significantly greater than that of the bone scan (25% = 2/8) (p 8F bone PET is more accurate than bone scan for BM evaluation.

  20. High Definition Colonoscopy Combined with i-SCAN Imaging Technology Is Superior in the Detection of Adenomas and Advanced Lesions Compared to High Definition Colonoscopy Alone.

    Science.gov (United States)

    Bowman, Erik A; Pfau, Patrick R; Mitra, Arnab; Reichelderfer, Mark; Gopal, Deepak V; Hall, Benjamin S; Benson, Mark E

    2015-01-01

    Background. Improved detection of adenomatous polyps using i-SCAN has mixed results in small studies. Utility of i-SCAN as a primary surveillance modality for colorectal cancer screening during colonoscopy is uncertain. Aim. Comparing high definition white light endoscopy (HDWLE) to i-SCAN in their ability to detect adenomas during colonoscopy. Methods. Prospective cohort study of 1936 average risk patients who had a screening colonoscopy at an ambulatory procedure center. Patients underwent colonoscopy with high definition white light endoscopy withdrawal versus i-SCAN withdrawal during endoscopic screening exam. Primary outcome measurement was adenoma detection rate for i-SCAN versus high definition white light endoscopy. Secondary measurements included polyp size, pathology, and morphology. Results. 1007 patients underwent colonoscopy with i-SCAN and 929 with HDWLE. 618 adenomas were detected in the i-SCAN group compared to 402 in the HDWLE group (p definition white light endoscopy.

  1. Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene.

    Science.gov (United States)

    Mariani, Sara; Bertero, Luca; Osella-Abate, Simona; Di Bello, Cristiana; Francia di Celle, Paola; Coppola, Vittoria; Sapino, Anna; Cassoni, Paola; Marchiò, Caterina

    2017-07-25

    Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (127/240) of tumours, while BRAF codon 600 mutations reached 5% (12/240). Fast COLD-PCR found extra mutations at KRAS exon 2 in 15/166 (9%) of samples, previously diagnosed by Sequenom as wild-type or mutated at RAS (exons 3-4) or BRAF genes. After UDG digestion results were reproduced in 2/12 analysable subclonally mutated samples leading to a frequency of true subclonal KRAS mutations of 1.2% (2.1% of the previous Sequenom wild-type subgroup). In 10 out of 12 samples, the subclonal KRAS mutations disappeared (9 out of 12) or turned to a different sequence variant (1 out of 12). mCRC can harbour coexisting multiple gene mutations. High sensitivity assays allow the detection of a small subset of patients harbouring true subclonal KRAS mutations. However, DNA changes with mutant allele frequencies <3% detected in formalin-fixed paraffin-embedded samples may be artifactual in a non-negligible fraction of cases. UDG pre-treatment of DNA is mandatory to identify true DNA changes in archival samples and avoid misinterpretation due to artifacts.

  2. 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

  3. Quantitative detection of gold nanoparticles on individual, unstained cancer cells by scanning electron microscopy

    NARCIS (Netherlands)

    Hartsuiker, L.; van Es, P.; Petersen, W.; van Leeuwen, T. G.; Terstappen, L. W. M. M.; Otto, C.

    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

  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 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.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.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.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. 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)

    Blons, Hélène; Rouleau, Etienne; Charrier, Nathanaël; 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

    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. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    Rems Miran

    2009-08-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  7. Comparison of HER2 gene amplification and KRAS alteration in eyelid sebaceous carcinomas with that in other eyelid tumors.

    Science.gov (United States)

    Kwon, Mi Jung; Shin, Hyung Sik; Nam, Eun Sook; Cho, Seong Jin; Lee, Min Joung; Lee, Samuel; Park, Hye-Rim

    2015-05-01

    Eyelid sebaceous carcinoma (SC) represents a highly aggressive malignancy. Despite the poor prognosis, genetic alterations as potential molecular targets are not available. KRAS mutation and HER2 gene amplification may be candidates related to their genetic alterations. We examined the HER2 and KRAS alteration status in eyelid SCs and compared it with that in other eyelid tumors. The controversial topics of the human papillomavirus (HPV) and p16 expression were also investigated. HER2 amplification was determined by silver in situ hybridization, while immunohistochemistry was performed to study protein expressions in 14 SCs and controls, including 23 other eyelid malignancies and 14 benign tumors. Peptide nucleic acid-mediated PCR clamping and direct sequencing were used to detect KRAS mutations. HER2 protein overexpression was observed in 85.7% (12/14) of the SCs, of which two-thirds showed HER2 gene amplification. HER2 protein overexpression and HER2 amplification were found more frequently in eyelid SCs than in other eyelid tumors. All SCs harbored wild type KRAS genes. No HPV infections were identified in the SCs. Nevertheless, p16 overexpression was found in 71.4% (10/14) of SCs, irrespective of the status of HPV infection. Furthermore, p16 overexpression in eyelid SCs was also significantly higher than that in other eyelid tumors. HER2 protein overexpression, HER2 gene amplifications, and wild type KRAS genes are common in eyelid SCs. HER2 gene amplification may represent potential therapeutic targets for the treatment of eyelid SCs. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. A case of multiple hepatic abscesses detected by CT scan in the patient with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Saburi, Yoshio; Shuto, Ryusuke; Mizutani, Ryoko; Hosokawa, Takafumi; Itoga, Takashi

    1983-01-01

    A 34 years old man admitted to a hospital on 21 Feb. 1983 and was diagnosed acute lymphoblastic leukemia. A hematological complete remission was achieved by combination therapy of vincristine, prednisolone and L-asparaginase. However, he had complaining of high fever and right hypochondralgia since early in Apr. 1983, and it was revealed that elevation of right diaphragm on chest X-ray. Therefore, he was also given several antibiotics (CPZ, TOB, LMOX, PIPC, LCM, AMK, MINO and GM) for complication of probable liver abscess. Remittent fever was persisted in spite of as mentioned above various antibiotics. The multiple hepatic abscesses were found by CT scan of the mid-abdomen as the low density lesions, but bacterial cultures detected no any pathogens. His complaining of remittent fever and right hypochondralgia were improved by treated with Miconazole during about one month, and decreasing in size and number of multiple hepatic abscesses were found by CT scan. Though we could not determined clearly, but suspected that, multiple hepatic abscesses were due to fungus infection, by reason of therapeutic result. Regarding the complication of hepatic abscesses with leukemia, 5 cases have been reported in Japan, and one case out of 5 cases were detected by CT scan. We thought that CT scan were useful procedure for a early diagnosis of hepatic abscesses. In recently, the patient has continued of complete remission hematologically. (author)

  9. Neurolymphomatosis detected by 18F-FDG PET/CT scan - a case report

    International Nuclear Information System (INIS)

    Czepczynski, R.; Guzikowska-Ruszkowska, I.; Sowinski, J.

    2008-01-01

    Lymphoma involvement of the peripheral nerves is a rare clinical presentation of non-Hodgkin lymphoma. We report the case of a 59-year-old woman with the defect of peripheral motor neuron admitted for PET/CT scan. The scan disclosed increased 18 F-FDG activity along the brachial and lumbar plexuses together with very intense 18 F-FDG uptake in the cervical lymph node masses. The diagnosis, based on the subsequent histopathologic lymph node examination, was diffuse large B-cell lymphoma. (authors)

  10. 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.

  11. 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.

  12. Optical detection of ballistic electrons injected by a scanning-tunneling microscope

    NARCIS (Netherlands)

    Kemerink, M.; Sauthoff, K.; Koenraad, P.M.; Gerritsen, J.W.; Kempen, van H.; Wolter, J.H.

    2001-01-01

    We demonstrate a spectroscopic technique which is based on ballistic injection of minority carriers from the tip of a scanning-tunneling microscope into a semiconductor heterostructure. By analyzing the resulting electroluminescence spectrum as a function of tip-sample bias, both the injection

  13. Single molecule detection on the cell membrane with Near-field Scanning Optical Microscopy

    NARCIS (Netherlands)

    de Bakker, B.I.

    2004-01-01

    In this research we have developed a dedicated near- field scanning optical microscope (NSOM) for molecular biology and applied it to study the spatial organization of (fluorescently labeled) proteins at the cell surface. For the first time, protein clusters and individual molecules are resolved at

  14. Simple and efficient scanning tunneling luminescence detection at low-temperature

    NARCIS (Netherlands)

    Keizer, J.G.; Garleff, J.K.; Koenraad, P.M.

    2009-01-01

    We have designed and built an optical system to collect light that is generated in the tunneling region of a low-temperature scanning tunneling microscope. The optical system consists of an in situ lens placed approximately 1.5 cm from the tunneling region and an ex situ optical lens system to

  15. 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

  16. 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

  17. Scan direction induced charging dynamics and the application for detection of gate to S/D shorts in logic devices

    Science.gov (United States)

    Lei, Ming; Tian, Qing; Wu, Kevin; Zhao, Yan

    2016-03-01

    Gate to source/drain (S/D) short is the most common and detrimental failure mechanism for advanced process technology development in Metal-Oxide-Semiconductor-Field-Effect-Transistor (MOSFET) device manufacturing. Especially for sub-1Xnm nodes, MOSFET device is more vulnerable to gate-S/D shorts due to the aggressive scaling. The detection of this kind of electrical short defect is always challenging for in-line electron beam inspection (EBI), especially new shorting mechanisms on atomic scale due to new material/process flow implementation. The second challenge comes from the characterization of the shorts including identification of the exact shorting location. In this paper, we demonstrate unique scan direction induced charging dynamics (SDCD) phenomenon which stems from the transistor level response from EBI scan at post metal contact chemical-mechanical planarization (CMP) layers. We found that SDCD effect is exceptionally useful for gate-S/D short induced voltage contrast (VC) defect detection, especially for identification of shorting locations. The unique SDCD effect signatures of gate-S/D shorts can be used as fingerprint for ground true shorting defect detection. Correlation with other characterization methods on the same defective location from EBI scan shows consistent results from various shorting mechanism. A practical work flow to implement the application of SDCD effect for in-line EBI monitor of critical gate-S/D short defects is also proposed, together with examples of successful application use cases which mostly focus on static random-access memory (SRAM) array regions. Although the capability of gate-S/D short detection as well as expected device response is limited to passing transistors and pull-down transistors due to the design restriction from standard 6-cell SRAM structure, SDCD effect is proven to be very effective for gate-S/D short induced VC defect detection as well as yield learning for advanced technology development.

  18. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis

    DEFF Research Database (Denmark)

    Tran, Phuoc T; Shroff, Emelyn H; Burns, Timothy F

    2012-01-01

    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...

  19. Evaluation and identification of factors related to KRAS and BRAF gene mutations in colorectal cancer: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Li Lin

    2016-01-01

    Conclusion: The meta-analysis reveals that KRAS has a slightly higher mutation rate in MSI-L/MSS tumors. Moreover, BRAF mutations have higher detection rates in right-sided colorectal cancer, which suggests that BRAF mutations are likely in CIMP-H tumors. Therefore, based on these findings, the molecular diagnostic tests to be conducted in colorectal cancer patients can be determined according to the location/clinical features of the tumor.

  20. [Molecular beacon based PNA-FISH method combined with fluorescence scanning for rapid detection of Listeria monocytogenes].

    Science.gov (United States)

    Wu, Shan; Zhang, Xiaofeng; Shuai, Jiangbing; Li, Ke; Yu, Huizhen; Jin, Chenchen

    2016-07-04

    To simplify the PNA-FISH (Peptide nucleic acid-fluorescence in situ hybridization) test, molecular beacon based PNA probe combined with fluorescence scanning detection technology was applied to replace the original microscope observation to detect Listeria monocytogenes The 5′ end and 3′ end of the L. monocytogenes specific PNA probes were labeled with the fluorescent group and the quenching group respectively, to form a molecular beacon based PNA probe. When PNA probe used for fluorescence scanning and N1 treatment as the control, the false positive rate was 11.4%, and the false negative rate was 0; when N2 treatment as the control, the false positive rate decreased to 4.3%, but the false negative rate rose to 18.6%. When beacon based PNA probe used for fluorescence scanning, taken N1 treatment as blank control, the false positive rate was 8.6%, and the false negative rate was 1.4%; taken N2 treatment as blank control, the false positive rate was 5.7%, and the false negative rate was 1.4%. Compared with PNA probe, molecular beacon based PNA probe can effectively reduce false positives and false negatives. The success rates of hybridization of the two PNA probes were 83.3% and 95.2% respectively; and the rates of the two beacon based PNA probes were 91.7% and 90.5% respectively, which indicated that labeling the both ends of the PNA probe dose not decrease the hybridization rate with the target bacteria. The combination of liquid phase PNA-FISH and fluorescence scanning method, can significantly improve the detection efficiency.

  1. High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy.

    Science.gov (United States)

    Penny, Hugo A; Mooney, Peter D; Burden, Mitchell; Patel, Nisha; Johnston, Alexander J; Wong, Simon H; Teare, Julian; Sanders, David S

    2016-06-01

    Celiac disease remains underdiagnosed at endoscopy. We aimed to assess the utility of I-Scan (virtual chromo-endoscopy) to improve sensitivity of endoscopy to detect markers of villous atrophy in this condition. Patients from 2 UK hospitals were studied in 3 groups. Group 1: standard high definition, white light endoscopy (WLE); Group 2: WLE plus I-Scan; Group 3: non-high definition control group. The presence of endoscopic markers was recorded. At least 4 duodenal biopsies were taken from all patients. Serology was performed concurrently and observations were compared with histology. 758 patients (62% female, mean age 52) were recruited (Group 1: 230; Group 2: 228; Group 3: 300). 135 (17.8%) new diagnoses of coeliac disease were made (21 Group 1; 24 Group 2; 89 Group 3). The sensitivity for detection of endoscopic markers of villous atrophy was significantly higher in both Group 1 (85.7%, p=0.0004) and Group 2 (75%, p=0.005) compared to non-high definition controls (41.6%). There was no significant difference between high definition only and I-Scan groups (p=0.47). In non-high definition endoscopy a missed diagnosis was associated with lesser degrees of villous atrophy (p=0.019) and low tTG titre (p=0.007). High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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% [fr

  3. Personalized treatment for advanced colorectal cancer: KRAS and beyond

    International Nuclear Information System (INIS)

    Patel, Gargi Surendra; Karapetis, Christos S

    2013-01-01

    Targeted therapies have improved the survival of patients with advanced colorectal cancer (CRC). However, further improvements in patient outcomes may be gained by the development of predictive biomarkers in order to select individuals who are most likely to benefit from treatment, thus personalizing treatment. Using the epidermal growth-factor receptor (EGFR) pathway, we discuss the existing and potential predictive biomarkers in clinical development for use with EGFR-targeted agents in metastatic CRC. The data and technological issues surrounding such biomarkers as expression of EGFR or its family members or ligands, KRAS-, NRAS-, and BRAF-mutation status, PI3K/PTEN expression, and imaging and clinical biomarkers, such as rash and hypomagnesemia, are summarized. Although the discovery of KRAS mutations has improved patient selection for EGFR-targeted treatments, further biomarkers are required, especially for those patients who exhibit KRAS mutations rather than the wild-type gene

  4. Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

    Science.gov (United States)

    Joshi, Bishnu P.; Miller, Sharon J.; Lee, Cameron; Gustad, Adam; Seibel, Eric J.; Wang, Thomas D.

    2012-02-01

    We demonstrate a multi-spectral scanning fiber endoscope (SFE) that collects fluorescence images in vivo from three target peptides that bind specifically to murine colonic adenomas. This ultrathin endoscope was demonstrated in a genetically engineered mouse model of spontaneous colorectal adenomas based on somatic Apc (adenomatous polyposis coli) gene inactivation. The SFE delivers excitation at 440, 532, 635 nm with human patients by simultaneously visualizing multiple over expressed molecular targets unique to dysplasia.

  5. Leptomeningeal angiomatosis of the left occipital surface detected by CT scan

    International Nuclear Information System (INIS)

    Niiro, Masaki; Mihara, Tadahiro; Maeda, Yoshiki; Awa, Hiroshi; Kadota, Koki; Asakura, Tetsuhiko

    1982-01-01

    A case of left occipital leptomeningeal angiomatosis was reported. The patient was a 12-year-old boy who had episodes of severe vascular type headache accompanied by transient right homonymous hemianopsia. CT scan showed localized superficial high density area in the left occipital pole. Remarkable enhancement of the lower and inner surface of the left occipital lobe was demonstrated. Angiography showed poor filling of the distal portion of the left posterior cerebral artery. Skull tomograms showed linear calcifications in the left occipital region. Brain scan showed increased RI uptake in the left occipital region. During operation, the surface of the left occipital lobe was covered by excessive, fine, vascular networks which extended over the arachnoid membrane. The abnormal vessels were cauterized by a CO 2 laser as throughly as possible. The occipital pole, felt gritty. Histologically, the abnormal vessels had spread into the subarachnoid space and were predominantly veins with thin and enlarged walls. The abnormal vessels followed the leptomeninges in the sulci of the cerebral cortex. Underneath the abnormal vessels, in the external layers of the cerebral cortex, calcium deposits were scattered and gliosis and degeneration of the ganglion cells were observed. The lesion was comparable with leptomeningeal angiomatosis. Though the pathological findings of the specimen, CT findings, and brain scan findings were extremely similar to those of Sturge-Weber disease, in this case, the typical clinical and roentgenographic findings of Sturge-Weber disease were all absent. (author)

  6. Value of whole body 123I scan for detection of metastasis in patients with well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Takahashi, Naoya; Odano, Ikuo; Sugita, Tadashi; Sato, Yoko; Sakai, Kunio

    1995-01-01

    To evaluate the utility of 123 I whole body scan for detection of metastasis in patients with well-differentiated thyroid carcinoma, post-therapy whole body 131 I images in 55 cases were compared with pre-therapy 123 I images using diagnostic dose (74 MBq). The post-therapy studies were performed 7 days after administration of therapeutic doses (3.33-7.77 GBq) of 131 I. The pre-therapy scans showed 30 lesions (71.4%) of 42 lesions which were shown by 131 I post-therapy scans. The diagnostic accuracy of 123 I whole body scans was considered to be nearly the same as the images obtained by 131 I using diagnostic dose. 123 I has short-life and an optimum gamma ray energy for scintigraphy. It makes radiation dose to patients lower than that of 131 I. Therefore, we recommend pre-therapy 131 I image using diagnostic dose is replaced by 123 I image. (author)

  7. Comparison of 18F-FDG PET to CT scan in the detection of recurrent colorectal carcinoma - an ROC analysis

    International Nuclear Information System (INIS)

    Scott, A.M.; Akhurst, T.; Berlangieri, S.U.; Fitt, G.; Schelleman, T.; Jones, R.; Hannah, A.; Tochon-Danguy, H.

    2000-01-01

    Full text: This study examined 43 scans performed in 40 patients from a group of 93 prospectively enrolled in a trial examining the utility of 18 F-FDG PET in patients with potentially resectable recurrent colorectal cancer. All patients had PET and CT scans prior to surgery, where a total of 84 anatomical regions were biopsied, and 364 regions examined by the surgeons. All PET and CT scans were viewed blinded to clinical and imaging data. The scans were interpreted according to a five-point confidence scale to enable an ROC analysis to be performed. An assessment of the impact of PET over CT in patients was also made. Of the 43 cases PET and CT were concordant in 24 (56%). There were 16 cases where PET added additional diagnostic information to the benefit of the patient (37%), and three (7%) where PET alone would have lead to a potentially negative outcome. The majority of cases where PET performed better were in cases with extrahepatic disease. CT was more sensitive in the detection of pulmonary nodules, although the specificity of CT was less than PET. In conclusion, 18 F-FDG PET performed significantly better than CT both in terms of a regional analysis as well as a patient by patient basis. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  8. 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.

  9. Whole Genome Scan to Detect Chromosomal Regions Affecting Multiple Traits in Dairy Cattle

    NARCIS (Netherlands)

    Schrooten, C.; Bink, M.C.A.M.; Bovenhuis, H.

