Thu, 07 Aug 2008 21:36:55 BST CiteULike: Tag amplification http://www.citeulike.org/tag/amplification CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/weezerific/article/2547482 <i>Journal of Neuroscience Methods, Vol. 135, No. 1-2. (30 May 2004), pp. 67-70.</i><br /><br />Triple immunofluorescence method with two mouse monoclonal antibodies and another rabbit polyclonal antibody was established with catalyzed reporter deposition (CARD) amplification on thick floating sections from the rat cerebellum. One of the monoclonal antibodies (anti-calbindin), diluted maximally, probed with anti-mouse IgG-horseradish peroxidase (HRP) and amplified with Cy5-conjugated tyramide, immunolabeled cerebellar Purkinje cells and their arborization. Subsequently, a rabbit polyclonal IgG (anti-glial fibrillary acidic protein (anti-GFAP)), probed with anti-rabbit IgG-HRP, amplified with biotin-tyramide and visualized with fluorescein-isothiocyanate (FITC)-streptavidin, immunolabeled Bergmann's glia. Another mouse monoclonal IgG (anti-SNAP25), probed with anti-mouse IgG-rhodamine without CARD amplification, selectively visualized synaptic sites, because the maximal dilution of the other monoclonal antibody (anti-calbindin) was below the detection threshold of this anti-mouse IgG-rhodamine. Separation of the two signals (calbindin and SNAP25), each detected through mouse monoclonal antibody, was then based on the difference of sensitivity either with or without CARD amplification. Triple immunofluorescence is possible when just one of the three primary antibodies is from different species. Intensification of two of the three signals provides further advantages to examine immunolocalization of multiple epitopes on histological sections. Dual enhancement of triple immunofluorescence using two antibodies from the same species Ayako Nakamura Toshiki Uchihara doi:10.1016/j.jneumeth.2003.12.003 Journal of Neuroscience Methods, Vol. 135, No. 1-2. (30 May 2004), pp. 67-70. 2008-03-17T18:58:37-00:00 2004 Journal of Neuroscience Methods 135 1-2 67 70 amplification fluorescence immunofluorescence http://www.citeulike.org/user/vrich/article/2470170 <i>J Biochem Biophys Methods (23 December 2007)</i><br /><br />The recent advent of microarray technology and RNA amplification allows us to compare the expression profiles of thousands of genes from small amounts of tissue or cells. We have compared and contrasted various methods of RNA preparation, RNA amplification, target labelling and array analysis in order to achieve a streamlined protocol for microarraying small samples. We have concluded that usage of the NIA 15K cDNA array set, in combination with RNA extraction using the Mini RNA Isolation kit (Zymo), amplification with the RiboAmp kit (Arcturus), followed by indirect labelling via the Atlastrade mark PowerScripttrade mark Fluorescent Labelling kit (using a modified protocol), is optimal with a material derived from either very early stage mouse embryos or individually picked embryonic stem cell colonies. Normalisation using the analysis package Limma (Bioconductor) with data normalisation by print tip Loess, using the "normexp" function with an offset of 50 for background adjustment, and incorporating A-quantile between array normalisation was best with our results. Furthermore, RT-PCR confirmation of array results is achievable without amplification, thereby controlling for amplification bias. These methods will be of great utility in mapping the transcriptome of embryonic and other small samples. Optimization of minuscule samples for use with cDNA microarrays. Susan McLean Hunter Fiona C Mansergh Martin J Evans doi:10.1016/j.jprot.2007.11.011 J Biochem Biophys Methods (23 December 2007) 2008-03-05T06:57:57-00:00 2007 J Biochem Biophys Methods 0165-022X amplification arrays rna http://www.citeulike.org/user/voldog/article/813163 <i>Int J Radiat Oncol Biol Phys, Vol. 63, No. 3. (1 November 2005), pp. 695-703.