    2004-01-01

    Chromosomal regions affecting multiple traits ( multiple trait quantitative trait regions or MQR) in dairy cattle were detected using a method based on results from single trait analyses to detect quantitative trait loci (QTL). The covariance between contrasts for different traits in single trait

  10. The development of a line-scan imaging algorithm for the detection of fecal contamination on leafy geens

    Science.gov (United States)

    Yang, Chun-Chieh; Kim, Moon S.; Chuang, Yung-Kun; Lee, Hoyoung

    2013-05-01

    This paper reports the development of a multispectral algorithm, using the line-scan hyperspectral imaging system, to detect fecal contamination on leafy greens. Fresh bovine feces were applied to the surfaces of washed loose baby spinach leaves. A hyperspectral line-scan imaging system was used to acquire hyperspectral fluorescence images of the contaminated leaves. Hyperspectral image analysis resulted in the selection of the 666 nm and 688 nm wavebands for a multispectral algorithm to rapidly detect feces on leafy greens, by use of the ratio of fluorescence intensities measured at those two wavebands (666 nm over 688 nm). The algorithm successfully distinguished most of the lowly diluted fecal spots (0.05 g feces/ml water and 0.025 g feces/ml water) and some of the highly diluted spots (0.0125 g feces/ml water and 0.00625 g feces/ml water) from the clean spinach leaves. The results showed the potential of the multispectral algorithm with line-scan imaging system for application to automated food processing lines for food safety inspection of leafy green vegetables.

  11. Feasibility for detection of autofluorescent signatures in rat organs using a novel excitation-scanning hyperspectral imaging system

    Science.gov (United States)

    Favreau, Peter F.; Deal, Joshua A.; Weber, David S.; Rich, Thomas C.; Leavesley, Silas J.

    2016-04-01

    The natural fluorescence (autofluorescence) of tissues has been noted as a biomarker for cancer for several decades. Autofluorescence contrast between tumors and healthy tissues has been of significant interest in endoscopy, leading to development of autofluorescence endoscopes capable of visualizing 2-3 fluorescence emission wavelengths to achieve maximal contrast. However, tumor detection with autofluorescence endoscopes is hindered by low fluorescence signal and limited quantitative information, resulting in prolonged endoscopic procedures, prohibitive acquisition times, and reduced specificity of detection. Our lab has designed a novel excitation-scanning hyperspectral imaging system with high fluorescence signal detection, low acquisition time, and enhanced spectral discrimination. In this study, we surveyed a comprehensive set of excised tissues to assess the feasibility of detecting tissue-specific pathologies using excitation-scanning. Fresh, untreated tissue specimens were imaged from 360 to 550 nm on an inverted fluorescence microscope equipped with a set of thin-film tunable filters (Semrock, A Unit of IDEX). Images were subdivided into training and test sets. Automated endmember extraction (ENVI 5.1, Exelis) with PCA identified endmembers within training images of autofluorescence. A spectral library was created from 9 endmembers. The library was used for identification of endmembers in test images. Our results suggest (1) spectral differentiation of multiple tissue types is possible using excitation scanning; (2) shared spectra between tissue types; and (3) the ability to identify unique morphological features in disparate tissues from shared autofluorescent components. Future work will focus on isolating specific molecular signatures present in tissue spectra, and elucidating the contribution of these signatures in pathologies.

  12. Design of a surface-scanning coil detector for direct bacteria detection on food surfaces using a magnetoelastic biosensor

    Science.gov (United States)

    Chai, Yating; Wikle, Howard C.; Wang, Zhenyu; Horikawa, Shin; Best, Steve; Cheng, Zhongyang; Dyer, Dave F.; Chin, Bryan A.

    2013-09-01

    The real-time, in-situ bacteria detection on food surfaces was achieved by using a magnetoelastic biosensor combined with a surface-scanning coil detector. This paper focuses on the coil design for signal optimization. The coil was used to excite the sensor's vibration and detect its resonant frequency signal. The vibrating sensor creates a magnetic flux change around the coil, which then produces a mutual inductance. In order to enhance the signal amplitude, a theory of the sensor's mutual inductance with the measurement coil is proposed. Both theoretical calculations and experimental data showed that the working length of the coil has a significant effect on the signal amplitude. For a 1 mm-long sensor, a coil with a working length of 1.3 mm showed the best signal amplitude. The real-time detection of Salmonella bacteria on a fresh food surface was demonstrated using this new technology.

  13. Mobile gamma-ray scanning system for detecting radiation anomalies associated with 226Ra-bearing materials

    International Nuclear Information System (INIS)

    Myrick, T.E.; Blair, M.S.; Doane, R.W.; Goldsmith, W.A.

    1982-11-01

    A mobile gamma-ray scanning system has been developed by Oak Ridge National Laboratory for use in the Department of Energy's remedial action survey programs. The unit consists of a NaI(T1) detection system housed in a specially-equipped van. The system is operator controlled through an on-board mini-computer, with data output provided on the computer video screen, strip chart recorders, and an on-line printer. Data storage is provided by a floppy disk system. Multichannel analysis capabilities are included for qualitative radionuclide identification. A 226 Ra-specific algorithm is employed to identify locations containing residual radium-bearing materials. This report presents the details of the system description, software development, and scanning methods utilized with the ORNL system. Laboratory calibration and field testing have established the system sensitivity, field of view, and other performance characteristics, the results of which are also presented. Documentation of the instrumentation and computer programs are included

  14. Real time detection of antibody-antigen interaction using a laser scanning confocal imaging-surface plasmon resonance system

    International Nuclear Information System (INIS)

    Zhang Hong-Yan; Yang Li-Quan; Ning Ting-Yin; Liu Wei-Min; Sun Jia-Yu; Wang Peng-Fei; Meng Lan; Nie Jia-Cai

    2012-01-01

    A laser scanning confocal imaging-surface plasmon resonance (LSCI-SPR) instrument integrated with a wavelength-dependent surface plasmon resonance (SPR) sensor and a laser scanning confocal microscopy (LSCM) is built to detect the bonding process of human IgG and fluorescent-labeled affinity purified antibodies in real time. The shifts of resonant wavelength at different reaction time stages are obtained by SPR, corresponding well with the changes of the fluorescence intensity collected by using LSCM. The instrument shows the merits of the combination and complementation of the SPR and LSCM, with such advantages as quantificational analysis, high spatial resolution and real time monitor, which are of great importance for practical applications in biosensor and life science. (general)

  15. GMR-based eddy current probe for weld seam inspection and its non-scanning detection study

    Science.gov (United States)

    Gao, Peng; Wang, Chao; Li, Yang; Wang, Libin; Cong, Zheng; Zhi, Ya

    2017-04-01

    Eddy current testing is one of the most important non-destructive testing methods for welding defects detection. This paper presents the use of a probe consisting of 4 giant magneto-resistive (GMR) sensors to detect weld defects. Information from four measuring points above and on both sides of the weld seam is collected at the same time. By setting the GMR sensors' sensing axes perpendicular to the direction of the excitation magnetic field, the information collected mainly reflects the change in the eddy current which is caused by defects. Digital demodulation technology is applied to extract the real part and imaginary part of the GMR sensors' output signals. The variables containing directional information of the magnetic field are introduced. Based on the data from the four GMR (4-GMR) sensors' output signals, four values, Ran, Mean, Var and k are selected as the feature quantities for defect recognition. Experiments are carried out on weld seams with and without defects, and the detection outputs are given in this paper. The 4-GMR probe is also employed to investigate non-scanning weld defect detection and the four feature quantities (Ran, Mean, Var and k) are studied to evaluate weld quality. The non-scanning weld defect detection is presented. A support vector machine is used to classify and discriminate welds with and without defects. Experiments carried out show that through the method in this paper, the recognition rate is 92% for welds without defects and 90% for welds with defects, with an overall recognition rate of 90.9%, indicating that this method could effectively detect weld defects.

  16. Colonic volvulus detected by CT scan in a case with mental retardation and prune belly syndrome.

    Science.gov (United States)

    Oka, Yoichiro; Masumoto, Kouji; Nakamura, Masatoshi; Iwasaki, Akinori

    2011-10-01

    Colonic volvulus is a rare disease in children. Delayed diagnosis of the condition can often be fatal, especially in pediatric patients with mental retardation. We herein present the case of a female pediatric patient with colonic volvulus, prune belly syndrome, and mental retardation. Preoperative CT scans showed the characteristic signs of this disease. The volvulus occurred in the proximal colon of the colostomy. The release of the colonic volvulus and reconstruction of the colostomy were performed without the resection of the ischemic colon. The postoperative clinical course was uneventful. Copyright © 2012. Published by Elsevier B.V.

  17. Colonic volvulus detected by CT scan in a case with mental retardation and prune belly syndrome

    Directory of Open Access Journals (Sweden)

    Yoichiro Oka

    2011-10-01

    Full Text Available Colonic volvulus is a rare disease in children. Delayed diagnosis of the condition can often be fatal, especially in pediatric patients with mental retardation. We herein present the case of a female pediatric patient with colonic volvulus, prune belly syndrome, and mental retardation. Preoperative CT scans showed the characteristic signs of this disease. The volvulus occurred in the proximal colon of the colostomy. The release of the colonic volvulus and reconstruction of the colostomy were performed without the resection of the ischemic colon. The postoperative clinical course was uneventful.

  18. Study on thallium-201 myocardial perfusion scanning for detection of right ventricular hypertrophy in chronic pulmonary disease

    International Nuclear Information System (INIS)

    Kawai, Seiki

    1980-01-01

    Thallium-201 myocardial perfusion scanning was performed in 34 patients with chronic pulmonary disease for the purpose of detecting right ventricular hypertrophy. Thallium-201 activity ratio of left ventricle plus ventricular septum/right ventricle (TAR) was significantly correlated with hemodynamic findings such as pulmonary arterial mean pressure (r = -0.75, p 2 (p < 0.001). Assuming that TAR < 2 or TAR = 2 would indicate pulmonary hypertension, sensitivity was 95%, specificity 79%, validity score 75%, false positive 14% and false negative was 8%. TAR was compared with left to right ventricular mass ratio using Fulton's method in 6 autopsied patients in whom thallium-201 myocardial perfusion scanning were performed within three months before death. TAR closely correlated with left to right ventricular mass ratio (r = 0.978, p < 0.001). The comparison of validity of TAR with those of electrocardiographic interpretation according to WHO, Sasamoto, Roman or Milnor for the detection of right ventricular hypertrophy revealed the former was much superior to all of latters. From the results obtained, it may be inferred that TAR reflects the degree of pulmonary hypertension and anatomical right ventricular hypertrophy and is a useful non-invasive method to detect right ventricular hypertrophy in chronic pulmonary disease. (J.P.N.)

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

    International Nuclear Information System (INIS)

    Velho, Sérgia; Moutinho, Cátia; Cirnes, Luís; Albuquerque, Cristina; Hamelin, Richard; Schmitt, Fernando; Carneiro, Fátima; Oliveira, Carla; Seruca, Raquel

    2008-01-01

    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. 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. 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). 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 serrated polyps and verified that colorectal serrated

  20. 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

  1. 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.

  2. Single- and multi-frequency detection of surface displacements via scanning probe microscopy.

    Science.gov (United States)

    Romanyuk, Konstantin; Luchkin, Sergey Yu; Ivanov, Maxim; Kalinin, Arseny; Kholkin, Andrei L

    2015-02-01

    Piezoresponse force microscopy (PFM) provides a novel opportunity to detect picometer-level displacements induced by an electric field applied through a conducting tip of an atomic force microscope (AFM). Recently, it was discovered that superb vertical sensitivity provided by PFM is high enough to monitor electric-field-induced ionic displacements in solids, the technique being referred to as electrochemical strain microscopy (ESM). ESM has been implemented only in multi-frequency detection modes such as dual AC resonance tracking (DART) and band excitation, where the response is recorded within a finite frequency range, typically around the first contact resonance. In this paper, we analyze and compare signal-to-noise ratios of the conventional single-frequency method with multi-frequency regimes of measuring surface displacements. Single-frequency detection ESM is demonstrated using a commercial AFM.

  3. Detection of acute inflammatory bowel disease with Tc-99m-HSA-sucralfate scans

    International Nuclear Information System (INIS)

    Yip, T.C.; Houle, S.; Jeejeebhoy, K.N.

    1987-01-01

    Sucralfate binds to mucosal ulcerations. Twelve studies were performed in 11 patients with inflammatory bowel disease. Technetium-sucralfate was prepared in vitro and given orally. Images were obtained at 4-6, 24, and 48 hours. Persistent focal abnormalities or activity in the large bowel beyond 48 hours was interpreted as positive. Patients' charts were reviewed. Technetium-sucralfate was positive in ten of ten studies in nine patients with active disease, one with equivocal activity, and negative in one patient with inactive disease. Nine of 19 abnormal sites were detected with technetium-sucralfate and radiology or endoscopy; six of ten were detected with technetium-sucralfate only. Technetium-sucralfate is very sensitive in detecting active inflammatory bowel disease in individual patients

  4. Scanning Electron Microscope Mapping System Developed for Detecting Surface Defects in Fatigue Specimens

    Science.gov (United States)

    Bonacuse, Peter J.; Kantzos, Peter T.

    2002-01-01

    An automated two-degree-of-freedom specimen positioning stage has been developed at the NASA Glenn Research Center to map and monitor defects in fatigue specimens. This system expedites the examination of the entire gauge section of fatigue specimens so that defects can be found using scanning electron microscopy (SEM). Translation and rotation stages are driven by microprocessor-based controllers that are, in turn, interfaced to a computer running custom-designed software. This system is currently being used to find and record the location of ceramic inclusions in powder metallurgy materials. The mapped inclusions are periodically examined during interrupted fatigue experiments. The number of cycles to initiate cracks from these inclusions and the rate of growth of initiated cracks can then be quantified. This information is necessary to quantify the effect of this type of defect on the durability of powder metallurgy materials. This system was developed with support of the Ultra Safe program.

  5. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.

    Science.gov (United States)

    Kamerkar, Sushrut; LeBleu, Valerie S; Sugimoto, Hikaru; Yang, Sujuan; Ruivo, Carolina F; Melo, Sonia A; Lee, J Jack; Kalluri, Raghu

    2017-06-22

    The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras G12D , a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.

  6. FabryScan: a screening tool for early detection of Fabry disease

    NARCIS (Netherlands)

    Arning, Kathrin; Naleschinski, Dennis; Maag, Rainer; Biegstraaten, Marieke; Kropp, Peter; Lorenzen, Jürgen; Hollak, Carla E. M.; van Schaik, Ivo N.; Harten, Pontus; Zeuner, Rainald A.; Binder, Andreas; Baron, Ralf

    2012-01-01

    Fabry disease, an X-linked lipid storage disorder, is associated early morbidity and mortality. Since enzyme replacement therapy is available, accurate detection of unrecognized cases is important. Characteristic early symptoms are recurrent episodes of burning and lancinating pain in the distal

  7. Detection of defects in logs using computer assisted tomography (CAT) scanning

    International Nuclear Information System (INIS)

    Tonner, P.D.; Lupton, L.R.

    1985-01-01

    The Chalk River Nuclear Laboratories of AECL have performed a preliminary feasibility study on the applicability of computer assisted tomographic techniques to detect the internal structure of logs. Cross sections of three logs have been obtained using a medical CAT scanner. The results show that knots, rot and growth rings are easily recognized in both dry and wet logs

  8. Computer aided detection system for lung cancer using computer tomography scans

    Science.gov (United States)

    Mahesh, Shanthi; Rakesh, Spoorthi; Patil, Vidya C.

    2018-04-01

    Lung Cancer is a disease can be defined as uncontrolled cell growth in tissues of the lung. If we detect the Lung Cancer in its early stage, then that could be the key of its cure. In this work the non-invasive methods are studied for assisting in nodule detection. It supplies a Computer Aided Diagnosis System (CAD) for early detection of lung cancer nodules from the Computer Tomography (CT) images. CAD system is the one which helps to improve the diagnostic performance of radiologists in their image interpretations. The main aim of this technique is to develop a CAD system for finding the lung cancer using the lung CT images and classify the nodule as Benign or Malignant. For classifying cancer cells, SVM classifier is used. Here, image processing techniques have been used to de-noise, to enhance, for segmentation and edge detection of an image is used to extract the area, perimeter and shape of nodule. The core factors of this research are Image quality and accuracy.

  9. Early detection of drug-induced pneumonitis by gallium-67 lung scan in six patients with normal chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, H; Sawa, H; Takashima, S [Osaka City Univ. (Japan). Hospital

    1981-06-01

    Increased pulmonary accumulation of Gallium-67-citrate was observed in 6 patients (4 with malignant lymphoma, 1 with uterine cancer and 1 with acute myelocytic leukemia) preceding the appearance of any abnormal findings in both chest X-ray and blood gas data. All of them had received multiple courses of chemotherapy. In these patients, the anticancer drugs were administered for 13 to 22 weeks (mean 15 weeks). One patient with malignant lymphoma showed abnormal /sup 67/Ga lung uptake greater than hepatic activity, 3 patients (malignant lymphoma, 2 and uterine cancer, 1) visualized abnormal /sup 67/Ga lung uptake equal to hepatic activity and 2 cases (malignant lymphoma, 1 and acute myelocytic leukemia, 1) demonstrated abnormal accumulation of /sup 67/Ga in the lung greater than background activity. In 4 patients (3 with malignant lymphoma and 1 with uterine cancer) out of 6, transbronchial lung biopsy obtained after the /sup 67/Ga scans showed non-specific interstitial pneumonitis with infiltration of lymphocytes and macrophages compatible with drug-induced pneumonitis. In the other 2 patients, cytology and cultures were negative and follow up /sup 67/Ga lung scans revealed a reduction in intensity of uptake after treatment with corticosteroid. Therefore, we considered that the /sup 67/Ga lung scan was useful for early detection of drug-induced pneumonitis.

  10. Role of stress myocardial perfusion SPECT scan in detection and management of coronary artery disease: Nairobi experience

    International Nuclear Information System (INIS)

    Makhdomi, K.B.; Warshow, M.M.; Patel, P.K.J.; Shah, D.; Githegi, D.R.M.

    2002-01-01

    Aim: Stress myocardial perfusion scans have acquired a significant role in the detection and management of Coronary Artery Disease. However, this mode of investigation has only recently been available in Nairobi, and this is the first such study from East Africa. We undertook a comparison of our results with that in the literature, to see whether they conformed to it. Materials and Methods: We performed a review of our initial 82 evaluable studies. The scans were performed with 99mTc-Tetrofosmin, using the single day stress-rest protocol with SPECT acquisitions. We carried out a correlation of our scan findings with angiographic data (where available), and clinical follow-up. The clinical end points where furnished by the referring physicians. We focused on myocardial infarction, need for re-vascularisation, and death. The mean clinical follow-up was 21.8 months (range of 12 months to 39 months). Results: Eighty (98%) of the studies revealed concordance with angiographic findings and/or were predictive of clinical outcome. Two studies were discordant, and will be discussed. The results are comparable with those in the literature. Conclusion: It is concluded that stress myocardial perfusion studies, done at our Centre, had a good predictive value, with regards to the presence and severity of disease, and correlated with the clinical outcome data

  11. Fuzzy-neural network in the automatic detection and volumetry of the spleen on spiral CT scans

    International Nuclear Information System (INIS)

    Heitmann, K.R.; Mainz Univ.; Rueckert, S.; Heussel, C.P.; Thelen, M.; Kauczor, H.U.; Uthmann, T.

    2000-01-01

    Purpose: To assess spleen segmentation and volumetry in spiral CT scans with and without pathological changes of splenic tissue. Methods: The image analysis software HYBRIKON is based on region growing, self-organized neural nets, and fuzzy-anatomic rules. The neural nets were trained with spiral CT data from 10 patients, not used in the following evaluation on spiral CT scans from 19 patients. An experienced radiologist verified the results. The true positive and false positive areas were compared in terms to the areas marked by the radiologist. The results were compared with a standard thresholding method. Results: The neural nets achieved a higher accuracy than the thresholding method. Correlation coefficient of the fuzzy-neural nets: 0.99 (thresholding: 0.63). Mean true positive rate: 90% (thresholding: 75%), mean false positive rate: 5% (thresholding>100%). Pitfalls were caused by accessory spleens, extreme changes in the morphology (tumors, metastases, cysts), and parasplenic masses. Conclusions: Self-organizing neural nets combined with fuzzy rules are ready for use in the automatic detection and volumetry of the spleen in spiral CT scans. (orig.) [de

  12. KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis.

    Science.gov (United States)

    Westwood, Marie; van Asselt, Thea; Ramaekers, Bram; Whiting, Penny; Joore, Manuela; Armstrong, Nigel; Noake, Caro; Ross, Janine; Severens, Johan; Kleijnen, Jos

    2014-10-01

    Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost. To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone. Thirteen databases, including MEDLINE and EMBASE, research registers and conference proceedings were searched to January 2013. Additional data were obtained from an online survey of laboratories participating in the UK National External Quality Assurance Scheme pilot for KRAS mutation testing. A systematic review of the evidence was carried out using standard methods. Randomised controlled trials were assessed for quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using the QUADAS-2 tool. There were insufficient data for meta-analysis. For accuracy studies we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data were summarised as relative risks, with 95% CIs. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different tests followed by treatment

  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. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients.

    Science.gov (United States)

    Papadopoulou, Eirini; Tsoulos, Nikolaos; Tsirigoti, Angeliki; Apessos, Angela; Agiannitopoulos, Konstantinos; Metaxa-Mariatou, Vasiliki; Zarogoulidis, Konstantinos; Zarogoulidis, Pavlos; Kasarakis, Dimitrios; Kakolyris, Stylianos; Dahabreh, Jubrail; Vlastos, Fotis; Zoublios, Charalampos; Rapti, Aggeliki; Papageorgiou, Niki Georgatou; Veldekis, Dimitrios; Gaga, Mina; Aravantinos, Gerasimos; Karavasilis, Vasileios; Karagiannidis, Napoleon; Nasioulas, George

    2015-10-01

    It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor ( EGFR ) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18-21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of

  15. [Application of second generation dual-source computed tomography dual-energy scan mode in detecting pancreatic adenocarcinoma].

    Science.gov (United States)

    Xue, Hua-dan; Liu, Wei; Sun, Hao; Wang, Xuan; Chen, Yu; Su, Bai-yan; Sun, Zhao-yong; Chen, Fang; Jin, Zheng-yu

    2010-12-01

    To analyze the clinical value of multiple sequences derived from dual-source computed tomography (DSCT) dual-energy scan mode in detecting pancreatic adenocarcinoma. Totally 23 patients with clinically or pathologically diagnosed pancreatic cancer were enrolled in this retrospective study. DSCT (Definition Flash) was used and dual-energy scan mode was used in their pancreatic parenchyma phase scan (100kVp/230mAs and Sn140kVp/178mAs) . Mono-energetic 60kev, mono-energetic 80kev, mono-energetic 100kev, mono-energetic 120kev, linear blend image, non-linear blend image, and iodine map were acquired. pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were calculated. One-way ANOVA was used for the comparison of diagnostic values of the above eight different dual-energy derived sequences for pancreatic cancer. The pancreatic parenchyma-tumor CT value difference, ratio of tumor to pancreatic parenchyma, and pancreatic parenchyma-tumor contrast to noise ratio were significantly different among eight sequences (P<0.05) . Mono-energetic 60kev image showed the largest parenchyma-tumor CT value [ (77.53 ± 23.42) HU] , and iodine map showed the lowest tumor/parenchyma enhancement ratio (0.39?0.12) and the largest contrast to noise ratio (4.08 ± 1.46) . Multiple sequences can be derived from dual-energy scan mode with DSCT via multiple post-processing methods. Integration of these sequences may further improve the sensitivity of the multislice spiral CT in the diagnosis of pancreatic cancer.

  16. Frequency and significance of thoracic injuries detected on abdominal trauma CT scans

    International Nuclear Information System (INIS)

    Hareli, G.S.; Rhea, J.T.; Novelline, R.A.; Lawrason, N.; Sacknoff, R.; Oser, A.

    1987-01-01

    The authors have noted that in multiple trauma patients chest injuries inapparent on initial chest radiographs may be detected at abdominal CT. In an ongoing series of 112 patients to date, 50 chest injuries were detected in 33 patients (29%). The injuries included 15 bilateral hemothoraces, seven unilateral hemothoraces, seven posttraumatic atrelectasis, seven lung contusions, five pneumothoraces, four rib factures, two thoracic spine fractures, two chest wall emphysema, and one mediastinal emphysema. In 24 of the 33 patients (72%) the injury was not seen on the initial chest radiographs; in seven patients treatment of the chest injury was required. The authors have included screening cuts of the middle and upper chest as part of their abdominal CT protocol

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

    Science.gov (United States)

    Chen, Shuoyang; Xu, Tingfa; Li, Daqun; Zhang, Jizhou; Jiang, Shenwang

    2016-01-01

    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. PMID:27775671

  18. 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.

  19. 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...... the decay of the plasmon-field coherence. Generation of the measured signal at the tunneling junction offers the possibility to observe ultrafast effects with a spatial resolution determined by the tunneling junction...

  20. Bone Scan in Detection of Biological Activity in Nonhypertrophic Fracture Nonunion

    OpenAIRE

    Gandhi, Sunny J.; Rabadiya, Bhavdeep

    2017-01-01

    Biological activity of the fracture site is very important factor in treatment planning of fracture nonunion. If no biological activity is detected, then an autologous bone graft can be supplemented or osteogenic supplementations, such as bone morphogenetic protein is given. If biological activity is present, then secure fixation is sufficient to achieve bony union. Biological activity of nonunions is usually assessed by conventional radiographs. The presence of callus formation is usually as...

  1. Anteroposterior chest radiograph vs. chest CT scan in early detection of pneumothorax in trauma patients

    OpenAIRE

    Omar, Hesham R; Mangar, Devanand; Khetarpal, Suneel; Shapiro, David H; Kolla, Jaya; Rashad, Rania; Helal, Engy; Camporesi, Enrico M

    2011-01-01

    Abstract Pneumothorax is a common complication following blunt chest wall trauma. In these patients, because of the restrictions regarding immobilization of the cervical spine, Anteroposterior (AP) chest radiograph is usually the most feasible initial study which is not as sensitive as the erect chest X-ray or CT chest for detection of a pneumothorax. We will present 3 case reports which serve for better understanding of the entity of occult pneumothorax. The first case is an example of a tru...

  2. Detection and Classification of Changes in Buildings from Airborne Laser Scanning Data

    Directory of Open Access Journals (Sweden)

    Sudan Xu

    2015-12-01

    Full Text Available The difficulty associated with the Lidar data change detection method is lack of data, which is mainly caused by occlusion or pulse absorption by the surface material, e.g., water. To address this challenge, we present a new strategy for detecting buildings that are “changed”, “unchanged”, or “unknown”, and quantifying the changes. The designation “unknown” is applied to locations where, due to lack of data in at least one of the epochs, it is not possible to reliably detect changes in the structure. The process starts with classified data sets in which buildings are extracted. Next, a point-to-plane surface difference map is generated by merging and comparing the two data sets. Context rules are applied to the difference map to distinguish between “changed”, “unchanged”, and “unknown”. Rules are defined to solve problems caused by the lack of data. Further, points labelled as “changed” are re-classified into changes to roofs, walls, dormers, cars, constructions above the roof line, and undefined objects. Next, all the classified changes are organized as changed building objects, and the geometric indices are calculated from their 3D minimum bounding boxes. Performance analysis showed that 80%–90% of real changes are found, of which approximately 50% are considered relevant.

  3. 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

  4. Elimination Voltammetry with Linear Scan as a New Detection Method for DNA Sensors

    Directory of Open Access Journals (Sweden)

    Rene Kizek

    2005-11-01

    Full Text Available The paper describes successful coupling of adsorptive transfer stripping (AdTS andelimination voltammetry with linear scan (EVLS for the resolution of reduction signals of cytosine (Cand adenine (A residues in hetero-oligodeoxynucleotides (ODNs. Short ODNs (9-mers and 20-merswere adsorbed from a small volume on a hanging mercury drop electrode (HMDE. After washing ofthe ODN-modified electrode by water and its transferring to an electrochemical cell, voltammetric curves were measured. The AdTS EVLS was able to determine of C/A ratio of ODNs through theelimination function conserving the diffusion current component and eliminating kinetic and chargingcurrent components. This function, which provides the elimination signal in a peak-counterpeak form,increased the current sensitivity for A and C resolution, and for the recognition of bases sequences inODN chains. Optimal conditions of elimination experiments such as pH, time of adsorption, and scanrate were found. The combination of EVLS with AdTS procedure can be considered as a newdetection method in a DNA sensor.

  5. Stationary Wavelet Transform and AdaBoost with SVM Based Pathological Brain Detection in MRI Scanning.

    Science.gov (United States)

    Nayak, Deepak Ranjan; Dash, Ratnakar; Majhi, Banshidhar

    2017-01-01

    This paper presents an automatic classification system for segregating pathological brain from normal brains in magnetic resonance imaging scanning. The proposed system employs contrast limited adaptive histogram equalization scheme to enhance the diseased region in brain MR images. Two-dimensional stationary wavelet transform is harnessed to extract features from the preprocessed images. The feature vector is constructed using the energy and entropy values, computed from the level- 2 SWT coefficients. Then, the relevant and uncorrelated features are selected using symmetric uncertainty ranking filter. Subsequently, the selected features are given input to the proposed AdaBoost with support vector machine classifier, where SVM is used as the base classifier of AdaBoost algorithm. To validate the proposed system, three standard MR image datasets, Dataset-66, Dataset-160, and Dataset- 255 have been utilized. The 5 runs of k-fold stratified cross validation results indicate the suggested scheme offers better performance than other existing schemes in terms of accuracy and number of features. The proposed system earns ideal classification over Dataset-66 and Dataset-160; whereas, for Dataset- 255, an accuracy of 99.45% is achieved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Spectral imaging technique for retinal perfusion detection using confocal scanning laser ophthalmoscopy

    Science.gov (United States)

    Rasta, Seyed Hossein; Manivannan, Ayyakkannu; Sharp, Peter F.

    2012-11-01

    To evaluate retinal perfusion in the human eye, a dual-wavelength confocal scanning laser ophthalmoscope (cSLO) was developed that provides spectral imaging of the fundus using a combination of red (670 nm) and near-infrared (810 nm) wavelengths. The image of the ocular fundus was analyzed to find out if quantitative measurements of the reflectivity of tissue permit assessment of the oxygen perfusion of tissue. We explored problems that affect the reproducibility of patient measurements such as non-uniformity errors on the image. For the first time, an image processing technique was designed and used to minimize the errors of oxygen saturation measurements by illumination correction in retina wide field by increasing SNR. Retinal images were taken from healthy and diabetic retinopathy eyes using the cSLO with a confocal aperture of 100 μm. The ratio image (RI) of red/IR, as oxygen saturation (SO2) index, was calculated for normal eyes. The image correction technique improved the reproducibility of the measurements. Average RI intensity variation of healthy retina tissue was determined within a range of about 5.5%. The capability of the new technique to discriminate oxygenation levels of retinal artery and vein was successfully demonstrated and showed good promise in the diagnosis of the perfused retina.

  7. A portable scanning lidar for real-time detection of fugitive dust emissions from multisource facilities

    Energy Technology Data Exchange (ETDEWEB)

    Emmitt, G.D. [Simpson Weather Associates, Inc., Charlottesville, VA (United States)

    1994-12-31

    A 400 mj, incoherent, pulsed, scanning CO{sub 2} lidar referred to as the Portable Laser for Coal Emission Mapping (PLACEM) is combined with a real-time version of EPA`s Industrial Source Complex - Short Term (ISCST) model to map TSP concentrations and dry deposition of fugitive particulate emissions from multiple sources within a coal handling complex. A Simpson Weather Associates concept, funded by Pier IX (a subsidiary of Zeigler Coal Handling Company), PLACEM was developed in response to the need for an eye-safe laser technique for (1) assessing the relative contribution of intermittent dust generating activities and sources within a coal transshipment facility, (2) evaluating the efficiency of various dust control measures, and (3) developing a means to assess compliance with pending Clean Air Act (CAA, 1990) regulations requiring Continuous Emission Monitoring (CEM). Integration of the PLACEM observations with the ISCST2 provides a means of dynamically calibrating the model for use with conventional in situ particulate monitors. Both simulated and real observations are presented to demonstrate the viability and utility of this lidar/model approach to fugitive emission monitoring.

  8. 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.

  9. Computer-aided detection system for lung cancer in computed tomography scans: Review and future prospects

    Science.gov (United States)

    2014-01-01

    Introduction The goal of this paper is to present a critical review of major Computer-Aided Detection systems (CADe) for lung cancer in order to identify challenges for future research. CADe systems must meet the following requirements: improve the performance of radiologists providing high sensitivity in the diagnosis, a low number of false positives (FP), have high processing speed, present high level of automation, low cost (of implementation, training, support and maintenance), the ability to detect different types and shapes of nodules, and software security assurance. Methods The relevant literature related to “CADe for lung cancer” was obtained from PubMed, IEEEXplore and Science Direct database. Articles published from 2009 to 2013, and some articles previously published, were used. A systemic analysis was made on these articles and the results were summarized. Discussion Based on literature search, it was observed that many if not all systems described in this survey have the potential to be important in clinical practice. However, no significant improvement was observed in sensitivity, number of false positives, level of automation and ability to detect different types and shapes of nodules in the studied period. Challenges were presented for future research. Conclusions Further research is needed to improve existing systems and propose new solutions. For this, we believe that collaborative efforts through the creation of open source software communities are necessary to develop a CADe system with all the requirements mentioned and with a short development cycle. In addition, future CADe systems should improve the level of automation, through integration with picture archiving and communication systems (PACS) and the electronic record of the patient, decrease the number of false positives, measure the evolution of tumors, evaluate the evolution of the oncological treatment, and its possible prognosis. PMID:24713067

  10. 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

    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 mic...... for QTL segregating on Bos taurus chromosome (BTA)1, BTA7, BTA10, and BTA26. On each of these chromosomes, several QTL were detected affecting more than one of the fertility traits investigated in this study. Evidence for segregation of additional QTL on BTA2, BTA9, and BTA24 was found...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  12. Detection of secondary phases in duplex stainless steel by magnetic force microscopy and scanning Kelvin probe force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ramírez-Salgado, J. [Instituto Mexicano del Petróleo, Dirección de Investigación y Posgrado, Eje Central Norte Lázaro Cárdenas, No. 152, 07730 D.F., México (Mexico); Domínguez-Aguilar, M.A., E-mail: madoming@imp.mx [Instituto Mexicano del Petróleo, Dirección de Investigación y Posgrado, Eje Central Norte Lázaro Cárdenas, No. 152, 07730 D.F., México (Mexico); Castro-Domínguez, B. [University of Tokyo, Department of Chemical System Engineering, Faculty of Engineering Bldg. 5, 7F 722, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8656 (Japan); Hernández-Hernández, P. [Instituto Mexicano del Petróleo, Dirección de Investigación y Posgrado, Eje Central Norte Lázaro Cárdenas, No. 152, 07730 D.F., México (Mexico); Newman, R.C. [University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College Street, Toronto M5S 3E5 (Canada)

    2013-12-15

    The secondary phase transformations in a commercial super duplex stainless steel were investigated by micro-chemical analyses and high resolution scanning probe microscopy. Energy dispersive X-ray and electron probe detected ferrite and austenite as well as secondary phases in unetched aged duplex stainless steel type 25Cr-7Ni-3Mo. Volta potential indicated that nitride and sigma appeared more active than ferrite, while secondary austenite and austenite presented a nobler potential. Reversal order in nobility is thought to be attributable to the potential ranking provided by oxide nature diversity as a result of secondary phase surface compositions on steel. After eutectoid transformation, secondary austenite was detected by electron probe microanalysis, whereas atomic force microscopy distinguished this phase from former austenite by image contrast. Magnetic force microscopy revealed a “ghosted” effect on the latter microstructure probably derived from metal memory reminiscence of mechanical polishing at passivity and long range magnetic forces of ferrite phase. - Highlights: • Nobility detection of secondary phases by SKPFM in DSS particles is not a straightforward procedure. • As Volta potential and contrast are not always consistent SKPFM surface oxides is thought played an important role in detection. • AFM distinguished secondary austenite from former austenite by image contrast though SEM required EPMA.

  13. H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers.

    Science.gov (United States)

    Przybojewska, B; Jagiello, A; Jalmuzna, P

    2000-08-01

    Bladder cancer is one of the leading causes of cancer death in most developed countries. In this work, 19 bladder cancer specimens, along with their infiltrations of the urinary bladder wall from the same patients, were examined for the presence of H-RAS, K-RAS, and N-RAS activation using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The H-RAS activation was found in 15 (about 84%) of the 19 bladder cancers studied. The same results were obtained in the infiltrating urinary bladder wall samples. N-RAS gene mutations were observed in all cases (except 1) in which H-RAS gene mutations were detected. The results suggest a strong relationship between H-RAS and N-RAS gene activation in bladder cancer. Changes in the K-RAS gene in bladder cancers seem to be a rare event; this is in agreement with findings of other authors. We found activation of the gene in one specimen of bladder cancer and its infiltration of the urinary bladder wall in the same patient.

  14. Long-Term Survival with Regorafenib in KRAS-Mutated Metastatic Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Marie-Laure Amram

    2017-11-01

    Full Text Available Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer progressing on standard therapies. Here, we describe the clinical history of a 63-year-old male patient who was treated with regorafenib in the pivotal CORRECT trial. The patient was initially diagnosed in November 2008 with nonmetastatic KRAS-mutated (exon 2, codon 12 rectal cancer. He underwent successful surgery and was treated with 5 cycles of adjuvant chemotherapy. In 2010, lung metastases (KRAS-mutated were detected and the patient received 6 cycles of FOLFIRI plus bevacizumab. By January 2011, the metastases had progressed. The patient, who was asymptomatic with an Eastern Cooperative Oncology Group performance status of 0, was enrolled onto the CORRECT trial and received best supportive care plus regorafenib (160 mg once daily for 3 weeks of a 4-week cycle over a period of 2 years, during which time the disease remained stable and the patient remained asymptomatic. Grade 1 anemia and thrombocytopenia were the only treatment-emergent adverse events reported. After receiving 26 cycles of regorafenib, a majority of the lung lesions progressed, and third-line palliative 5-fluorouracil, leucovorin, and oxaliplatin chemotherapy was administered. The patient died in May 2016.

  15. KRAS polymorphisms are associated with survival of CRC in Chinese population.

    Science.gov (United States)

    Dai, Qiong; Wei, Hui Lian; Huang, Juan; Zhou, Tie Jun; Chai, Li; Yang, Zhi-Hui

    2016-04-01

    rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

  16. Specific and Efficient Regression of Cancers Harboring KRAS Mutation by Targeted RNA Replacement.

    Science.gov (United States)

    Kim, Sung Jin; Kim, Ju Hyun; Yang, Bitna; Jeong, Jin-Sook; Lee, Seong-Wook

    2017-02-01

    Mutations in the KRAS gene, which persistently activate RAS function, are most frequently found in many types of human cancers. Here, we proposed and verified a new approach against cancers harboring the KRAS mutation with high cancer selectivity and efficient anti-cancer effects based on targeted RNA replacement. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically target and reprogram the mutant KRAS G12V transcript to induce therapeutic gene activity in cells. Adenoviral vectors containing the specific ribozymes with downstream suicide gene were constructed and then infection with the adenoviruses specifically downregulated KRAS G12V expression and killed KRAS G12V-harboring cancer cells additively upon pro-drug treatment, but it did not affect the growth of wild-type KRAS-expressing cells. Minimal liver toxicity was noted when the adenoviruses were administered systemically in vivo. Importantly, intratumoral injection of the adenoviruses with pro-drug treatment specifically and significantly impeded the growth of xenografted tumors harboring KRAS G12V through a trans-splicing reaction with the target RNA. In contrast, xenografted tumors harboring wild-type KRAS were not affected by the adenoviruses. Therefore, RNA replacement with a mutant KRAS-targeting trans-splicing ribozyme is a potentially useful therapeutic strategy to combat tumors harboring KRAS mutation. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  17. STK33 kinase activity is nonessential in KRAS-dependent cancer cells.

    Science.gov (United States)

    Babij, Carol; Zhang, Yihong; Kurzeja, Robert J; Munzli, Anke; Shehabeldin, Amro; Fernando, Manory; Quon, Kim; Kassner, Paul D; Ruefli-Brasse, Astrid A; Watson, Vivienne J; Fajardo, Flordeliza; Jackson, Angela; Zondlo, James; Sun, Yu; Ellison, Aaron R; Plewa, Cherylene A; San, Miguel Tisha; Robinson, John; McCarter, John; Schwandner, Ralf; Judd, Ted; Carnahan, Josette; Dussault, Isabelle

    2011-09-01

    Despite the prevalence of KRAS mutations in human cancers, there remain no targeted therapies for treatment. The serine-threonine kinase STK33 has been proposed to be required for the survival of mutant KRAS-dependent cell lines, suggesting that small molecule kinase inhibitors of STK33 may be useful to treat KRAS-dependent tumors. In this study, we investigated the role of STK33 in mutant KRAS human cancer cells using RNA interference, dominant mutant overexpression, and small molecule inhibitors. As expected, KRAS downregulation decreased the survival of KRAS-dependent cells. In contrast, STK33 downregulation or dominant mutant overexpression had no effect on KRAS signaling or survival of these cells. Similarly, a synthetic lethal siRNA screen conducted in a broad panel of KRAS wild-type or mutant cells identified KRAS but not STK33 as essential for survival. We also obtained similar negative results using small molecule inhibitors of the STK33 kinase identified by high-throughput screening. Taken together, our findings refute earlier proposals that STK33 inhibition may be a useful therapeutic approach to target human KRAS mutant tumors. ©2011 AACR.