</i><br /><br />PURPOSE: There have been conflicting reports in the literature regarding the prognostic significance of epidermal growth factor receptor (EGFR) amplification in patients with glioblastoma multiforme (GBM). The purpose of this study is to determine the prognostic significance of EGFR amplification in patients with GBM treated at the Cleveland Clinic Foundation. METHODS AND MATERIALS: A retrospective review of GBM patients treated with surgery at the Cleveland Clinic Foundation was performed. Amplification of EGFR was evaluated with fluorescence in situ hybridization in a total of 107 patients diagnosed between December 1995 and May 2003. In addition to EGFR status, various prognostic factors were evaluated to determine the factors that influenced survival and radiographic response rate. The median follow-up was 9 months. RESULTS: The overall median survival was 9.8 months, with a 1-year survival of 40%. Of the 107 patients in whom EGFR status was evaluated, 36 (33.6%) were found to have EGFR amplification. On multivariate analysis, median survival was found to be significantly improved for patients with age < 60 (12.6 months vs. 8 months, p = 0.0061), patients with Karnofsky Performance Status > or = 70 (12.1 months vs. 4.4 months, p < 0.0001), patients who had undergone subtotal resection or gross total resection (11.1 months vs. 4.1 months, p = 0.002), and patients who received a radiation dose > or = 60 Gy compared with no radiation (12.7 months vs. 3 months, p < 0.0001). There was no association of EGFR amplification with survival. When stratified by age (< 60 vs. > or = 60), EGFR status still did not reach statistical significance in predicting for survival. For the 81 patients who had radiographic follow-up, the 1-year overall local control was 14%. On univariate analysis, only treatment with radiation (< 60 Gy vs. > or = 60 Gy vs. no radiation, p = 0.03) was found to predict for improved local control. Treatment with radiation did not remain statistically significant on multivariate analysis. CONCLUSION: Epidermal growth factor receptor amplification was not found to be a significant prognostic indicator of overall survival or radiographic local control in patients with GBM treated with surgery at the Cleveland Clinic Foundation. Further studies are needed to fully delineate the significance of this molecular marker in patients with GBM. Epidermal growth factor receptor amplification does not have prognostic significance in patients with glioblastoma multiforme. AL Quan GH Barnett SY Lee MA Vogelbaum SA Toms SM Staugaitis RA Prayson DM Peereboom GH Stevens BH Cohen JH Suh doi:10.1016/j.ijrobp.2005.03.051 Int J Radiat Oncol Biol Phys, Vol. 63, No. 3. (1 November 2005), pp. 695-703. 2006-08-23T01:05:04-00:00 2005 Int J Radiat Oncol Biol Phys 0360-3016 63 3 695 703 amplification egfr gbm marker prognostic http://www.citeulike.org/user/stajich/article/3063776 <i>Nucleic acids research, Vol. 36, No. 13. (August 2008)</i><br /><br />Large-scale copy number variants (CNVs) have recently been recognized to play a role in human genome variation and disease. Approaches for analysis of CNVs in small samples such as microdissected tissues can be confounded by limited amounts of material. To facilitate analyses of such samples, whole genome amplification (WGA) techniques were developed. In this study, we explored the impact of Phi29 multiple-strand displacement amplification on detection of CNVs using oligonucleotide arrays. We extracted DNA from fresh frozen lymph node samples and used this for amplification and analysis on the Affymetrix Mapping 500k SNP array platform. We demonstrated that the WGA procedure introduces hundreds of potentially confounding CNV artifacts that can obscure detection of bona fide variants. Our analysis indicates that many artifacts are reproducible, and may correlate with proximity to chromosome ends and GC content. Pair-wise comparison of amplified products considerably reduced the number of apparent artifacts and partially restored the ability to detect real CNVs. Our results suggest WGA material may be appropriate for copy number analysis when amplified samples are compared to similarly amplified samples and that only the CNVs with the greatest significance values detected by such comparisons are likely to be representative of the unamplified samples. Impact of whole genome amplification on analysis of copy number variants. TJ Pugh AD Delaney N Farnoud S Flibotte M Griffith HI Li H Qian P Farinha RD Gascoyne MA Marra Nucleic acids research, Vol. 36, No. 13. (August 2008) 2008-07-30T16:48:28-00:00 2008 Nucleic acids research 1362-4962 36 13 amplification copy_number_variation genome http://www.citeulike.org/user/shearstj/article/1631706 <i>Genomics, Vol. 88, No. 1. (July 2006), pp. 111-121.