  18. 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

  19. 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.

  20. Rare Case of Intratracheal Metastasis Detected on 68Ga-Prostate-Specific Membrane Antigen PET/CT Scan in a Case of Thyroglobulin Elevated Negative Iodine Scan Syndrome.

    Science.gov (United States)

    Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Oommen, Karuna Elza; Jayakumar, R

    2018-04-01

    A 64-year-old woman underwent completion thyroidectomy with upper tracheal ring resection and right-sided neck dissection for papillary carcinoma of the thyroid infiltrating the trachea and was given I radioiodine treatment. Three years later, she presented with hemoptysis. On evaluation, she had increased serum thyroglobulin and negative iodine scan (TENIS). F-FDG PET/CT scan did not identify any site of disease. One year later, Ga-PSMA scan done revealed a moderate focal tracer-avid intratracheal soft tissue; biopsy revealed it to be metastatic papillary carcinoma of the thyroid. This case kindles the possibility of using Ga-PSMA PET/CT to reveal occult disease in cases of TENIS.

  1. Radionuclide scanning

    International Nuclear Information System (INIS)

    Shapiro, B.

    1986-01-01

    Radionuclide scanning is the production of images of normal and diseased tissues and organs by means of the gamma-ray emissions from radiopharmaceutical agents having specific distributions in the body. The gamma rays are detected at the body surface by a variety of instruments that convert the invisible rays into visible patterns representing the distribution of the radionuclide in the body. The patterns, or images, obtained can be interpreted to provide or to aid diagnoses, to follow the course of disease, and to monitor the management of various illnesses. Scanning is a sensitive technique, but its specificity may be low when interpreted alone. To be used most successfully, radionuclide scanning must be interpreted in conjunction with other techniques, such as bone radiographs with bone scans, chest radiographs with lung scans, and ultrasonic studies with thyroid scans. Interpretation is also enhanced by providing pertinent clinical information because the distribution of radiopharmaceutical agents can be altered by drugs and by various procedures besides physiologic and pathologic conditions. Discussion of the patient with the radionuclide scanning specialist prior to the study and review of the results with that specialist after the study are beneficial

  2. Picometer stable scan mechanism for gravitational wave detection in space: LISA PAAM

    Science.gov (United States)

    Pijnenburg, J. A. C. M.; Rijnveld, N.

    2017-11-01

    Detection and observation of gravitational waves requires extreme stability in the frequency range 0.03 mHz to 1 Hz. The Laser Interferometer Space Antenna (LISA) mission will attain this by creating a giant interferometer in space, based on free floating proof masses in three spacecrafts. Due to orbit evolution and time delay in the interferometer arms, the direction of transmitted light changes. To solve this problem, a picometer stable Point-Ahead Angle Mechanism (PAAM) was designed, realized and successfully tested. The PAAM concept is based on a rotatable mirror. The critical requirements are the contribution to the optical path length (less than 1.4 pm / rt Hz) and the angular jitter (less than 8 nrad / rt Hz). Extreme dimensional stability is achieved by manufacturing a monolithical Haberland hinge mechanism out of Ti6Al4V, through high precision wire erosion. Extreme thermal stability is realized by placing the thermal center on the surface of the mirror. Because of piezo actuator noise and leakage, the PAAM has to be controlled in closed-loop. To meet the requirements in the low frequencies, an active target capacitance-to-digital converter is used. Interferometric measurements with a triangular resonant cavity in vacuum proved that the PAAM meets the requirements.

  3. Computer-aided detection (CAD) of lung nodules in CT scans: radiologist performance and reading time with incremental CAD assistance

    International Nuclear Information System (INIS)

    Roos, Justus E.; Paik, David; Olsen, David; Liu, Emily G.; Leung, Ann N.; Mindelzun, Robert; Choudhury, Kingshuk R.; Napel, Sandy; Rubin, Geoffrey D.; Chow, Lawrence C.; Naidich, David P.

    2010-01-01

    The diagnostic performance of radiologists using incremental CAD assistance for lung nodule detection on CT and their temporal variation in performance during CAD evaluation was assessed. CAD was applied to 20 chest multidetector-row computed tomography (MDCT) scans containing 190 non-calcified ≥3-mm nodules. After free search, three radiologists independently evaluated a maximum of up to 50 CAD detections/patient. Multiple free-response ROC curves were generated for free search and successive CAD evaluation, by incrementally adding CAD detections one at a time to the radiologists' performance. The sensitivity for free search was 53% (range, 44%-59%) at 1.15 false positives (FP)/patient and increased with CAD to 69% (range, 59-82%) at 1.45 FP/patient. CAD evaluation initially resulted in a sharp rise in sensitivity of 14% with a minimal increase in FP over a time period of 100 s, followed by flattening of the sensitivity increase to only 2%. This transition resulted from a greater prevalence of true positive (TP) versus FP detections at early CAD evaluation and not by a temporal change in readers' performance. The time spent for TP (9.5 s ± 4.5 s) and false negative (FN) (8.4 s ± 6.7 s) detections was similar; FP decisions took two- to three-times longer (14.4 s ± 8.7 s) than true negative (TN) decisions (4.7 s ± 1.3 s). When CAD output is ordered by CAD score, an initial period of rapid performance improvement slows significantly over time because of non-uniformity in the distribution of TP CAD output and not to a changing reader performance over time. (orig.)

  4. 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.

  5. STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability.

    Science.gov (United States)

    Luo, Tuoping; Masson, Kristina; Jaffe, Jacob D; Silkworth, Whitney; Ross, Nathan T; Scherer, Christina A; Scholl, Claudia; Fröhling, Stefan; Carr, Steven A; Stern, Andrew M; Schreiber, Stuart L; Golub, Todd R

    2012-02-21

    Approximately 30% of human cancers harbor oncogenic gain-of-function mutations in KRAS. Despite interest in KRAS as a therapeutic target, direct blockade of KRAS function with small molecules has yet to be demonstrated. Based on experiments that lower mRNA levels of protein kinases, KRAS-dependent cancer cells were proposed to have a unique requirement for the serine/threonine kinase STK33. Thus, it was suggested that small-molecule inhibitors of STK33 might have therapeutic benefit in these cancers. Here, we describe the development of selective, low nanomolar inhibitors of STK33's kinase activity. The most potent and selective of these, BRD8899, failed to kill KRAS-dependent cells. While several explanations for this result exist, our data are most consistent with the view that inhibition of STK33's kinase activity does not represent a promising anti-KRAS therapeutic strategy.

  6. Using rapid scan EPR to improve the detection limit of quantitative EPR by more than one order of magnitude

    OpenAIRE

    Möser, J.; Lips, K.; Tseytlin, M.; Eaton, G.; Eaton, S.; Schnegg, A

    2017-01-01

    X band rapid scan EPR was implemented on a commercially available Bruker ELEXSYS E580 spectrometer. Room temperature rapid scan and continuous wave EPR spectra were recorded for amorphous silicon powder samples. By comparing the resulting signal intensities the feasibility of performing quantitative rapid scan EPR is demonstrated. For different hydrogenated amorphous silicon samples, rapid scan EPR results in signal to noise improvements by factors between 10 and 50. Rapid scan EPR is thus ca...

  7. A Voice-Detecting Sensor and a Scanning Keyboard Emulator to Support Word Writing by Two Boys with Extensive Motor Disabilities

    Science.gov (United States)

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Green, Vanessa; Chiapparino, Claudia; Stasolla, Fabrizio; Oliva, Doretta

    2009-01-01

    The present study assessed the use of a voice-detecting sensor interfaced with a scanning keyboard emulator to allow two boys with extensive motor disabilities to write. Specifically, the study (a) compared the effects of the voice-detecting sensor with those of a familiar pressure sensor on the boys' writing time, (b) checked which of the sensors…

  8. Myocardial KRAS(G12D) expression does not cause cardiomyopathy in mice.

    Science.gov (United States)

    Dalin, Martin G; Zou, Zhiyuan; Scharin-Täng, Margareta; Safari, Roghaiyeh; Karlsson, Christin; Bergo, Martin O

    2014-02-01

    Germ-line mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway cause developmental disorders called RASopathies. Hypertrophic cardiomyopathy (HCM) is the most common myocardial pathology and a leading cause of death in RASopathy patients. KRAS mutations are found in Noonan and cardio-facio-cutaneous syndromes. KRAS mutations, unlike mutations of RAF1 and HRAS, are rarely associated with HCM. This has been attributed to the fact that germ-line KRAS mutations cause only a moderate up-regulation of the MAPK pathway. Highly bioactive KRAS mutations have been hypothesized to cause severe cardiomyopathy incompatible with life. The aim of this study was to define the impact of KRAS(G12D) expression in the heart. To generate mice with endogenous cardiomyocyte-specific KRAS(G12D) expression (cKRAS(G12D) mice), we bred mice with a Cre-inducible allele expressing KRAS(G12D) from its endogenous promoter (Kras2(LSL)) to mice expressing Cre under control of the cardiomyocyte-specific α-myosin heavy chain promoter (αMHC-Cre). cKRAS(G12D) mice showed high levels of myocardial ERK and AKT signalling. However, surprisingly, cKRAS(G12D) mice were born in Mendelian ratios, appeared healthy, and had normal function, size, and histology of the heart. Mice with cardiomyocyte-specific KRAS(G12D) expression do not develop heart pathology. These results challenge the view that the level of MAPK activation correlates with the severity of HCM in RASopathies and suggests that MAPK-independent strategies may be of interest in the development of new treatments for these syndromes.

  9. Oncogenic K-Ras Activates p38 to Maintain Colorectal Cancer Cell Proliferation during MEK Inhibition

    Directory of Open Access Journals (Sweden)

    Winan J. van Houdt

    2010-01-01

    Full Text Available Background: Colon carcinomas frequently contain activating mutations in the K-ras proto-oncogene. K-ras itself is a poor drug target and drug development efforts have mostly focused on components of the classical Ras-activated MEK/ERK pathway. Here we have studied whether endogenous oncogenic K-ras affects the dependency of colorectal tumor cells on MEK/ERK signaling.

  10. A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

    OpenAIRE

    Grace R. Anderson; Peter S. Winter; Kevin H. Lin; Daniel P. Nussbaum; Merve Cakir; Elizabeth M. Stein; Ryan S. Soderquist; Lorin Crawford; Jim C. Leeds; Rachel Newcomb; Priya Stepp; Catherine Yip; Suzanne E. Wardell; Jennifer P. Tingley; Moiez Ali

    2017-01-01

    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 tiss...

  11. Optimization of input parameters of supra-threshold stochastic resonance image processing algorithm for the detection of abdomino-pelvic tumors on PET/CT scan

    International Nuclear Information System (INIS)

    Pandey, Anil Kumar; Saroha, Kartik; Patel, C.D.; Bal, C.S.; Kumar, Rakesh

    2016-01-01

    Administration of diuretics increases the urine output to clear radioactive urine from kidneys and bladder. Hence post-diuretic pelvic PET/CT scan enhances the probability of detection of abdomino-pelvic tumor. However, it causes discomfort in patients and has some side effects also. Application of supra threshold stochastic resonance (SSR) image processing algorithm on Pre-diuretic PET/CT scan may also increase the probability of detection of these tumors. Amount of noise and threshold are two variable parameters that effect the final image quality. This study was conducted to investigate the effect of these two variable parameters on the detection of abdomen-pelvic tumor

  12. Detection of Azo Dyes in Curry Powder Using a 1064-nm Dispersive Point-Scan Raman System

    Directory of Open Access Journals (Sweden)

    Sagar Dhakal

    2018-04-01

    Full Text Available Curry powder is extensively used in Southeast Asian dishes. It has been subject to adulteration by azo dyes. This study used a newly developed 1064 nm dispersive point-scan Raman system for detection of metanil yellow and Sudan-I contamination in curry powder. Curry powder was mixed with metanil yellow and (separately with Sudan-I, at concentration levels of 1%, 3%, 5%, 7%, and 10% (w/w. Each sample was packed into a nickel-plated sample container (25 mm × 25 mm × 1 mm. One Raman spectral image of each sample was acquired across the 25 mm × 25 mm surface area. Intensity threshold value was applied to the spectral images of Sudan-I mixtures (at 1593 cm−1 and metanil yellow mixtures (at 1147 cm−1 to obtain binary detection images. The results show that the number of detected adulterant pixels is linearly correlated with the sample concentration (R2 = 0.99. The Raman system was further used to obtain a Raman spectral image of a curry powder sample mixed together with Sudan-I and metanil yellow, with each contaminant at equal concentration of 5% (w/w. The multi-component spectra of the mixture sample were decomposed using self-modeling mixture analysis (SMA to extract pure component spectra, which were then identified as matching those of Sudan-I and metanil yellow using spectral information divergence (SID values. The results show that the 1064 nm dispersive Raman system is a potential tool for rapid and nondestructive detection of multiple chemical contaminants in the complex food matrix.

  13. Inhibition of prenylated KRAS in a lipid environment.

    Directory of Open Access Journals (Sweden)

    Johanna M Jansen

    Full Text Available RAS mutations lead to a constitutively active oncogenic protein that signals through multiple effector pathways. In this chemical biology study, we describe a novel coupled biochemical assay that measures activation of the effector BRAF by prenylated KRASG12V in a lipid-dependent manner. Using this assay, we discovered compounds that block biochemical and cellular functions of KRASG12V with low single-digit micromolar potency. We characterized the structural basis for inhibition using NMR methods and showed that the compounds stabilized the inactive conformation of KRASG12V. Determination of the biophysical affinity of binding using biolayer interferometry demonstrated that the potency of inhibition matches the affinity of binding only when KRAS is in its native state, namely post-translationally modified and in a lipid environment. The assays we describe here provide a first-time alignment across biochemical, biophysical, and cellular KRAS assays through incorporation of key physiological factors regulating RAS biology, namely a negatively charged lipid environment and prenylation, into the in vitro assays. These assays and the ligands we discovered are valuable tools for further study of KRAS inhibition and drug discovery.

  14. KRAS mutation: should we test for it, and does it matter?

    Science.gov (United States)

    Roberts, Patrick J; Stinchcombe, Thomas E

    2013-03-10

    Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Previously, lung cancer was simplistically divided into non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, in the last decade, we have gone from a simplistic binary system of classifying lung cancer to defining NSCLC on the basis of molecular subsets. KRAS mutations represent the most common molecular change in NSCLC. The presence of KRAS mutation has been shown to be associated with a poor prognosis in NSCLC, but this is of little clinical utility. More important is determining the clinical utility of KRAS mutational analysis for predicting benefit of chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, or other novel therapeutics. Current data does not support the routine use of KRAS mutational analysis for predicting chemotherapy benefit. Additionally, there was significant interest in using KRAS status to select patients for EGFR TKI and anti-EGFR monoclonal antibodies. However, the EGFR mutational status has demonstrated significant predictive value in the selection of patients for EGFR TKI therapy and is now the preferred test. An association between KRAS mutational status and benefit of anti-EGFR monoclonal antibodies has not been demonstrated in NSCLC. Here we review, in the context of NSCLC, the underlying biology of KRAS mutations, the predictive value of KRAS mutations for therapeutic intervention, and the integration of KRAS mutational testing into our current clinical paradigms.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Dual channel detection of ultra low concentration of bacteria in real time by scanning fluorescence correlation spectroscopy

    Science.gov (United States)

    Altamore, Ilaria; Lanzano, Luca; Gratton, Enrico

    2013-06-01

    We describe a novel method to detect very low concentrations of bacteria in water. Our device consists of a portable horizontal geometry small confocal microscope with large pinhole and a holder for cylindrical cuvettes containing the sample. Two motors provide fast rotational and slow vertical motion of the cuvette so the device looks like a simplified flow cytometer without flow. To achieve high sensitivity, the design has two detection channels. Bacteria are stained by two different nucleic acid dyes and excited with two different lasers. Data are analyzed with a correlation filter based on particle passage pattern recognition. The passage of a particle through the illumination volume is compared with a Gaussian pattern in both channels. The width of the Gaussian correlates with the time of passage of the particle so one particle is counted when the algorithm finds a match with a Gaussian in both channels. The concentration of particles in the sample is deduced from the total number of coincident hits and the total volume scanned. This portable setup provides higher sensitivity, low-cost advantage, and it can have a wide use ranging from clinical applications to pollution monitors and water and air quality control.

  20. Dual channel detection of ultra low concentration of bacteria in real time by scanning fluorescence correlation spectroscopy

    International Nuclear Information System (INIS)

    Altamore, Ilaria; Lanzano, Luca; Gratton, Enrico

    2013-01-01

    We describe a novel method to detect very low concentrations of bacteria in water. Our device consists of a portable horizontal geometry small confocal microscope with large pinhole and a holder for cylindrical cuvettes containing the sample. Two motors provide fast rotational and slow vertical motion of the cuvette so the device looks like a simplified flow cytometer without flow. To achieve high sensitivity, the design has two detection channels. Bacteria are stained by two different nucleic acid dyes and excited with two different lasers. Data are analyzed with a correlation filter based on particle passage pattern recognition. The passage of a particle through the illumination volume is compared with a Gaussian pattern in both channels. The width of the Gaussian correlates with the time of passage of the particle so one particle is counted when the algorithm finds a match with a Gaussian in both channels. The concentration of particles in the sample is deduced from the total number of coincident hits and the total volume scanned. This portable setup provides higher sensitivity, low-cost advantage, and it can have a wide use ranging from clinical applications to pollution monitors and water and air quality control. (paper)

  1. Surveying Drifting Icebergs and Ice Islands: Deterioration Detection and Mass Estimation with Aerial Photogrammetry and Laser Scanning

    Directory of Open Access Journals (Sweden)

    Anna J. Crawford

    2018-04-01

    Full Text Available Icebergs and ice islands (large, tabular icebergs are challenging targets to survey due to their size, mobility, remote locations, and potentially difficult environmental conditions. Here, we assess the precision and utility of aerial photography surveying with structure-from-motion multi-view stereo photogrammetry processing (SfM and vessel-based terrestrial laser scanning (TLS for iceberg deterioration detection and mass estimation. For both techniques, we determine the minimum amount of change required to reliably resolve iceberg deterioration, the deterioration detection threshold (DDT, using triplicate surveys of two iceberg survey targets. We also calculate their relative uncertainties for iceberg mass estimation. The quality of deployed Global Positioning System (GPS units that were used for drift correction and scale assignment was a major determinant of point cloud precision. When dual-frequency GPS receivers were deployed, DDT values of 2.5 and 0.40 m were calculated for the TLS and SfM point clouds, respectively. In contrast, values of 6.6 and 3.4 m were calculated when tracking beacons with lower-quality GPS were used. The SfM dataset was also more precise when used for iceberg mass estimation, and we recommend further development of this technique for iceberg-related end-uses.

  2. A new method to detect and correct sample tilt in scanning transmission electron microscopy bright-field imaging

    Energy Technology Data Exchange (ETDEWEB)

    Brown, H.G. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Ishikawa, R.; Sánchez-Santolino, G. [Institute of Engineering Innovation, School of Engineering, University of Tokyo, Tokyo 113-8656 (Japan); Lugg, N.R., E-mail: shibata@sigma.t.u-tokyo.ac.jp [Institute of Engineering Innovation, School of Engineering, University of Tokyo, Tokyo 113-8656 (Japan); Ikuhara, Y. [Institute of Engineering Innovation, School of Engineering, University of Tokyo, Tokyo 113-8656 (Japan); Allen, L.J. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Shibata, N. [Institute of Engineering Innovation, School of Engineering, University of Tokyo, Tokyo 113-8656 (Japan)

    2017-02-15

    Important properties of functional materials, such as ferroelectric shifts and octahedral distortions, are associated with displacements of the positions of lighter atoms in the unit cell. Annular bright-field scanning transmission electron microscopy is a good experimental method for investigating such phenomena due to its ability to image light and heavy atoms simultaneously. To map atomic positions at the required accuracy precise angular alignment of the sample with the microscope optical axis is necessary, since misalignment (tilt) of the specimen contributes to errors in position measurements of lighter elements in annular bright-field imaging. In this paper it is shown that it is possible to detect tilt with the aid of images recorded using a central bright-field detector placed within the inner radius of the annular bright-field detector. For a probe focus near the middle of the specimen the central bright-field image becomes especially sensitive to tilt and we demonstrate experimentally that misalignment can be detected with a precision of less than a milliradian, as we also confirm in simulation. Coma in the probe, an aberration that can be misidentified as tilt of the specimen, is also investigated and it is shown how the effects of coma and tilt can be differentiated. The effects of tilt may be offset to a large extent by shifting the diffraction plane detector an amount equivalent to the specimen tilt and we provide an experimental proof of principle of this using a segmented detector system. - Highlights: • Octahedral distortions are associated with displacements of lighter atoms. • Annular bright-field imaging is sensitive to light and heavy atoms simultaneously. • Mistilt of the specimen leads to errors in position measurements of lighter elements. • It is possible to detect tilt using images taken by a central bright-field detector. • Tilt may be offset by shifting the diffraction plane detector by an equivalent amount.