</i><br /><br />We have developed a total RNA amplification and labeling strategy for use with Affymetrix GeneChips. Our protocol, which we denote BIIB, employs two rounds of linear T7 amplification followed by Klenow labeling to generate a biotinylated cDNA. In benchmarking studies using a titration of mouse universal total RNA, BIIB outperformed commercially available kits in terms of sensitivity, accuracy, and amplified target length, while providing equivalent results for technical reproducibility. BIIB maintained 50 and 44% present calls from 100 and 50 pg of total RNA, respectively. Inter- and intrasample precision studies indicated that BIIB produces an unbiased and complete expression profile within a range of 5 ng to 50 pg of starting total RNA. From a panel of spiked exogenous transcripts, we established the BIIB linear detection limit to be 20 absolute copies. Additionally, we demonstrate that BIIB is sensitive enough to detect the stochastic events inherent in a highly diluted sample. Using RNA isolated from whole tissues, we further validated BIIB accuracy and precision by comparison of 224 expression ratios generated by quantitative real-time PCR. The utility of our method is ultimately illustrated by the detection of biologically expected trends in a T cell/B cell titration of 100 primary cells flow sorted from a healthy mouse spleen. Accurate and precise transcriptional profiles from 50 pg of total RNA or 100 flow-sorted primary lymphocytes. JR Shearstone NE Allaire J Campos-Rivera S Rao S Perrin doi:10.1016/j.ygeno.2006.03.004 Genomics, Vol. 88, No. 1. (July 2006), pp. 111-121. 2007-09-07T14:09:55-00:00 2006 Genomics 0888-7543 88 1 111 121 amplification expression genechip microarray profiling transcriptional http://www.citeulike.org/user/shearstj/article/1631702 <i>J Biol Chem, Vol. 274, No. 15. (9 April 1999), pp. 9937-9945.</i><br /><br />Escherichia coli IbpB was overexpressed in a strain carrying a deletion in the chromosomal ibp operon and purified by refolding. Under our experimental conditions, IbpB exhibited pronounced size heterogeneity. Basic oligomers, roughly spherical and approximately 15 nm in diameter, interacted to form larger particles in the 100-200-nm range, which themselves associated to yield loose aggregates of micrometer size. IbpB suppressed the thermal aggregation of model proteins in a concentration-dependent manner, and its CD spectrum was consistent with a mostly beta-pleated secondary structure. Incubation at high temperatures led to a partial loss of secondary structure, the progressive exposure of tryptophan residues to the solvent, the dissociation of high molecular mass aggregates into approximately 600-kDa oligomers, and an increase in surface hydrophobicity. Structural changes were reversible between 37 and 55 degrees C, and, up to 55 degrees C, hydrophobic sites were reburied upon cooling. IbpB exhibited a biphasic unfolding trend upon guanidine hydrochloride (GdnHCl) treatment and underwent comparable conformational changes upon melting and during the first GdnHCl-induced transition. However, hydrophobicity decreased with increasing GdnHCl concentrations, suggesting that efficient exposure of structured hydrophobic sites involves denaturant-sensitive structural features. By contrast, IbpB hydrophobicity rose at high NaCl concentrations and increased further at high temperatures. Our results support a model in which temperature-driven conformational changes lead to the reversible exposure of normally shielded binding sites for nonnative proteins and suggest that both hydrophobicity and charge context may determine substrate binding to IbpB. Biochemical characterization of the small heat shock protein IbpB from Escherichia coli. JR Shearstone F Baneyx J Biol Chem, Vol. 274, No. 15. (9 April 1999), pp. 9937-9945. 2007-09-07T14:08:38-00:00 1999 J Biol Chem 0021-9258 274 15 9937 9945 amplification expression genechip microarray profiling transcriptional http://www.citeulike.org/user/sebastien_vigneau/article/1452152 <i>Proc Natl Acad Sci U S A (5 July 2007)</i><br /><br />Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect two-component regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification. A connector of two-component regulatory systems promotes signal amplification and persistence of expression. Akinori Kato Alexander Y Mitrophanov Eduardo A Groisman doi:10.1073/pnas.0704462104 Proc Natl Acad Sci U S A (5 July 2007) 2007-07-12T13:49:43-00:00 2007 Proc Natl Acad Sci U S A 0027-8424 amplification network persistence http://www.citeulike.org/user/sansamcl/article/420368 <i>Cancer Res, Vol. 58, No. 16. (15 August 1998), pp. 3677-3683.</i><br /><br />Amplification is a key mechanism whereby a cancer cell increases the message level of genes that confer a selective advantage when they are overexpressed. In breast cancer, there are many chromosome regions present in multiple copies relative to overall DNA copy number (amplicons), and their target genes are unknown. Using differential display, we have cloned and sequenced the full coding region of a candidate amplicon target gene located on chromosome 13. This candidate is the human homologue of the Caenorhabditis elegans cul-4 gene, cul-4A, a member of the novel cullin gene family, which is involved in cell cycle control of C. elegans. cul-4A was amplified and overexpressed in 3 of 14 breast cancer cell lines analyzed, and it was overexpressed in 8 additional cell lines in which it was not amplified. The latter observation, indicating that its overexpression can occur by mechanisms other than gene amplification, suggests that cul-4A plays a key role in carcinogenesis. Moreover, cul-4A was found to be amplified in 17 of 105 (16%) cases of untreated primary breast cancers, and 14 of 30 cases analyzed (47%) were shown by RNA in situ hybridization to overexpress cul-4A. These results suggest that up-regulation of cul-4A may play an important role in tumor progression. The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. LC Chen S Manjeshwar Y Lu D Moore BM Ljung WL Kuo SH Dairkee M Wernick C Collins HS Smith Cancer Res, Vol. 58, No. 16. (15 August 1998), pp. 3677-3683. 2005-12-02T20:37:26-00:00 1998 Cancer Res 0008-5472 58 16 3677 3683 amplification cul4a http://www.citeulike.org/user/sansamcl/article/420362 <i>Hepatology, Vol. 35, No. 6. (June 2002), pp. 1476-1484.</i><br /><br />We carried out molecular cytogenetic characterization of 11 cell lines derived from hepatocellular carcinomas (HCCs) and 51 primary HCCs. Comparative genomic hybridization (CGH) revealed frequent amplification at 13q34, where we had detected amplification in several other types of tumor, including esophageal squamous cell carcinomas (ESC). Previously, we suggested possible involvement of TFDP1, encoding a transcription factor DP-1, in the 13q34 amplification observed in a primary ESC. Therefore, we investigated amplifications and expression levels of 5 genes mapped on the amplified region, including TFDP1, for exploring amplification targets at 13q34 in HCCs. 3 of those genes, TFDP1, CUL4A (cullin 4A), and CDC16 (cell division cycle 16), showed distinct amplification and consequent over-expression in some cell lines. Moreover, each was amplified in 3 or 4 of the 51 primary HCCs, and all 3 were amplified in 2 tumors, in which their expression patterns correlated with amplification patterns. To elucidate the functional role of TFDP1 in HCC, we examined expression levels of genes downstream of TFDP1 with real-time quantitative polymerase chain reaction (PCR). Expression of cyclin E gene (CCNE1) correlated closely with that of TFDP1 in not only cell lines, but also primary tumors. Treatment of HCC cells with the antisense oligonucleotide targeting TFDP1 resulted in down-regulation of CCNE1, suggesting that TFDP1 overexpression led to up-regulation of CCNE1 that encoded a positive regulator for cell cycle G1/S transition. In conclusion, our findings suggest that TFDP1, CUL4A, and CDC16 are probable targets of an amplification mechanism and therefore may be involved, together or separately, in development and/or progression of some HCCs. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. K Yasui S Arii C Zhao I Imoto M Ueda H Nagai M Emi J Inazawa doi:10.1053/jhep.2002.33683 Hepatology, Vol. 35, No. 6. (June 2002), pp. 1476-1484. 2005-12-02T20:33:23-00:00 2002 Hepatology 0270-9139 35 6 1476 1484 amplification cul4a http://www.citeulike.org/user/rodney/article/1537500 <i>J. Mater. Chem., Vol. 13, No. 11. (2003), pp. 2796-2808.</i><br /><br />A new soluble conjugated metalloporphyrin polymer has been synthesised as its complex with zinc(II), lead(II) and copper(II) and as the free-base. The zinc complex aggregates in non-coordinating solvents, due to coordination of the amide side-chains to the zinc centres. These aggregates dissociate on addition of pyridine to give single-strand complexes; the dissociation process displays an amazingly high positive cooperativity (Hill coefficient: n H = 3.2 at 50% sat., rising to 11.5 at 95% sat.). The zinc polymer binds 4,4?