  3. 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

  4. KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Erben, Philipp, E-mail: philipp.erben@medma.uni-heidelberg.de [III. Medizinische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Stroebel, Philipp [Pathologisches Institut, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Horisberger, Karoline [Chirurgische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Popa, Juliana; Bohn, Beatrice; Hanfstein, Benjamin [III. Medizinische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Kaehler, Georg; Kienle, Peter; Post, Stefan [Chirurgische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Wenz, Frederik [Klinik fuer Strahlentherapie und Radioonkologie, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Hochhaus, Andreas [III. Medizinische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany); Klinik fuer Innere Medizin II, Abteilung Haematologie/Onkologie, Universitaetsklinikum Jena, Jena (Germany); Hofheinz, Ralf-Dieter [III. Medizinische Klinik, Universitaetsmedizin Mannheim, Universitaet Heidelberg, Mannheim (Germany)

    2011-11-15

    Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

  5. KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Erben, Philipp; Ströbel, Philipp; Horisberger, Karoline; Popa, Juliana; Bohn, Beatrice; Hanfstein, Benjamin; Kähler, Georg; Kienle, Peter; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas; Hofheinz, Ralf-Dieter

    2011-01-01

    Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan–Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

  6. 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.

  7. Detection and characterization of Budd-Chiari syndrome with inferior vena cava obstruction: Comparison of fixed and flexible delayed scan time of computed tomography venography.

    Science.gov (United States)

    Zhou, Peng-Li; Wu, Gang; Han, Xin-Wei; Bi, Yong-Hua; Zhang, Wen-Guang; Wu, Zheng-Yang

    2017-06-01

    To compare the results of computed tomography venography (CTV) with a fixed and a flexible delayed scan time for Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction. A total of 209 consecutive BCS patients with IVC obstruction underwent either a CTV with a fixed delayed scan time of 180s (n=87) or a flexible delayed scan time for good image quality according to IVC blood flow in color Doppler ultrasonography (n=122). The IVC blood flow velocity was measured using a color Doppler ultrasound prior to CT scan. Image quality was classified as either good, moderate, or poor. Image quality, surrounding structures and the morphology of the IVC obstruction were compared between the two groups using a χ 2 -test or paired or unpaired t-tests as appropriate. Inter-observer agreement was assessed using Kappa statistics. There was no significant difference in IVC blood flow velocity between the two groups. Overall image quality, surrounding structures and IVC obstruction morphology delineation on the flexible delayed scan time of CTV images were rated better relative to those obtained by fixed delayed scan time of CTV images (ptime of CTV. There were no significant differences in Kappa statistics between Group A and Group B. The flexible delayed scan time of CTV was associated with better detection and more reliable characterization of BCS with IVC obstruction compared to a fixed delayed scan time. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 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.

  9. 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%.

  10. Three-dimensional imaging of individual point defects using selective detection angles in annular dark field scanning transmission electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jared M.; Im, Soohyun; Windl, Wolfgang; Hwang, Jinwoo, E-mail: hwang.458@osu.edu

    2017-01-15

    We propose a new scanning transmission electron microscopy (STEM) technique that can realize the three-dimensional (3D) characterization of vacancies, lighter and heavier dopants with high precision. Using multislice STEM imaging and diffraction simulations of β-Ga{sub 2}O{sub 3} and SrTiO{sub 3}, we show that selecting a small range of low scattering angles can make the contrast of the defect-containing atomic columns substantially more depth-dependent. The origin of the depth-dependence is the de-channeling of electrons due to the existence of a point defect in the atomic column, which creates extra “ripples” at low scattering angles. The highest contrast of the point defect can be achieved when the de-channeling signal is captured using the 20–40 mrad detection angle range. The effect of sample thickness, crystal orientation, local strain, probe convergence angle, and experimental uncertainty to the depth-dependent contrast of the point defect will also be discussed. The proposed technique therefore opens new possibilities for highly precise 3D structural characterization of individual point defects in functional materials. - Highlights: • A new electron microscopy technique that can visualize 3D position of point defect is proposed. • The technique relies on the electron de-channeling signals at low scattering angles. • The technique enables precise determination of the depth of vacancies and lighter impurity atoms.

  11. Far-ultraviolet imaging spectrograph and scanning grating spectrometers for the Remote Atmospheric and Ionospheric Detection System

    International Nuclear Information System (INIS)

    McCoy, R.P.; Meier, R.R.; Wolfram, K.D.; Picone, J.M.; Thonnard, S.E.; Fritz, G.G.; Morrill, J.S.; Christensen, A.B.; Kayser, D.C.; Pranke, J.B.; Straus, P.R.

    1994-01-01

    The Remote Atmospheric and Ionospheric Detection System (RAIDS) experiment is an optical remote sensing platform consisting of eight sensors, (spectrographs, spectrometers, and photometers) covering the wavelength range 550 to 8744 angstrom. RAIDS employs a mechanical scan platform to view the Earth's limb and measure line-of-sight column emission from tangent altitudes from 50 to 750 km. These measurements provide vertical profiles of atmospheric dayglow and nightglow from the mesosphere to the upper regions of the F-region ionosphere. RAIDS will be flown on the National Oceanographic and Atmospheric Administration (NOAA) J weather satellite through the auspices of the US Air Force Space Test Program. The RAIDS wavelength and altitude coverage allows remote sensing of the major and many minor constituents in the thermosphere and ionosphere. These measurements will be used as part of a proof of concept for remote sensing of ionospheric and neutral density profiles. The RAIDS database will be used to study composition, thermal structure, and couplings between the mesosphere, thermosphere, thermal structure, and couplings between the mesosphere, thermosphere, and ionosphere. RAIDS is a joint venture of the Naval Research Laboratory (NRL) and the Aerospace Corporation. The authors describe the subset of RAIDS instruments developed at NRL covering the far to near UV regions (1,300 to 4,000 angstrom)

  12. 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.

  13. 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

  14. 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

  15. Dosimetric implications of shifts in linear accelerator electron beam energy detected in routine constancy checks: a scanning film densitometry detection method

    International Nuclear Information System (INIS)

    Cross, P.; Wang, Y.

    1993-01-01

    The effects of change in electron beam energy are primarily manifest by changes in the range parameters of the depth ionisation/dose curve. Even for a change of up to 10% in the mean energy at the surface, E O , the dose to the depth of maximum on the central axis changes by less than 1%. Using as a limit of acceptability that the change in the therapeutic range (R 85 ) should not be more than ±1.5 mm, the precision required by beam energy checking is that a change of 0.4 MeV in E O should be detectable for all electron beams provided by the accelerator. To satisfy this criterion a routine method is proposed that uses therapy verification film exposed to the electron beam under a perspex wedge. The automatically processed film is then scanned with the densitometer of a beam data acquisition system (BDAS). The optical density versus distance plot is analysed using the BDAS computer that converts it to a quasi-depth dose curve and then calculates E O and E p,0 from the range parameters. The results for electron beams from console energies of 5 to 14 MeV show that the test criterion is within the capability of the method, and that the method is very practical for routine use in a quality assurance program. 9 refs., 5 tab., 2 figs

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

    International Nuclear Information System (INIS)

    Siegel, R.S.; Rae, J.L.; Ryan, N.L.; Edwards, C.; Fortune, W.P.; Lewis, R.J.; Reba, R.C.

    1989-01-01

    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

  17. Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: The effect of antibiotic treatment

    International Nuclear Information System (INIS)

    Chung, C.J.; Hicklin, O.A.; Payan, J.M.; Gordon, L.

    1991-01-01

    To determine the sensitivity and specificity of the indium-111-( 111 In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed. Of 41 consecutive 111 In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics. The average duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans for graft infection were found. By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%

  18. Detection of cervical cancer biomarker patterns in blood plasma and urine by differential scanning calorimetry and mass spectrometry.

    Science.gov (United States)

    Garbett, Nichola C; Merchant, Michael L; Helm, C William; Jenson, Alfred B; Klein, Jon B; Chaires, Jonathan B

    2014-01-01

    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 cervical cancer

  19. 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

  20. Methylation associated inactivation of RASSF1A and its synergistic effect with activated K-Ras in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Jing

    2009-12-01

    Full Text Available Abstract Background Epigenetic silencing of tumor suppressor genes associated with promoter methylation is considered to be a hallmark of oncogenesis. RASSF1A is a candidate tumor suppressor gene which was found to be inactivated in many human cancers. Although we have had a prelimilary cognition about the function of RASSF1A, the exact mechanisms about how RASSF1A functions in human cancers were largely unknown. Moreover, the effect of mutated K-Ras gene on the function of RASSF1A is lacking. The aim of this study was to investigate the expression profile and methylation status of RASSF1A gene, and to explore its concrete mechanisms as a tumor suppressor gene in Nasopharyngeal Carcinoma. Methods We examined the expression profile and methylation status of RASSF1A in two NPC cell lines, 38 primary nasopharyngeal carcinoma and 14 normal nasopharyngeal epithelia using RT-PCR and methylated specific PCR(MSP respectively. 5-aza-dC was then added to confirm the correlation between hypermethylation status and inactivation of RASSF1A. The NPC cell line CNE-2 was transfected with exogenous pcDNA3.1(+/RASSF1A plasmid in the presence or absence of mutated K-Ras by liposome-mediated gene transfer method. Flow cytometry was used to examine the effect of RASSF1A on cell cycle modulation and apoptosis. Meanwhile, trypan blue dye exclusion assays was used to detect the effect of RASSF1A transfection alone and the co-transfection of RASSF1A and K-Ras on cell proliferation. Results Promoter methylation of RASSF1A could be detected in 71.05% (27/38 of NPC samples, but not in normal nasopharyngeal epithelia. RASSF1A expression in NPC primary tumors was lower than that in normal nasopharyngeal epithelial (p p p p Conclusion Expression of RASSF1A is down-regulated in NPC due to the hypermethylation of promoter. Exogenous expression of RASSF1A is able to induce growth inhibition effect and apoptosis in tumor cell lines, and this effect could be enhanced by activated

  1. 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

  2. Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lin Jen-Der; Weng Hsiao-Fen; Lu Wen-Tsoung; Kao Pan-Fu; Huang Miau-Ju

    1998-01-01

    Radioactive iodine ( 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. 201 Tl has been deemed particularly useful in localizing metastases or recurrence in patients with a negative 131 I scan and abnormal levels of serum thyroglobulin (Tg). This study aimed to: (1) determine the value of 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 131 I and 201 Tl scintigraphy. Sixty-two thyroid remnant ablated patients who underwent simultaneous postoperative 201 Tl and 131 I scans and and serum Tg determinations were evaluated. Fifty patients had papillary thyroid carcinomas and 12 had follicular thyroid carcinomas. 201 Tl imaging was performed before the 131 I studies. Of the 62 patients who underwent 201 Tl imaging studies, 24 were found to have positive results, with local recurrence or distant metastases. Patients with positive results in the 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 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 201 Tl scans; one had a parotid tumour, one a periodontal abscess and one lung metastasis. Among the 38 patients with negative 201 Tl scans, 11 had positive findings on 131 I scans. Three had distant metastases: two with lung metastases and one with bone metastases. Patients with false-positive results on 131 I scans included those with biliary tract stones, ovarian cysts, and breast secretion. Of the 27 patients with negative 201 Tl and 131 I scans, 15 had elevated serum Tg levels. Among these, local recurrence followed by lung

  3. 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

  4. Detection of lacunar infarction in brain CT-scans: No evidence of bias from accompanying patient information

    International Nuclear Information System (INIS)

    Bonke, B.; Knippenberg, F.C.E. van; Duivenvoorden, H.J.; Kappelle, L.J.

    1989-01-01

    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. (orig.)

  5. EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

    Science.gov (United States)

    Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

    2016-04-01

    Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies

  6. 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.

  7. Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region.

    Science.gov (United States)

    Jang, Hyunbum; Abraham, Sherwin J; Chavan, Tanmay S; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I; Nussinov, Ruth; Gaponenko, Vadim

    2015-04-10

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    Science.gov (United States)

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  9. CMS-dependent prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer.

    Science.gov (United States)

    Smeby, J; Sveen, A; Merok, M A; Danielsen, S A; Eilertsen, I A; Guren, M G; Dienstmann, R; Nesbakken, A; Lothe, R A

    2018-05-01

    The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMSs) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600). A subset was analyzed for gene expression and confident CMS classification was obtained for 317 samples. This cohort was expanded with clinical and molecular data, including CMS classification, from 514 patients in the publically available dataset GSE39582. Gene expression signatures associated with KRAS and BRAFV600E mutations were used to evaluate differential impact of mutations on gene expression among the CMS groups. BRAFV600E and KRAS mutations were both associated with inferior 5-year overall survival (OS) exclusively in MSS tumors (BRAFV600E mutation versus KRAS/BRAF wild-type: Hazard ratio (HR) 2.85, P CMS1, leading to negative prognostic impact in this subtype (OS: BRAFV600E mutation versus wild-type: HR 7.73, P = 0.001). In contrast, the poor prognosis of KRAS mutations was limited to MSS tumors with CMS2/CMS3 epithelial-like gene expression profiles (OS: KRAS mutation versus wild-type: HR 1.51, P = 0.011). The subtype-specific prognostic associations were substantiated by differential effects of BRAFV600E and KRAS mutations on gene expression signatures according to the MSI status and CMS group. BRAFV600E mutations are enriched and associated with metastatic disease in CMS1 MSS tumors, leading to poor prognosis in this subtype. KRAS mutations are associated with adverse outcome in epithelial (CMS2/CMS3) MSS tumors.

  10. Kymogram detection and kymogram-correlated image reconstruction from subsecond spiral computed tomography scans of the heart

    International Nuclear Information System (INIS)

    Kachelriess, Marc; Sennst, Dirk-Alexander; Maxlmoser, Wolfgang; Kalender, Willi A.

    2002-01-01

    methods were observed. For one patient the synchronization information detected by the ECG monitor turned out to be wrong; here, the kymogram constituted the only approach that provided useful reconstructions. Patient studies with 12 and 16 slices indicate the usefulness of our approach for cone-beam CT scans. Kymogram-correlated reconstructions also appear to have the potential to improve imaging of pericardial lung areas in general

  11. Bone scans

    International Nuclear Information System (INIS)

    Hetherington, V.J.

    1989-01-01

    Oftentimes, in managing podiatric complaints, clinical and conventional radiographic techniques are insufficient in determining a patient's problem. This is especially true in the early stages of bone infection. Bone scanning or imaging can provide additional information in the diagnosis of the disorder. However, bone scans are not specific and must be correlated with clinical, radiographic, and laboratory evaluation. In other words, bone scanning does not provide the diagnosis but is an important bit of information aiding in the process of diagnosis. The more useful radionuclides in skeletal imaging are technetium phosphate complexes and gallium citrate. These compounds are administered intravenously and are detected at specific time intervals postinjection by a rectilinear scanner with minification is used and the entire skeleton can be imaged from head to toe. Minification allows visualization of the entire skeleton in a single image. A gamma camera can concentrate on an isolated area. However, it requires multiple views to complete the whole skeletal image. Recent advances have allowed computer augmentation of the data received from radionucleotide imaging. The purpose of this chapter is to present the current radionuclides clinically useful in podiatric patients

  12. Diagnostic performance of digital breast tomosynthesis with a wide scan angle compared to full-field digital mammography for the detection and characterization of microcalcifications

    International Nuclear Information System (INIS)

    Clauser, Paola; Nagl, Georg; Helbich, Thomas H.; Pinker-Domenig, Katja; Weber, Michael; Kapetas, Panagiotis; Bernathova, Maria; Baltzer, Pascal A.T.

    2016-01-01

    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.

  13. 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.

  14. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection

    International Nuclear Information System (INIS)

    LaMuraglia, G.M.; Fischman, A.J.; Strauss, H.W.; Keech, F.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Rubin, R.H.

    1989-01-01

    The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections

  15. Tc-99m-BrIDA hepatobiliary (HIDA) scan has a low sensitivity for detecting biliary complications after orthotopic liver transplantation in patients with hyperbilirubinemia

    International Nuclear Information System (INIS)

    Hopkins, L.O.; Feyssa, E.; Parsikia, A.; Khanmoradi, K.; Zaki, R.; Campos, S.; Araya, V.; Tran, H.; Ortiz, J.

    2011-01-01

    Tc-99m-BrIDA hepatobiliary scans are noninvasive tests for detecting biliary leaks and obstructions. However, there is low sensitivity and specificity in patients with hyperbilirubinemia. Biliary complications (BC) are the Achilles heel of orthotopic liver transplantation (OLT). We questioned whether hyperbilirubinemia in liver transplant recipients rendered HIDA scanning less dependable. HIDA findings were compared to endoscopic retrograde cholangiopancreatography, laparotomy, and clinical course. Results were categorized as follows: true positive (TP), true negative (TN), false positive (FP), false negative (FN), or nondiagnostic/inconclusive. We searched for variables associated with erroneous or nondiagnostic tests which we defined as all examinations determined to be FP, FN and/or nondiagnostic/inconclusive. Thirty-four patients underwent a HIDA scan. The sensitivity and specificity were 70 and 100%. The sensitivity of HIDA improved to 100% in patients with a total bilirubin (TB) 5 mg/dl. One FN had a TB <5 mg/dl, but was determined inconclusive due to the roux-en-Y. HIDA scans performed when the total bilirubin was <5 mg/dl had a high sensitivity and specificity for detecting biliary complications after OLT. However, when the total bilirubin exceeded 5 mg/dl, the specificity was still 100% but the numbers of nondiagnostic/inconclusive and FN exams were increased. (author)

  16. Detection of fatigue fracture in pearlitic flake graphite cast iron with the help of scanning and transmission electron microscopy

    International Nuclear Information System (INIS)

    Dunger, B.; Hunger, J.

    1976-01-01

    To prove the existence of the characteristic features of fatigue fracture in a pearlitic flake graphite cast iron, its fracture surface topography revealed by scanning electron microscopy has been compared with that of a pearlitic steel, the fractures having been caused by static tensile and by cyclic bending tests. The characteristic features of fatigue fracture were visible in the pearlitic matrix of the steel and of the flake graphite cast iron as well. These features differ characteristically from the lamellar structure of the pearlite, particularly after etching the surface area of the fractures. The graphite structures as viewed on the electron scanning and the electron transmission microscope are described. (orig.) [de

  17. Inhibition of beta-catenin and KRAS expressions by Piper betle in azoxymethane-induced colon cancer of male Fischer 344 rats.

    Science.gov (United States)

    Esa, Faezah; Ngah, Wan Zurinah Wan; Jamal, A Rahman A; Mohd Yusof, Yasmin Anum

    2013-12-01

    To investigate the chemopreventive effect of Piper betle (PB) on preneoplastic lesions (aberrant crypt foci [ACF]) induced by azoxymethane (AOM) in rats and its effect on colorectal cancer biomarkers (beta-catenin, KRAS, p53 and p21). A total of 32 male Fischer 344 rats were divided into phase 1 and phase 2 groups (8 and 24 weeks of AOM administration, respectively). Each phase was divided into 4 groups: control or normal saline (NS) (1 mL/kg), AOM (15 mg/kg body weight, once weekly for 2 weeks), PB (75 mg/kg body weight) and AOM + PB. PB was force-fed to rats a week after the second dose of AOM and NS. The colon was cut open longitudinally for methylene blue and immunohistochemistry staining. AOM administration showed formation of ACF at 8 and 24 weeks. PB, however, did not reduce ACF formation at either week, but it managed to reduce beta-catenin expression and KRAS found highly expressed in the AOM group of phase 1 rats. No immunoreactivities of p53 and p21 were detected in phase 2 rats, but instead inflammatory cells were visible in between the lesions. PB may act as a potential chemopreventive agent in the early stage of colon carcinogenesis by suppressing the expressions of beta-catenin and KRAS.

  18. 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.

  19. Concordance between myocardial perfusion scan assessed by SPECT and fractional flow reserve findings for detection of significant ischemia

    Directory of Open Access Journals (Sweden)

    Morteza Safi

    2016-09-01

    Conclusion: FFR and MPI with SPECT techniques showed significant concordance for detection of myocardial ischemia, regardless of the type of diseased coronary arteries. In this context, SPECT has high sensitivity and NPV for detection of ischemia compared with FFR.

  20. The Prognostic Impact of K-RAS Mutations in Adult Acute Myeloid Leukemia Patients Treated with High Dose Cytarabine

    International Nuclear Information System (INIS)

    Ahmad, E.I.; Gawish, H.H.; Al-Azizi, N.M.A.; El-Hefni, A.M.

    2009-01-01

    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 there is still controversy about its clinical relevance on the treatment outcome of 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 post induction consolidation chemotherapy in adult AML patients. Patients and Methods: The study comprised 71de novo AML patients with a male: Female ratio of 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 and K-RAS mutation detection using realtime PCR. The patients were randomized into 2 groups (gps) according to the ara-C dose used in consolidation treatment, HDAC gp receiving 400 mg ara-C and LDAC gp receiving 100 mg ara-C. They were followed over a period of 5 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). Blast cell percentage was significantly lower in mutRAS compared to wtRAS patients (p=<0.001). The M4 subtype of AML and cases with Inv 16 showed significantly higher frequencies in mutRAS compared to wtRAS patients, (p=0.015, 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 patients (p=0.326). Within the mutRAS patients treated with HDAC, cumulative OS was significantly higher than those treated with LDAC (p=0.001). This was not the case in the wtRAS group (p=0.285). There was no significant difference in disease The Prognostic Impact of K-RAS Mutations in Adult Acute Myeloid Leukemia Patients Treated with High Dose

  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. 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.

  3. PINPIN a-Si:H based structures for X-ray image detection using the laser scanning technique

    Science.gov (United States)

    Fernandes, M.; Vygranenko, Y.; Vieira, M.

    2015-05-01

    Conventional film based X-ray imaging systems are being replaced by their digital equivalents. Different approaches are being followed by considering direct or indirect conversion, with the later technique dominating. The typical, indirect conversion, X-ray panel detector uses a phosphor for X-ray conversion coupled to a large area array of amorphous silicon based optical sensors and a couple of switching thin film transistors (TFT). The pixel information can then be readout by switching the correspondent line and column transistors, routing the signal to an external amplifier. In this work we follow an alternative approach, where the electrical switching performed by the TFT is replaced by optical scanning using a low power laser beam and a sensing/switching PINPIN structure, thus resulting in a simpler device. The optically active device is a PINPIN array, sharing both front and back electrical contacts, deposited over a glass substrate. During X-ray exposure, each sensing side photodiode collects photons generated by the scintillator screen (560 nm), charging its internal capacitance. Subsequently a laser beam (445 nm) scans the switching diodes (back side) retrieving the stored charge in a sequential way, reconstructing the image. In this paper we present recent work on the optoelectronic characterization of the PINPIN structure to be incorporated in the X-ray image sensor. The results from the optoelectronic characterization of the device and the dependence on scanning beam parameters are presented and discussed. Preliminary results of line scans are also presented.

  4. 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 ...

  5. 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.

  6. Typhoid fever acquired in the United States, 1999–2010: epidemiology, microbiology, and use of a space–time scan statistic for outbreak detection

    Science.gov (United States)

    IMANISHI, M.; NEWTON, A. E.; VIEIRA, A. R.; GONZALEZ-AVILES, G.; KENDALL SCOTT, M. E.; MANIKONDA, K.; MAXWELL, T. N.; HALPIN, J. L.; FREEMAN, M. M.; MEDALLA, F.; AYERS, T. L.; DERADO, G.; MAHON, B. E.; MINTZ, E. D.

    2016-01-01

    SUMMARY Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection. PMID:25427666

  7. Typhoid fever acquired in the United States, 1999-2010: epidemiology, microbiology, and use of a space-time scan statistic for outbreak detection.

    Science.gov (United States)

    Imanishi, M; Newton, A E; Vieira, A R; Gonzalez-Aviles, G; Kendall Scott, M E; Manikonda, K; Maxwell, T N; Halpin, J L; Freeman, M M; Medalla, F; Ayers, T L; Derado, G; Mahon, B E; Mintz, E D

    2015-08-01

    Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

  8. PINPIN a-Si:H based structures for X-ray image detection using the laser scanning technique

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, M., E-mail: mfernandes@isel.pt [Electronics Telecommunication and Computer Dept., ISEL, R.Conselheiro Emídio Navarro, 1959-007 Lisboa (Portugal); CTS-UNINOVA Quinta da Torre, Monte da Caparica, 2829-516 Caparica (Portugal); Vygranenko, Y.; Vieira, M. [Electronics Telecommunication and Computer Dept., ISEL, R.Conselheiro Emídio Navarro, 1959-007 Lisboa (Portugal); CTS-UNINOVA Quinta da Torre, Monte da Caparica, 2829-516 Caparica (Portugal)

    2015-05-01

    Highlights: • We present novel structure for X-ray image sensor based on the laser scanned technique. • Amorphous silicon based tandem structure characterization results are presented and discussed. • Results from preliminary tests of the imaging application are promising for very large area image sensing. - Abstract: Conventional film based X-ray imaging systems are being replaced by their digital equivalents. Different approaches are being followed by considering direct or indirect conversion, with the later technique dominating. The typical, indirect conversion, X-ray panel detector uses a phosphor for X-ray conversion coupled to a large area array of amorphous silicon based optical sensors and a couple of switching thin film transistors (TFT). The pixel information can then be readout by switching the correspondent line and column transistors, routing the signal to an external amplifier. In this work we follow an alternative approach, where the electrical switching performed by the TFT is replaced by optical scanning using a low power laser beam and a sensing/switching PINPIN structure, thus resulting in a simpler device. The optically active device is a PINPIN array, sharing both front and back electrical contacts, deposited over a glass substrate. During X-ray exposure, each sensing side photodiode collects photons generated by the scintillator screen (560 nm), charging its internal capacitance. Subsequently a laser beam (445 nm) scans the switching diodes (back side) retrieving the stored charge in a sequential way, reconstructing the image. In this paper we present recent work on the optoelectronic characterization of the PINPIN structure to be incorporated in the X-ray image sensor. The results from the optoelectronic characterization of the device and the dependence on scanning beam parameters are presented and discussed. Preliminary results of line scans are also presented.

  9. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.

    Science.gov (United States)

    Yun, Jihye; Mullarky, Edouard; Lu, Changyuan; Bosch, Kaitlyn N; Kavalier, Adam; Rivera, Keith; Roper, Jatin; Chio, Iok In Christine; Giannopoulou, Eugenia G; Rago, Carlo; Muley, Ashlesha; Asara, John M; Paik, Jihye; Elemento, Olivier; Chen, Zhengming; Pappin, Darryl J; Dow, Lukas E; Papadopoulos, Nickolas; Gross, Steven S; Cantley, Lewis C

    2015-12-11

    More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations. Copyright © 2015, American Association for the Advancement of Science.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Detection of delamination defects in plate type fuel elements applying an automated C-Scan ultrasonic system

    International Nuclear Information System (INIS)

    Katchadjian, P.; Desimone, C.; Ziobrowski, C.; Garcia, A.

    2002-01-01

    For the inspection of plate type fuel elements to be used in Research Nuclear Reactors it was applied an immersion pulse-echo ultrasonic technique. For that reason an automated movement system was implemented according to the axes X, Y and Z that allows to automate the test and to show the results obtained in format of C-Scan, facilitating the immediate identification of possible defects and making repetitive the inspection. In this work problems found during the laboratory tests and factors that difficult the inspection are commented. Also the results of C-Scans over UMo fuel elements with pattern defects are shown. Finally, the main characteristics of the transducer with the one the better results were obtained are detailed. (author)

  15. 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.

  16. KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.

    Science.gov (United States)

    Camaj, Peter; Primo, Stefano; Wang, Yan; Heinemann, Volker; Zhao, Yue; Laubender, Ruediger Paul; Stintzing, Sebastian; Giessen-Jung, Clemens; Jung, Andreas; Gamba, Sebastian; Bruns, Christiane Josephine; Modest, Dominik Paul

    2015-01-01

    To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells. Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo. Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants. In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib.

  17. Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

    2007-01-01

    Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

  18. 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.

  19. 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

  20. 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.

  1. Detection of a new 'nematic-like' phase in liquid crystal-amphiphile mixture by differential scanning calorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Dan, Kaustabh, E-mail: kaustabhdan@gmail.com; Roy, Madhusudan, E-mail: kaustabhdan@gmail.com; Datta, Alokmay, E-mail: kaustabhdan@gmail.com [Surface Physics and Materials Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar Block, Sector 1, Kolkata-700064 (India)

    2014-04-24

    Differential Scanning Calorimetry (DSC) studies on phase transitions of the pure liquid crystalline material N-4-methoxybenzylidene-4-butylaniline (MBBA) and mixtures of MBBA and the amphiphile Stearic Acid (StA) show significant changes in the behavior of mixture from pure MBBA, as regards the nematic-isotropic (N-I) transition temperature (T{sub c}) and other thermodynamic parameters like enthalpy, specific heat and activation energy with concentration of StA. In particular, the convexity of the Arrhenius plot in pure MBBA vanishes with StA concentration pointing to the formation of a new, perhaps 'nematic-like', phase in the mixtures.

  2. Use of multidetector-row computed tomography scan to detect pannus formation in prosthetic mechanical aortic valves.

    Science.gov (United States)

    Aladmawi, Mohamed A; Pragliola, Claudio; Vriz, Olga; Galzerano, Domenico

    2017-04-01

    Obstruction of a mechanical aortic valve by pannus formation at the subvalvular level is a major long-term complication of aortic valve replacement (AVR). In fact, pannus is sometime difficult to differentiate from patient-prosthesis mismatch or valve thrombosis. In most cases cine-angiography and echocardiography, either transthoracic or transesophageal, cannot correctly visualize the complication when the leaflets show a normal mobility. Recent technological refinements made this difficult diagnosis possible by ECG-gated computed tomography (CT) scan which shows adequate images in 90% of the cases and can differentiate pannus from fresh and organized thrombus.

  3. 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

    International Nuclear Information System (INIS)

    Byun, Byung Hyun; Urn, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Lee, Byeong Cheol; Lee, Guk Haeng; Lee, Yong Sik; Shim, Youn Sang

    2007-01-01

    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

  4. 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

  5. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    International Nuclear Information System (INIS)

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    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 2 weekly and 1650 mg/m 2 /day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m 2 on 1 week before radiation, and 250 mg/m 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 irinotecan plus

  6. 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.

  7. The higher level of complexity of K-Ras4B activation at the membrane

    Science.gov (United States)

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  8. The higher level of complexity of K-Ras4B activation at the membrane.

    Science.gov (United States)

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-04-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5'-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.-Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. © FASEB.

  9. 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.

  10. Early detection of lung cancer using ultra-low-dose computed tomography in coronary CT angiography scans among patients with suspected coronary heart disease.

    Science.gov (United States)

    Zanon, Matheus; Pacini, Gabriel Sartori; de Souza, Vinicius Valério Silveiro; Marchiori, Edson; Meirelles, Gustavo Souza Portes; Szarf, Gilberto; Torres, Felipe Soares; Hochhegger, Bruno

    2017-12-01

    To assess whether an additional chest ultra-low-dose CT scan to the coronary CT angiography protocol can be used for lung cancer screening among patients with suspected coronary artery disease. 175 patients underwent coronary CT angiography for assessment of coronary artery disease, additionally undergoing ultra-low-dose CT screening to early diagnosis of lung cancer in the same scanner (80kVp and 15mAs). Patients presenting pulmonary nodules were followed-up for two years, repeating low-dose CTs in intervals of 3, 6, or 12 months based on nodule size and growth rate in accordance with National Comprehensive Cancer Network guidelines. Ultra-low-dose CT identified 71 patients with solitary pulmonary nodules (41%), with a mean diameter of 5.50±4.00mm. Twenty-eight were >6mm, and in 79% (n=22) of these cases they were false positive findings, further confirmed by follow-up (n=20), resection (n=1), or biopsy (n=1). Lung cancer was detected in six patients due to CT screening (diagnostic yield: 3%). Among these, four cases could not be detected in the cardiac field of view. Most patients were in early stages of the disease. Two patients diagnosed at advanced stages died due to cancer complications. The addition of the ultra-low-dose CT scan represented a radiation dose increment of 1.22±0.53% (effective dose, 0.11±0.03mSv). Lung cancer might be detected using additional ultra-low-dose protocols in coronary CT angiography scans among patients with suspected coronary artery disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Detection of Clostridium difficile infection clusters, using the temporal scan statistic, in a community hospital in southern Ontario, Canada, 2006-2011.

    Science.gov (United States)

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

    2014-05-12

    In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital. Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases. Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007-2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023). Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital

  12. Model PET Scan Activity

    Science.gov (United States)

    Strunk, Amber; Gazdovich, Jennifer; Redouté, Oriane; Reverte, Juan Manuel; Shelley, Samantha; Todorova, Vesela

    2018-05-01

    This paper provides a brief introduction to antimatter and how it, along with other modern physics topics, is utilized in positron emission tomography (PET) scans. It further describes a hands-on activity for students to help them gain an understanding of how PET scans assist in detecting cancer. Modern physics topics provide an exciting way to introduce students to current applications of physics.

  13. Septal endocarditis, bone infection and severe leg ischemia detected in Tc-99m labelled monoclonal anti granulocyte scan

    International Nuclear Information System (INIS)

    Bechelaghem, A.I; Habbeche, M; Benlabgaa, R; Ghedbane, IE; Hanzal, A; Khelifa, A; Mechcken, F; Bourezak, SE; Bouyoucef, SE

    2006-01-01

    Patient 28 years old has continued to have a persistent fever (39.2 O C), despite ten days treatment by specific antibiotics for bacterial endocarditis associated to a recent claudication of the right lower leg. The persistent fever has motivated a 99mTc-labelled monoclonal anti granulocyte scan which has showed an important uptake in the myocardial septum, and other infection locations in temporal bone and in right tibial arteries. Two days after, a nanocolloids-99mTc WBS showed no uptake in the heart area, a total absence of uptake of the nanocolloids in the bone marrow of right tibia b and cranial SPECT views confirmed the infectious site in the right temporal bone. New antibiotic strategy was adopted successfully associated with surgical amputation of the right lower leg (au)

  14. CutL: an alternative to Kulldorff's scan statistics for cluster detection with a specified cut-off level.

    Science.gov (United States)

    Więckowska, Barbara; Marcinkowska, Justyna

    2017-11-06

    When searching for epidemiological clusters, an important tool can be to carry out one's own research with the incidence rate from the literature as the reference level. Values exceeding this level may indicate the presence of a cluster in that location. This paper presents a method of searching for clusters that have significantly higher incidence rates than those specified by the investigator. The proposed method uses the classic binomial exact test for one proportion and an algorithm that joins areas with potential clusters while reducing the number of multiple comparisons needed. The sensitivity and specificity are preserved by this new method, while avoiding the Monte Carlo approach and still delivering results comparable to the commonly used Kulldorff's scan statistics and other similar methods of localising clusters. A strong contributing factor afforded by the statistical software that makes this possible is that it allows analysis and presentation of the results cartographically.

  15. 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, ...

  16. Tomographic scanning apparatus

    International Nuclear Information System (INIS)

    1981-01-01

    This patent specification relates to a tomographic scanning apparatus using a fan beam and digital output signal, and particularly to the design of the gas-pressurized ionization detection system. (U.K.)

  17. Detection of intermittent resistive faults in electronic systems based on the mixed-signal boundary-scan standard

    NARCIS (Netherlands)

    Kerkhoff, Hans G.; Ebrahimi, Hassan

    2015-01-01

    In avionics, like glide computers, the problem of No Faults Found (NFF) is a very serious and extremely costly affair. The rare occurrences and short bursts of these faults are the most difficult ones to detect and diagnose in the testing arena. Several techniques are now being developed in ICs by

  18. 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.

  19. Targeting the PI3K signaling pathway in KRAS mutant colon cancer

    International Nuclear Information System (INIS)

    Hong, Suntaek; Kim, SoYoung; Kim, Hye Youn; Kang, Myunghee; Jang, Ho Hee; Lee, Won-Suk

    2015-01-01

    Metastatic colorectal cancer (CRC) patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide-3-kinase (PIK3CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations (DLD-1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration-dependent manner in the LoVo (PI3KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells (PIK3CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone (P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation

  20. 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.

  1. 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

    2016-01-01

    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. PMID:27702896

  2. Scanning of bone metastases

    International Nuclear Information System (INIS)

    Robillard, J.

    1977-01-01

    The Centers against cancer of Caen, Angers, Montpellier, Strasbourg and 'the Curie Foundation' have confronted their experience in detection of bone metastases by total body scanning. From the investigation by this procedure, of 1,467 patients with cancer, it results: the confrontation between radio and scanning shows a rate of false positive and false negative identical to the literature ones; the countage scanning allows to reduce the number of false positive; scanning allows to direct bone biopsy and to improve efficiency of histological examination [fr

  3. New pediatric vision screener employing polarization-modulated, retinal-birefringence-scanning-based strabismus detection and bull's eye focus detection with an improved target system: opto-mechanical design and operation

    Science.gov (United States)

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

    2014-06-01

    Amblyopia ("lazy eye") is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia's primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull's eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.

  4. New pediatric vision screener employing polarization-modulated, retinal-birefringence-scanning-based strabismus detection and bull's eye focus detection with an improved target system: opto-mechanical design and operation.

    Science.gov (United States)

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

    2014-06-01

    Amblyopia ("lazy eye") is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia's primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull's eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.

  5. Diagnostic accuracy of cone-beam computed tomography scans with high- and low-resolution modes for the detection of root perforations.

    Science.gov (United States)

    Shokri, Abbas; Eskandarloo, Amir; Norouzi, Marouf; Poorolajal, Jalal; Majidi, Gelareh; Aliyaly, Alireza

    2018-03-01

    This study compared the diagnostic accuracy of cone-beam computed tomography (CBCT) scans obtained with 2 CBCT systems with high- and low-resolution modes for the detection of root perforations in endodontically treated mandibular molars. The root canals of 72 mandibular molars were cleaned and shaped. Perforations measuring 0.2, 0.3, and 0.4 mm in diameter were created at the furcation area of 48 roots, simulating strip perforations, or on the external surfaces of 48 roots, simulating root perforations. Forty-eight roots remained intact (control group). The roots were filled using gutta-percha (Gapadent, Tianjin, China) and AH26 sealer (Dentsply Maillefer, Ballaigues, Switzerland). The CBCT scans were obtained using the NewTom 3G (QR srl, Verona, Italy) and Cranex 3D (Soredex, Helsinki, Finland) CBCT systems in high- and low-resolution modes, and were evaluated by 2 observers. The chi-square test was used to assess the nominal variables. In strip perforations, the accuracies of low- and high-resolution modes were 75% and 83% for NewTom 3G and 67% and 69% for Cranex 3D. In root perforations, the accuracies of low- and high-resolution modes were 79% and 83% for NewTom 3G and was 56% and 73% for Cranex 3D. The accuracy of the 2 CBCT systems was different for the detection of strip and root perforations. The Cranex 3D had non-significantly higher accuracy than the NewTom 3G. In both scanners, the high-resolution mode yielded significantly higher accuracy than the low-resolution mode. The diagnostic accuracy of CBCT scans was not affected by the perforation diameter.

  6. Using 99mTc-DTPA radioaerosol inhalation lung scan as compared with computed tomography to detect lung injury in blunt chest trauma

    International Nuclear Information System (INIS)

    Esme, H.; Kaya, E.; Solak, O.; Yavuz, Y.; Yurumez, Y.; Sezer, M.

    2007-01-01

    Detection of pulmonary contusion in patients with blunt chest trauma is very important so as to commence therapy immediately to avoid irreversible damage. The purpose of our study was to evaluate the efficacy of technetium-99m diethylene triamine penta-acetic acid ( 99m Tc-DTPA) aerosol inhalation lung scintigraphy in comparison with chest computed tomography (CT) in the diagnosis of pulmonary contusion at acute blunt chest trauma. Twenty-nine patients with isolated blunt chest trauma were referred to the emergency department of our hospital, and nine healthy people participated in this study. Sixteen patients who had pulmonary contusion on CT scans were referred to as group 1, and 13 patients who had normal CT scans as group 2. Nine healthy people comprised a control group. 99m Tc-DTPA aerosol inhalation lung scintigraphy was performed on the first day in all patients. The mean half time (T 1/2 ) and penetration index values of 99m Tc-DTPA clearance were significantly lower in groups 1 and 2 compared with the control group. Among the three groups, there were no significant differences in arterial blood gas analysis except for PO 2 . The mean T 1/2 value of 99m Tc-DTPA clearance did correlate with PO 2 values but not with pH, PCO 2 , or HCO 3 values. 99m Tc-DTPA radioaerosol inhalation lung imaging may serve as a useful adjunct and supportive method to chest CT scanning for detecting mild pulmonary contusion. (author)

  7. Path scanning for the detection of anomalous subgraphs and use of DNS requests and host agents for anomaly/change detection and network situational awareness

    Science.gov (United States)

    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.