-bipyridyl to form a double-strand ladder complex; this self-assembly process holds neighbouring porphyrins coplanar and increases the ?-conjugation, resulting in a red-shift in the electronic absorption. Degenerate four wave mixing, at 1064 nm, was used to characterise the optical nonlinearity of these polymers. Both the real and imaginary parts of the third-order susceptibility ?(3) are strongly amplified in the lead(II) complex and in the double-strand assembly. We estimate that the two-photon absorption cross-section of the ladder complex is 5 x 104 GM per macrocycle at 1064 nm, which is an order of magnitude higher than the highest values reported for other chromophores, suggesting that these polymers may be relevant to a variety of applications including photodynamic therapy. Two methods for amplifying the optical nonlinearity of a conjugated porphyrin polymer: Transmetallation and self-assembly TEO Screen JRG Thorne RG Denning DG Bucknall HL Anderson J. Mater. Chem., Vol. 13, No. 11. (2003), pp. 2796-2808. 2007-08-06T05:06:29-00:00 2003 J. Mater. Chem. 13 11 2796 2808 amplification nonlinear optical porphyrin self-assembly transmetallation http://www.citeulike.org/user/rlmcinnes/article/471869 <i>Genomics (31 October 2005)</i><br /><br />The ability to utilize formalin-fixed, paraffin-embedded (FFPE) archival specimens reliably for high-resolution molecular genetic analysis would be of immense practical application in the study of human disease. We have evaluated the ability of the GenomePlex whole genome amplification (WGA) kit to amplify frozen and FFPE tissue for use in array CGH (aCGH). GenomePlex gave highly representative data compared with unamplified controls both from frozen material (Pearson's R(2) = 0.898) and from FFPE (R(2) = 0.883). Artifactual amplification observed using DOP-PCR at chromosomes 1p, 3, 13q, and 16p was not seen with GenomePlex. Highly reproducible aCGH profiles were obtained using as little as 5 ng starting material from FFPE (R(2) = 0.918). This WGA method should readily lend itself to the determination of DNA copy number alterations from small fresh-frozen and FFPE clinical tumor specimens, although some care must be taken to optimize the DNA extraction procedure. Array CGH using whole genome amplification of fresh-frozen and formalin-fixed, paraffin-embedded tumor DNA. Suzanne E Little Raisa Vuononvirta Jorge S Reis-Filho Rachael Natrajan Marjan Iravani Kerry Fenwick Alan Mackay Alan Ashworth Kathy Pritchard-Jones Chris Jones doi:10.1016/j.ygeno.2005.09.019 Genomics (31 October 2005) 2006-01-20T02:27:32-00:00 2005 Genomics 0888-7543 amplification cgh embedded ffpe fixed formalin microarray paraffin http://www.citeulike.org/user/pjasper/article/1284017 <i>Eur J Cancer, Vol. 43, No. 4. (March 2007), pp. 725-735.</i><br /><br />AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials. Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). R Giuliani V Durbecq A Di Leo M Paesmans D Larsimont JY Leroy M Borms A Vindevoghel G Jerusalem V D'Hondt L Dirix JL Canon V Richard V Cocquyt F Majois M Reginster J Demol JP Kains P Delree C Keppens C Sotiriou MJ Piccart F Cardoso doi:10.1016/j.ejca.2006.11.019 Eur J Cancer, Vol. 43, No. 4. (March 2007), pp. 725-735. 2007-05-08T17:19:32-00:00 2007 Eur J Cancer 0959-8049 43 4 725 735 activation amplification breast erbb2 herceptin http://www.citeulike.org/user/pjasper/article/1234847 <i>J Clin Oncol, Vol. 23, No. 31. (1 November 2005), pp. 8081-8092.</i><br /><br />PURPOSE: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib. PATIENTS AND METHODS: We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. RESULTS: EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. CONCLUSION: EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. DW Bell TJ Lynch SM Haserlat PL Harris RA Okimoto BW Brannigan DC Sgroi B Muir MJ Riemenschneider RB Iacona AD Krebs DH Johnson G Giaccone RS Herbst C Manegold M Fukuoka MG Kris J Baselga JS Ochs DA Haber doi:10.1200/JCO.2005.02.7078 J Clin Oncol, Vol. 23, No. 31. (1 November 2005), pp. 8081-8092. 2007-04-18T20:08:09-00:00 2005 J Clin Oncol 0732-183X 23 31 8081 8092 amplification iressa mutation nsclc http://www.citeulike.org/user/pjasper/article/397238 <i>British Journal of Cancer, Vol. aop, No. current. (15 November 2005)</i> HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients F Cappuzzo L Toschi I Domenichini S Bartolini GL Ceresoli E Rossi V Ludovini A Cancellieri E Magrini L Bemis WA Franklin L Crino PA Bunn FR Hirsch M Varella-Garcia doi:10.1038/sj.bjc.6602865 British Journal of Cancer, Vol. aop, No. current. (15 November 2005) 2005-11-16T17:25:29-00:00 2005 British Journal of Cancer 0007-0920 aop current Nature Publishing Group amplification erbb3 iressa nsclc http://www.citeulike.org/user/pjasper/article/1234822 <i>J Clin Oncol, Vol. 23, No. 22. (1 August 2005), pp. 5007-5018.