  8. 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...

  9. Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study

    NARCIS (Netherlands)

    Krens, Lisanne L.; Simkens, Lieke H. J.; Baas, Jara M.; Koomen, Els R.; Gelderblom, Hans; Punt, Cornelis J. A.; Guchelaar, Henk-Jan

    2014-01-01

    Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with

  10. 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.

  11. Characterization of a novel oncogenic K-ras mutation in colon cancer

    International Nuclear Information System (INIS)

    Akagi, Kiwamu; Uchibori, Ryosuke; Yamaguchi, Kensei; Kurosawa, Keiko; Tanaka, Yoichiro; Kozu, Tomoko

    2007-01-01

    Activating mutations of RAS are frequently observed in subsets of human cancers, indicating that RAS activation is involved in tumorigenesis. Here, we identified and characterized a novel G to T transversion mutation of the K-ras gene at the third position of codon 19 (TTG) which substituted phenylalanine for leucine in 3 primary colon carcinomas. Biological and biochemical activity was examined using transformed NIH3T3 cells expressing mutant or wild-type K-ras. Transformants harboring the K-ras mutation at codon 19 showed proliferative capacity under serum-starved conditions, less contact inhibition, anchorage-independent growth, tumorigenicity in nude mice and elevation of active Ras-GTP levels. These results indicated that this novel mutation possesses high oncogenic activity

  12. The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice

    International Nuclear Information System (INIS)

    Plowman, Sarah J.; Arends, Mark J.; Brownstein, David G.; Luo Feijun; Devenney, Paul S.; Rose, Lorraine; Ritchie, Ann-Marie; Berry, Rachel L.; Harrison, David J.; Hooper, Martin L.; Patek, Charles E.

    2006-01-01

    Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras tmΔ4A/tmΔ4A (exon 4A knock-out) ES cells which express K-ras4B only and K-ras -/- (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras tmΔ4A/tmΔ4A mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras tmΔ4A/tmΔ4A ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras tmΔ4A/tmΔ4A and K-ras -/- ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras -/- cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras tmΔ4A/tmΔ4A ES cells were more resistant to etoposide-induced apoptosis than K-ras -/- cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice

  13. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    DEFF Research Database (Denmark)

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced......), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11...... SBT/APST-implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non-invasive and invasive) pairs (p identical KRAS or BRAF...

  14. 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.

  15. Automated detection and volumetric segmentation of the spleen in CT scans; Automatische Detektion und volumetrische Segmentierung der Milz in CT-Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Hammon, M.; Dankerl, P.; Janka, R.; Uder, M.; Cavallaro, A. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.; Kramer, M.; Seifert, S.; Tsymbal, A.; Costa, M.J. [Siemens AG, Erlangen (Germany). Corporate Technology

    2012-08-15

    To introduce automated detection and volumetric segmentation of the spleen in spiral CT scans with the THESEUS-MEDICO software. The consistency between automated volumetry (aV), estimated volume determination (eV) and manual volume segmentation (mV) was evaluated. Retrospective evaluation of the CAD system based on methods like ''marginal space learning'' and ''boosting algorithms''. 3 consecutive spiral CT scans (thoraco-abdominal; portal-venous contrast agent phase; 1 or 5 mm slice thickness) of 15 consecutive lymphoma patients were included. The eV: 30 cm{sup 3} + 0.58 (width x length x thickness of the spleen) and the mV as the reference standard were determined by an experienced radiologist. The aV could be performed in all CT scans within 15.2 ({+-} 2.4) seconds. The average splenic volume measured by aV was 268.21 {+-} 114.67 cm{sup 3} compared to 281.58 {+-} 130.21 cm{sup 3} in mV and 268.93 {+-} 104.60 cm{sup 3} in eV. The correlation coefficient was 0.99 (coefficient of determination (R{sup 2}) = 0.98) for aV and mV, 0.91 (R{sup 2} = 0.83) for mV and eV and 0.91 (R{sup 2} = 0.82) for aV and eV. There was an almost perfect correlation of the changes in splenic volume measured with the new aV and mV (0.92; R{sup 2} = 0.84), mV and eV (0.95; R{sup 2} = 0.91) and aV and eV (0.83; R{sup 2} = 0.69) between two time points. The automated detection and volumetric segmentation software rapidly provides an accurate measurement of the splenic volume in CT scans. Knowledge about splenic volume and its change between two examinations provides valuable clinical information without effort for the radiologist. (orig.)

  16. 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.

  17. 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

  18. The impact of KRAS mutations on VEGF-A production and tumour vascular network

    International Nuclear Information System (INIS)

    Figueras, Agnès; Arbos, Maria Antonia; Quiles, Maria Teresa; Viñals, Francesc; Germà, Josep Ramón; Capellà, Gabriel

    2013-01-01

    The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile. Codon13 KRAS mutation (ASP13) or codon12 KRAS mutation (CYS12) NIH3T3 transfectants were analyzed in vitro and in vivo. Expression of HIF-1α, and VEGF-A was studied at RNA and protein levels. Regulation of VEGF-A promoter activity was assessed by means of luciferase assays using different plasmid constructs. Vascular network was assessed in tumors growing after subcutaneous inoculation. Non parametric statistics were used for analysis of results. Our results show that in normoxic conditions ASP13 transfectants exhibited less HIF-1α protein levels and activity than CYS12. In contrast, codon 13 transfectants exhibited higher VEGF-A mRNA and protein levels and enhanced VEGF-A promoter activity. These differences were due to a differential activation of Sp1/AP2 transcription elements of the VEGF-A promoter associated with increased ERKs signalling in ASP13 transfectants. Subcutaneous CYS12 tumours expressed less VEGF-A and showed a higher microvessel density (MVD) than ASP13 tumours. In contrast, prominent vessels were only observed in the latter. Subtle changes in the molecular nature of KRAS oncogene activating mutations occurring in tumour cells have a major impact on the vascular strategy devised providing with new insights on the role of KRAS mutations on angiogenesis

  19. Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods.

    Directory of Open Access Journals (Sweden)

    Yuri Tani Utsunomiya

    Full Text Available As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP data generated from dairy and beef cattle (taurine and indicine. The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7 population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3 in Brown Swiss (P = 3.82×10(-12, and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

  20. Nove interpretacije fluvialnih sedimentov na krasu = New interpretations of fluvial sediments from the Kras

    Directory of Open Access Journals (Sweden)

    Andrej Mihevc

    2007-01-01

    Full Text Available Important unroofed caves with fluvial sediments from Divaški kras, Matarsko podoljePodgorski kras are presented. Extend of the phenomena and relation to the existingand karst surface and geomorphological meaning of them are described. Sedimentsthem were analysed and dated with different methods. The largest age of the sedimentfound in the unroofed cave excavated in Črnotiče quarry. In the cave wall fossil remainsstygobiont Marifugia cavatica were covered by 3.2-4.1 Ma old fluvial sediments.

  1. Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.

    Science.gov (United States)

    Cheon, Eric C; Strouch, Matthew J; Barron, Morgan R; Ding, Yongzeng; Melstrom, Laleh G; Krantz, Seth B; Mullapudi, Bhargava; Adrian, Kevin; Rao, Sambasiva; Adrian, Thomas E; Bentrem, David J; Grippo, Paul J

    2011-06-15

    Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid. Copyright © 2010 UICC.

  2. Evaluation of bone scan by scintigraphy to detect subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Baker, H.L.; Woodbury, D.H.; Krause, C.J.; Saxon, K.G.; Stewart, R.C.

    1982-01-01

    A prospective study using scintigraphy was performed to compare the sensitivity of the Panorex roentgenogram and the bone scan in detecting subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity and floor of the mouth. Twenty-five patients with squamous cell carcinoma of the floor of the mouth were evaluated preoperatively by both the Panorex and scintigraphic techniques and the results compared with postoperative pathologic findings. In 13 (52%) of the cases, Panorex and scintigraphic techniques were comparable in detecting tumor involvement in bone. In eight cases (32%) all three modalities had normal pathologic indications of the mandible. However, in four cases (16%) results of the scintigraphic techniques were abnormal and the Panorex, normal. In four separate cases, the extent of lesion demonstrable by scintiscanning was greater than delineated by Panorex; surgical specimen confirmed this finding. Pathologic examination of operative specimens confirmed tumor involvement. These data lead us to believe that the scintigraphic techniques may be more sensitive in detecting early mandibular involvement with squamous cell carcinoma than the Panorex technique and may help alter the therapeutic approach

  3. Reliability of the MicroScan WalkAway PC21 panel in identifying and detecting oxacillin resistance in clinical coagulase-negative staphylococci strains.

    Science.gov (United States)

    Olendzki, A N; Barros, E M; Laport, M S; Dos Santos, K R N; Giambiagi-Demarval, M

    2014-01-01

    The purpose of this study was to determine the reliability of the MicroScan WalkAway PosCombo21 (PC21) system for the identification of coagulase-negative staphylococci (CNS) strains and the detection of oxacillin resistance. Using molecular and phenotypic methods, 196 clinical strains were evaluated. The automated system demonstrated 100 % reliability for the identification of the clinical strains Staphylococcus haemolyticus, Staphylococcus hominis and Staphylococcus cohnii; 98.03 % reliability for the identification of Staphylococcus epidermidis; 70 % reliability for the identification of Staphylococcus lugdunensis; 40 % reliability for the identification of Staphylococcus warneri; and 28.57 % reliability for the identification of Staphylococcus capitis, but no reliability for the identification of Staphylococcus auricularis, Staphylococcus simulans and Staphylococcus xylosus. We concluded that the automated system provides accurate results for the more common CNS species but often fails to accurately identify less prevalent species. For the detection of oxacillin resistance, the automated system showed 100 % specificity and 90.22 % sensitivity. Thus, the PC21 panel detects oxacillin-resistant strains, but is limited by the heteroresistance that is observed when using most phenotypic methods.

  4. 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.

  5. Assessment of Quadrivalent Human Papillomavirus Vaccine Safety Using the Self-Controlled Tree-Temporal Scan Statistic Signal-Detection Method in the Sentinel System.

    Science.gov (United States)

    Yih, W Katherine; Maro, Judith C; Nguyen, Michael; Baker, Meghan A; Balsbaugh, Carolyn; Cole, David V; Dashevsky, Inna; Mba-Jonas, Adamma; Kulldorff, Martin

    2018-06-01

    The self-controlled tree-temporal scan statistic-a new signal-detection method-can evaluate whether any of a wide variety of health outcomes are temporally associated with receipt of a specific vaccine, while adjusting for multiple testing. Neither health outcomes nor postvaccination potential periods of increased risk need be prespecified. Using US medical claims data in the Food and Drug Administration's Sentinel system, we employed the method to evaluate adverse events occurring after receipt of quadrivalent human papillomavirus vaccine (4vHPV). Incident outcomes recorded in emergency department or inpatient settings within 56 days after first doses of 4vHPV received by 9- through 26.9-year-olds in 2006-2014 were identified using International Classification of Diseases, Ninth Revision, diagnosis codes and analyzed by pairing the new method with a standard hierarchical classification of diagnoses. On scanning diagnoses of 1.9 million 4vHPV recipients, 2 statistically significant categories of adverse events were found: cellulitis on days 2-3 after vaccination and "other complications of surgical and medical procedures" on days 1-3 after vaccination. Cellulitis is a known adverse event. Clinically informed investigation of electronic claims records of the patients with "other complications" did not suggest any previously unknown vaccine safety problem. Considering that thousands of potential short-term adverse events and hundreds of potential risk intervals were evaluated, these findings add significantly to the growing safety record of 4vHPV.

  6. 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.

  7. One-step simultaneous differential scanning calorimetry-FTIR microspectroscopy to quickly detect continuous pathways in the solid-state glucose/asparagine Maillard reaction.

    Science.gov (United States)

    Hwang, Deng-Fwu; Hsieh, Tzu-Feng; Lin, Shan-Yang

    2013-01-01

    The stepwise reaction pathway of the solid-state Maillard reaction between glucose (Glc) and asparagine (Asn) was investigated using simultaneous differential scanning calorimetry (DSC)-FTIR microspectroscopy. The color change and FTIR spectra of Glc-Asn physical mixtures (molar ratio = 1:1) preheated to different temperatures followed by cooling were also examined. The successive reaction products such as Schiff base intermediate, Amadori product, and decarboxylated Amadori product in the solid-state Glc-Asn Maillard reaction were first simultaneously evidenced by this unique DSC-FTIR microspectroscopy. The color changed from white to yellow-brown to dark brown, and appearance of new IR peaks confirmed the formation of Maillard reaction products. The present study clearly indicates that this unique DSC-FTIR technique not only accelerates but also detects precursors and products of the Maillard reaction in real time.

  8. 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

  9. A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells

    International Nuclear Information System (INIS)

    Mouron, Silvana Andrea; Grillo, Claudia Alejandra; Dulout, Fernando Noel; Golijow, Carlos Daniel

    2004-01-01

    Cadmium (Cd) is a toxic heavy metal of continuing occupational and environmental concern with a wide variety of adverse effects. Several studies have shown that cadmium produces DNA strand breaks, DNA-protein cross-links, oxidative DNA damage, chromosomal aberrations, dysregulation of gene expression resulting in enhanced proliferation, depressed apoptosis and/or altered DNA repair. This study was undertaken to investigate the ability of cadmium chloride (CdCl 2 ) and cadmium sulphate (CdSO 4 ) to induce point mutations in codon 12 of the K-ras protooncogene assessed by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and RFLP-enriched PCR methods. Also their genotoxic effects were analyzed by the comet assay and sister chromatid exchanges test. The human lung fibroblast cell line MRC-5 was used for the experiments. Sister chromatid exchanges assay (SCEs) frequencies were significantly increased in cells exposed to cadmium salts in relation to controls (p < 0.001). Despite the slow increment observed in the three comet parameters considered when cells were treated with cadmium chloride, significant differences between groups were only found in the variable comet moment (CM) (p < 0.005). On the other hand, when cells were exposed to cadmium sulphate, the Kruskal-Wallis test showed highly significant differences between groups for migration, tail moment and comet moment parameters (p < 0.001). Nevertheless, a null or weak point mutation induction in K-ras protooncogene was detected using polymerase chain reaction-low ionic strength-single strand conformation polymorphisms (PCR-LIS-SSCP) and RFLP-enriched PCR methods when cells were treated with cadmium salts. Thus, inorganic cadmium produces genotoxicity in human lung fibroblast MRC-5 cells, in the absence of significant point mutation of the K-ras gene

  10. p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

    International Nuclear Information System (INIS)

    Tierney, L.A.; Hahn, F.F.; Lechner, J.F.

    1996-01-01

    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 239 PuO 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 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 239 PuO 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

  11. 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.

  12. H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the Same Regulatory Sequences.

    Science.gov (United States)

    Drosten, Matthias; Simón-Carrasco, Lucía; Hernández-Porras, Isabel; Lechuga, Carmen G; Blasco, María T; Jacob, Harrys K C; Fabbiano, Salvatore; Potenza, Nicoletta; Bustelo, Xosé R; Guerra, Carmen; Barbacid, Mariano

    2017-02-01

    Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-Ras G12V oncogene sequences. Germline expression of H-Ras G12V or K-Ras G12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes. Whereas H-Ras G12V elicited papillomas and hematopoietic tumors, K-Ras G12V induced lung tumors and gastric lesions. Pulmonary expression of H-Ras G12V created a senescence-like state caused by excessive MAPK signaling. Likewise, H-Ras G12V but not K-Ras G12V induced senescence in mouse embryonic fibroblasts. Label-free quantitative analysis revealed that minor differences in H-Ras G12V expression levels led to drastically different biological outputs, suggesting that subtle differences in MAPK signaling confer nonequivalent functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res; 77(3); 707-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. 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); 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. Collée (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. dos Santos Silva (Isabel); 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,

  14. 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. W...

  15. 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

  16. Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

    NARCIS (Netherlands)

    Kampman, E.; Voskuil, D.W.; Kraats, A.A. van; Balder, H.F.; Muijen, G.N.P. van; Goldbohm, R.A.; Veer, P. van 't

    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% harboured mutations, of which 82% were located in codon 12. High intakes of animal protein, calcium and poultry were differently

  17. KRAS Mutation and Epithelial-Macrophage Interplay in Pancreatic Neoplastic Transformation.

    Science.gov (United States)

    Bishehsari, Faraz; Zhang, Lijuan; Barlass, Usman; Preite, Nailliw; Turturro, Sanja; Najor, Matthew S; Shetuni, Brandon B; Zayas, Janet P; Mahdavinia, Mahboobeh; Abukhdeir, Abde M; Keshavarzian, Ali

    2018-05-14

    Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased i) ductal to acinar gene expression ratios, ii) epithelial cells proliferation, and iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo. KRAS mutations induced a pro-tumorigenic phenotype in macrophages. Altered macrophages decreased epithelial Pigment Epithelial Derived Factor (PEDF) expression and induced a cancerous phenotype. We validated our findings using annotated patient samples from The Cancer Genome Atlas (TCGA) as well as in our human PDA specimens. Epithelium-macrophage cross talk occurs early in pancreatic carcinogenesis where KRAS directly induces cancer-related phenotypes in epithelium, and also promotes a pro-tumorigenic phenotype in macrophages, in turn augmenting neoplastic growth. This article is protected by copyright. All rights reserved. © 2018 UICC.

  18. The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

    DEFF Research Database (Denmark)

    Pharoah, Paul D P; Palmieri, Rachel T; Ramus, Susan J

    2011-01-01

    PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a cand...

  19. Fbxw7 Deletion Accelerates KrasG12D-Driven Pancreatic Tumorigenesis via Yap Accumulation.

    Science.gov (United States)

    Zhang, Qiang; Zhang, Yaqing; Parsels, Joshua D; Lohse, Ines; Lawrence, Theodore S; Pasca di Magliano, Marina; Sun, Yi; Morgan, Meredith A

    2016-11-01

    Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras G12D ;Fbxw7 fl/fl (KFC fl/fl ) compound mice. We found that KFC fl/fl mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age. PDA in KFC fl/fl mice was preceded by earlier onset of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) lesions, and associated with chromosomal instability and the accumulation of Fbxw7 substrates Yes-associated protein (Yap), c-Myc, and Notch. Using KFC fl/fl and FBXW7-deficient human pancreatic cancer cells, we found that Yap silencing attenuated growth promotion by Fbxw7 deletion. Our data demonstrate that Fbxw7 is a potent suppressor of Kras G12D -induced pancreatic tumorigenesis due, at least in part, to negative regulation of Yap. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery

    International Nuclear Information System (INIS)

    Derbel, Olfa; La Fouchardière, Christelle de; Wang, Qing; Desseigne, Françoise; Rivoire, Michel; Meeus, Pierre; Peyrat, Patrice; Stella, Mattia; Martel-Lafay, Isabelle; Lemaistre, Anne-Isabelle

    2013-01-01

    Conventional treatment for locally advanced rectal cancer usually combines neoadjuvant radiochemotherapy and surgery. Until recently, there have been limited predictive factors (clinical or biological) for rectal tumor response to conventional treatment. KRAS, BRAF and PIK3CA mutations are commonly found in colon cancers. In this study, we aimed to determine the mutation frequencies of KRAS, BRAF and PIK3CA and to establish whether such mutations may be used as prognostic and/or predictive factors in rectal cancer patients. We retrospectively reviewed the clinical and biological data of 98 consecutive operated patients between May 2006 and September 2009. We focused in patients who received surgery in our center after radiochemotherapy and in which tumor samples were available. In the 98 patients with a rectal cancer, the median follow-up time was 28.3 months (4–74). Eight out of ninety-eight patients experienced a local recurrence (8%) and 17/98 developed distant metastasis (17%). KRAS, BRAF and PIK3CA were identified respectively in 23 (23.5%), 2 (2%) and 4 (4%) patients. As described in previous studies, mutations in KRAS and BRAF were mutually exclusive. No patient with local recurrence exhibited KRAS or PIK3CA mutation and one harbored BRAF mutation (12.5%). Of the seventeen patients with distant metastasis (17%), 5 were presenting KRAS mutation (29%), one BRAF (5%) and one PIK3CA mutation (5%). No relationship was seen between PIK3CA, KRAS or BRAF mutation and local or distant recurrences. The frequencies of KRAS, BRAF and PIK3CA mutations in our study were lower than the average frequencies reported in colorectal cancers and no significant correlation was found between local/distant recurrences and KRAS, BRAF or PIK3CA mutations. Future studies with greater number of patients, longer follow-up time and greater power to predict associations are necessary to fully understand this relationship

  1. Ultrasensitive and selective gold film-based detection of mercury (II) in tap water using a laser scanning confocal imaging-surface plasmon resonance system in real time.

    Science.gov (United States)

    Zhang, Hongyan; Yang, Liquan; Zhou, Bingjiang; Liu, Weimin; Ge, Jiechao; Wu, Jiasheng; Wang, Ying; Wang, Pengfei

    2013-09-15

    An ultrasensitive and selective detection of mercury (II) was investigated using a laser scanning confocal imaging-surface plasmon resonance system (LSCI-SPR). The detection limit was as low as 0.01ng/ml for Hg(2+) ions in ultrapure and tap water based on a T-rich, single-stranded DNA (ssDNA)-modified gold film, which can be individually manipulated using specific T-Hg(2+)-T complex formation. The quenching intensity of the fluorescence images for rhodamine-labeled ssDNA fitted well with the changes in SPR. The changes varied with the Hg(2+) ion concentration, which is unaffected by the presence of other metal ions. The coefficients obtained for ultrapure and tap water were 0.99902 and 0.99512, respectively, for the linear part over a range of 0.01-100ng/ml. The results show that the double-effect sensor has potential for practical applications with ultra sensitivity and selectivity, especially in online or real-time monitoring of Hg(2+) ions pollution in tap water with the further improvement of portable LSCI-SPR instrument. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. The detectability of hepatic metastases in candidates of radiofrequency ablation: comparison for helical CT scanning and late-phase pulse-inversion harmonic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Won; Yoon, Kwon Ha; Kim, Eun A; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [School of Medicine, Wonkwang Univ., Iksan (Korea, Republic of)

    2002-02-01

    To compare dual-phase helical CT and pulse inversion harmonic US using microbubble contrast agents in the detection of hepatic metastases prior to radiofrequency (RF) ablation. Twenty-one patients in whom hepatic metastases from colorectal cancer had been diagnosed by dual-phase CT scanning and who were considered to be candidates for RF ablation underwent pulse-inversion barmonic US examination. Images were obtained 5 minutes after the bolus injection of microbubble contrast agent SH U 508 A (4.0 g, 300 mg/mL). The number of metastatic tumors revealed by CT and US was determined, and the findings were statistically analysed. The influence of the results of US examination on treatment planning was also evaluated. In 21 patients, 48 metastaic lesions were detected by helical CT, and 56 lesions by US. These eight additional lesions revealed by US occurred in six patients (29%), and their diameter was 3-13 (mean, 7.2) mm. In three of these patients, RF ablation could not be performed ,while in the other three, the additional lesions were ablated. Pulse-inversion harmonic US imaging using microbubble contrast agents may depict small hepatic metastatic tumors that were not apparent at CT. US-therefore appears to be useful in the planning of treatment prior to the RF ablation of hepatic metastases.

  3. In situ detection of the Zn(2+) release process of ZnO NPs in tumour cells by confocal laser scanning fluorescence microscopy.

    Science.gov (United States)

    Song, Wenshuang; Tang, Xiaoling; Li, Yong; Sun, Yang; Kong, Jilie; Qingguang, Ren

    2016-08-01

    The use of zinc oxide (ZnO) nanoparticles (NPs) for cancer is not yet clear for human clinical applications, which is primarily due to the lack of a better understanding of the action mechanisms and cellular consequences of the direct exposure of cells to these NPs. In this work, the authors have selected zinquin ethyl ester, a Zn(2+)-specific fluorescent molecular probe, to efficiently differentiate ZnO NPs and Zn(2+), and combined with confocal laser scanning microscopy (CLSM) to in situ study the Zn(2+) release process of ZnO NPs in cancer cell system through detecting the change of Zn(2+) level over time. During the experiments, the authors have designed the test group ZnO-2 in addition to assess the influence of a long-term storage on the characteristics of ZnO NPs in aqueous solution, and the Zn(2+) release process of ZnO NPs in cancer cell system. After three-month storage at room temperature, the release process became earlier and faster, which was consistent with previous results of transmission electron microscope, UV-Vis and PL spectra. It is a good detection method that combination of Zn(2+)-specific fluorescent molecular probe and CLSM, which will be helpful for ZnO NPs using in clinical research.

  4. Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells

    Science.gov (United States)

    Bennett Saidu, Nathaniel Edward; Bretagne, Marie; Mansuet, Audrey Lupo; Just, Pierre-Alexandre; Leroy, Karen; Cerles, Olivier; Chouzenoux, Sandrine; Nicco, Carole; Damotte, Diane; Alifano, Marco; Borghese, Bruno; Goldwasser, François; Batteux, Frédéric; Alexandre, Jérôme

    2018-01-01

    KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells. This effect was observed in patient-derived cancer cell lines harbouring a G12V KRAS mutation, compared with cell lines without such a mutation. In addition, KRAS*G12V over-expression in the human Caco-2 colon cancer cell line significantly promoted DMF-induced cell death, as well as DMF-induced- reactive oxygen species (ROS) formation and -glutathione (GSH) depletion. Moreover, in contrast to malignant cells, our data confirms that the same concentration of DMF has no significant cytotoxic effects on non-tumorigenic human ARPE-19 retinal epithelial, murine 3T3 fibroblasts and primary mice bone marrow cells; but is rather associated with NRF2 activation, decreased ROS and increased GSH levels. Furthermore, DJ-1 down-regulation experiments showed that this protein does not play a protective role against NRF2 in non-tumorigenic cells, as it does in malignant ones. This, interestingly, could be at the root of the differential effect of DMF observed between malignant and non-tumorigenic cells. Our results suggest for the first time that the dependence on NRF2 observed in mutated KRAS malignant cells makes them more sensitive to the cytotoxic effect of DMF, which thus opens up new prospects for the therapeutic applications of DMF. PMID:29507676

  5. Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells.

    Science.gov (United States)

    Bennett Saidu, Nathaniel Edward; Bretagne, Marie; Mansuet, Audrey Lupo; Just, Pierre-Alexandre; Leroy, Karen; Cerles, Olivier; Chouzenoux, Sandrine; Nicco, Carole; Damotte, Diane; Alifano, Marco; Borghese, Bruno; Goldwasser, François; Batteux, Frédéric; Alexandre, Jérôme

    2018-02-06

    KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells. This effect was observed in patient-derived cancer cell lines harbouring a G12V KRAS mutation, compared with cell lines without such a mutation. In addition, KRAS*G12V over-expression in the human Caco-2 colon cancer cell line significantly promoted DMF-induced cell death, as well as DMF-induced- reactive oxygen species (ROS) formation and -glutathione (GSH) depletion. Moreover, in contrast to malignant cells, our data confirms that the same concentration of DMF has no significant cytotoxic effects on non-tumorigenic human ARPE-19 retinal epithelial, murine 3T3 fibroblasts and primary mice bone marrow cells; but is rather associated with NRF2 activation, decreased ROS and increased GSH levels. Furthermore, DJ-1 down-regulation experiments showed that this protein does not play a protective role against NRF2 in non-tumorigenic cells, as it does in malignant ones. This, interestingly, could be at the root of the differential effect of DMF observed between malignant and non-tumorigenic cells. Our results suggest for the first time that the dependence on NRF2 observed in mutated KRAS malignant cells makes them more sensitive to the cytotoxic effect of DMF, which thus opens up new prospects for the therapeutic applications of DMF.

  6. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

    Directory of Open Access Journals (Sweden)

    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  7. 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.

  8. Comparison of 99mTc-MIBI scanning and sentinel node biopsy in the detection of occult melanoma lymph node metastases

    International Nuclear Information System (INIS)

    Alonso, O.; Lago, G.; Lopes de Amorim, M.C.; Juri, C.; Larre Borges, A.; Martinez, M.; De Boni, D.; Espasandin, J.; Priario, J.

    2002-01-01

    Aim: Sentinel node biopsy (SNB) is a highly accurate technique for detecting occult metastatic disease in the regional lymph nodes. Our group has reported that 99m Tc-MIBI scintigraphy is an imaging technique that can detect clinically undetectable metastases. This prospective study shows preliminary results on the comparison of both techniques for the detection of lymph node invasion. Material and Methods: Twenty-two consecutive patients (15 women, 7 men; mean age, 55 years) with primary melanoma > 1.0 mm thick were enrolled (mean 2.6 mm). Patients underwent 99m Tc-MIBI scintigraphy of regional lymph nodes 1-2 weeks before surgery, acquiring 10-minute planar images with a LFOV gamma camera. A preoperative lymphoscintigraphy using 99m Tc-colloidal (Re) sulphide was performed the day before surgery, using a dose of 74-93 MBq. Radio guided SNB was performed with a hand-held gamma probe. Lymph nodes were examined histologically and immunostained for S-100 and HMB-45. Results: The sentinel node (SN) was identified in 21/22 patients. An average of 1.6 SN/lesion were harvested from melanomas located in the following regions: head and neck (n=3), trunk (n=6), extremities (n=12). All patients with negative SN (n=11) were also negative with MIBI. In 10 cases the SN demonstrated metastatic involvement, whereas 99m Tc-MIBI was positive in 8 of them (80%). In cases with positive SN/negative 99m Tc-MIBI, the pathology report revealed micro metastatic disease. Conclusion: These preliminary results suggest that 99m Tc-MIBI scanning has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy

  9. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Directory of Open Access Journals (Sweden)

    Nibedita Chattopadhyay

    Full Text Available In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  10. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Science.gov (United States)

    Chattopadhyay, Nibedita; Berger, Allison J; Koenig, Erik; Bannerman, Bret; Garnsey, James; Bernard, Hugues; Hales, Paul; Maldonado Lopez, Angel; Yang, Yu; Donelan, Jill; Jordan, Kristen; Tirrell, Stephen; Stringer, Bradley; Xia, Cindy; Hather, Greg; Galvin, Katherine; Manfredi, Mark; Rhodes, Nelson; Amidon, Ben

    2015-01-01

    In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  11. Electrical impedance scanning as a new imaging modality in breast cancer detection - a short review of clinical value on breast application, limitations and perspectives

    International Nuclear Information System (INIS)

    Malich, A.; Boehm, T.; Facius, M.; Kleinteich, I.; Fleck, M.; Sauner, D.; Anderson, R.; Kaiser, W.A.

    2003-01-01

    Objective. Cancer cells exhibit altered local dielectric properties compared to normal cells, measurable as different electrical conductance and capacitance using electrical impedance scanning (EIS). Therefore, active biocompatible current is applied to the patient for calculation of both parameters taking into account frequency, voltage and current flow. Subjects and methods. 240 women with 280 sonographically and/or mammographically suspicious findings were examined using EIS. All lesions were histologically proven. A lesion was scored as positive, when a focal increased conductance and/or capacitance was measurable using EIS. The lesion was visible as a bright area in a 256 grey-scale computer output. Due to system limitations patients having a pacemaker or pregnant had to be excluded from the study. Results. 91/113 malignant and 108/167 benign lesions were correctly identified using EIS (80.5% sensitivity, 64.7% specificity). NPV and PPV of 83.1% and 60.7% were observed, respectively. Accuracy was 0.73. A wide range of factors can induce false positive results, although by an experienced observer a number of these findings can be detected such as scars, skin alterations, contact artefacts, air bubbles and naevi, hairs and interfering bone. Based upon visibility on ultrasound (194 lesions visible, 86 not visible) significant differences in the detection rate occurred. Histology-dependent detectability rate varied significantly with lowest rate in CIS-cases (50%). Specificity values varied histology-depending, too; probably depending on the rate of proliferation between 75% (inflammatory lesions) and papillomata (50%). Best detectability was observed in malignant lesions with a size between 20 and 30 mm. Further possible applications will be discussed regarding the currently available literature (lymph nodes, salivary glands, mathematical and animal based models). Conclusion. EIS appears to be a promising new additional technology providing a rather high

  12. EGFR and KRAS quality assurance schemes in pathology : generating normative data for molecular predictive marker analysis in targeted therapy

    NARCIS (Netherlands)

    Thunnissen, Erik; Bovée, Judith V M G; Bruinsma, Hans; van den Brule, Adriaan J C; Dinjens, Winand; Heideman, Daniëlle A M; Meulemans, Els; Nederlof, Petra; van Noesel, Carel; Prinsen, Clemens F M; Scheidel, Karen; van de Ven, Peter M; de Weger, Roel; Schuuring, Ed; Ligtenberg, Marjolijn

    2011-01-01

    Introduction The aim of this study was to compare the reproducibility of epidermal growth factor receptor (EGFR) immunohistochemistry (IHC), EGFR gene amplification analysis, and EGFR and KRAS mutation analysis among different laboratories performing routine diagnostic analyses in pathology in The

  13. Orthogonal identification of gunshot residue with complementary detection principles of voltammetry, scanning electron microscopy, and energy-dispersive X-ray spectroscopy: sample, screen, and confirm.

    Science.gov (United States)

    O'Mahony, Aoife M; Samek, Izabela A; Sattayasamitsathit, Sirilak; Wang, Joseph

    2014-08-19

    Field-deployable voltammetric screening coupled with complementary laboratory-based analysis to confirm the presence of gunshot residue (GSR) from the hands of a subject who has handled, loaded, or discharged a firearm is described. This protocol implements the orthogonal identification of the presence of GSR utilizing square-wave stripping voltammetry (SWSV) as a rapid screening tool along with scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to confirm the presence of the characteristic morphology and metal composition of GSR particles. This is achieved through the judicious modification of the working electrode of a carbon screen-printed electrode (CSPE) with carbon tape (used in SEM analysis) to fix and retain a sample. A comparison between a subject who has handled and loaded a firearm and a subject who has had no contact with GSR shows the significant variations in voltammetric signals and the presence or absence of GSR-consistent particles and constituent metals. This initial electrochemical screening has no effect on the integrity of the metallic particles, and SEM/EDX analysis conducted prior to and postvoltammetry show no differences in analytical output. The carbon tape is instrumental in retaining the GSR sample after electrochemical analysis, supported by comparison with orthogonal detection at a bare CSPE. This protocol shows great promise as a two-tier detection system for the presence of GSR from the hands of a subject, whereby initial screening can be conducted rapidly onsite by minimally trained operators; confirmation can follow at the same substrate to substantiate the voltammetric results.

  14. Selective detection of Fe2+ by combination of CePO4:Tb3+ nanocrystal-H2O2 hybrid system with synchronous fluorescence scan technique.

    Science.gov (United States)

    Chen, Hongqi; Ren, Jicun

    2012-04-21

    A new method for quenching kinetic discrimination of Fe(2+) and Fe(3+), and sensitive detection of trace amount of Fe(2+) was developed by using synchronous fluorescence scan technique. The principle of this assay is based on the quenching kinetic discrimination of Fe(2+) and Fe(3+) in CePO(4):Tb(3+) nanocrytals-H(2)O(2) hybrid system and the Fenton reaction between Fe(2+) and H(2)O(2). Stable, water-soluble and well-dispersible CePO(4):Tb(3+) nanocrystals were synthesized in aqueous solutions, and characterized by transmission electron microscopy (TEM) and electron diffraction spectroscopy (EDS). We found that both Fe(2+) and Fe(3+) could quench the synchronous fluorescence of CePO(4):Tb(3+) nanocrytals-H(2)O(2) system, but their quenching kinetics velocities were quite different. In the presence of Fe(3+), the synchronous fluorescent intensity was unchanged after only one minute, but in the presence of Fe(2+), the synchronous fluorescent intensity decreased slowly until 28 min later. The Fenton reaction between Fe(2+) and H(2)O(2) resulted in hydroxyl radicals which effectively quenched the synchronous fluorescence of the CePO(4):Tb(3+) nanocrystals due to the oxidation of Ce(3+) into Ce(4+) by hydroxyl radicals. Under optimum conditions, the linear range for Fe(2+) is 3 nM-2 μM, and the limit of detection is 2.0 nM. The method was used to analyze water samples.

  15. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    Science.gov (United States)

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  16. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

    Science.gov (United States)

    Voruganti, V Saroja; Göring, Harald H H; Diego, Vincent P; Cai, Guowen; Mehta, Nitesh R; Haack, Karin; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2007-10-01

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

  17. A simple method for detection of gunshot residue particles from hands, hair, face, and clothing using scanning electron microscopy/wavelength dispersive X-ray (SEM/WDX).

    Science.gov (United States)

    Kage, S; Kudo, K; Kaizoji, A; Ryumoto, J; Ikeda, H; Ikeda, N

    2001-07-01

    We devised a simple and rapid method for detection of gunshot residue (GSR) particles, using scanning electron microscopy/wavelength dispersive X-ray (SEM/WDX) analysis. Experiments were done on samples containing GSR particles obtained from hands, hair, face, and clothing, using double-sided adhesive coated aluminum stubs (tape-lift method). SEM/WDX analyses for GSR were carried out in three steps: the first step was map analysis for barium (Ba) to search for GSR particles from lead styphnate primed ammunition, or tin (Sn) to search for GSR particles from mercury fulminate primed ammunition. The second step was determination of the location of GSR particles by X-ray imaging of Ba or Sn at a magnification of x 1000-2000 in the SEM, using data of map analysis, and the third step was identification of GSR particles, using WDX spectrometers. Analysis of samples from each primer of a stub took about 3 h. Practical applications were shown for utility of this method.

  18. Safety and efficacy of the addition of simvastatin to panitumumab in previously treated KRAS mutant metastatic colorectal cancer patients.

    Science.gov (United States)

    Baas, Jara M; Krens, Lisanne L; Bos, Monique M; Portielje, Johanneke E A; Batman, Erdogan; van Wezel, Tom; Morreau, Hans; Guchelaar, Henk-Jan; Gelderblom, Hans

    2015-09-01

    Panitumumab has proven efficacy in patients with metastatic or locally advanced colorectal cancer patients, provided that they have no activating KRAS mutation in their tumour. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification of KRAS. We hypothesize that the activity of the RAS-induced pathway in patients with a KRAS mutation might be inhibited by simvastatin. This would theoretically result in increased sensitivity to panitumumab, potentially comparable with tumours with wild-type KRAS. A Simon two-stage design single-arm, phase II study was designed to test the safety and efficacy of the addition of simvastatin to panitumumab in colorectal cancer patients with a KRAS mutation after failing fluoropyrimidine-based, oxaliplatin-based and irinotecan-based therapy. The primary endpoint of this study was the proportion of patients alive and free from progression 11 weeks after the first administration of panitumumab, aiming for at least 40%, which is comparable with, although slightly lower than, that in KRAS wild-type patients in this setting. If this 40% was reached, then the study would continue into the second step up to 46 patients. Explorative correlative analysis for mutations in the KRAS and related pathways was carried out. One of 14 patients was free from progression at the primary endpoint time. The median progression-free survival was 8.4 weeks and the median overall survival status was 19.6 weeks. We conclude that the concept of mutant KRAS phenotype expression modulation with simvastatin was not applicable in the clinic.

  19. Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer

    DEFF Research Database (Denmark)

    Jensen, L H; Lindebjerg, J; Ploen, J

    2012-01-01

    BACKGROUND: Combination chemotherapy has proven beneficial in biliary tract cancer and further improvements may be achieved by individualizing treatment based on biomarkers and by adding biological agents. We report the effect of chemotherapy with panitumumab as first-line therapy for KRAS wild....... Combination chemotherapy with panitumumab in patients with KRAS wild-type tumors met the efficacy criteria for future testing in a randomized trial....

  20. KRAS early testing: consensus initiative and cost-effectiveness evaluation for metastatic colorectal patients in an Italian setting.

    Directory of Open Access Journals (Sweden)

    Carlo Barone

    Full Text Available KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC. Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert's board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY gained. In extensive sensitivity analyses ICER's were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of

  1. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

    International Nuclear Information System (INIS)

    Popovici, Vlad; Budinska, Eva; Bosman, Fred T; Tejpar, Sabine; Roth, Arnaud D; Delorenzi, Mauro

    2013-01-01

    The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in

  2. 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.

  3. 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.

  4. Tumour gene expression predicts response to cetuximab in patients with KRAS wild-type metas