</i><br /><br />PURPOSE: In non-small-cell lung cancer (NSCLC), response to tyrosine kinase inhibitors (TKIs) is significantly associated with the presence of increased copy number and/or activating mutations of the epidermal growth factor receptor gene (EGFR). Preclinical data indicate that HER2, a member of the EGFR family, could enhance TKI sensitivity. PATIENTS AND METHODS: HER2 gene copy numbers per cell were evaluated by fluorescent in situ hybridization (FISH) in 102 NSCLC patients treated with gefitinib, and previously evaluated for EGFR status by FISH, immunohistochemistry, and presence of mutations. RESULTS: Patients with HER2 high copy number (high polysomy and gene amplification [HER2 FISH positive]) represented 22.8% of patients, and compared with patients with no or low gain (HER2 FISH negative), had significantly better objective response (OR, 34.8% v 6.4%; P = .001), disease control rate (DCR, 56.5% v 33.3%; P = .04), time to progression (TTP, 9.05 v 2.7 months; P = .02), and a trend toward longer overall survival (OS, 20.8 v 8.4 months; P = .056). HER2 protein expression investigated by immunohistochemistry was positive in only five of 72 (7%) patients analyzed and all 89 patients tested by DNA sequencing were negative for mutations in HER2 exon 20. Patients with HER2 FISH-positive tumors displaying increased expression of EGFR protein, gene gain, or mutations (EGFR positive) had a significantly better OR, DCR, TTP, and OS than patients negative for both receptors. CONCLUSION: Increased copy number of the HER2 gene is associated with gefitinib sensitivity in EGFR-positive patients, supporting use of HER2 FISH analysis for selection of patients for TKI therapy. Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. F Cappuzzo M Varella-Garcia H Shigematsu I Domenichini S Bartolini GL Ceresoli E Rossi V Ludovini V Gregorc L Toschi WA Franklin L Crino AF Gazdar PA Bunn FR Hirsch doi:10.1200/JCO.2005.09.111 J Clin Oncol, Vol. 23, No. 22. (1 August 2005), pp. 5007-5018. 2007-04-18T19:38:10-00:00 2005 J Clin Oncol 0732-183X 23 22 5007 5018 amplification erbb2 iressa nsclc http://www.citeulike.org/user/pjasper/article/1284065 <i>Ann Oncol, Vol. 18, No. 4. (April 2007), pp. 752-760.</i><br /><br />BACKGROUND: Biological markers for optimal selection of patient to epidermal growth factor receptor (EGFR)-targeted therapies are not established in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: EGFR/HER2 gene copy number by FISH, EGFR protein and pAKT expression by immunohistochemistry (IHC) and EGFR and KRAS mutations were tested in 204 gefitinib-treated NSCLC patients. RESULTS: Increased EGFR and HER2 gene copy number (FISH+), EGFR protein overexpression (IHC+), EGFR mutations and pAKT overexpression were all associated with significantly higher response rates (33%, 29%, 22%, 39% and 20% respectively). EGFR FISH+ (32%) and IHC+ (61%) correlated with improved survival, while EGFR mutations (27%), KRAS mutations (26%) and pAKT expression (69%) did not. In multivariate survival analysis EGFR FISH and IHC were independent predictive markers. EGFR FISH+/IHC+ patients (23%) had a median survival of 21 months versus 6 months for double-negative patients (30%). CONCLUSION: Combination of EGFR FISH and IHC is effective predictor for benefit from gefitinib. Patients with double-negative results are unlikely to benefit in western NSCLC populations. Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. F Hirsch M Varella-Garcia F Cappuzzo J McCoy L Bemis A Xavier R Dziadziuszko P Gumerlock K Chansky H West A Gazdar L Crino D Gandara W Franklin P Bunn Ann Oncol, Vol. 18, No. 4. (April 2007), pp. 752-760. 2007-05-08T17:46:41-00:00 2007 Ann Oncol 0923-7534 18 4 752 760 amplification egfr inhibitor iressa nsclc http://www.citeulike.org/user/nikko/article/2908481 <i>Risk Analysis, Vol. 13, No. 6. (1993), pp. 611-623.</i><br /><br />A comprehensive approach to managing risk must draw on both the descriptive insights of the behavioral sciences and the prescriptive clarity of the management sciences. On the descriptive side, this study develops structural models to explain how the impact upon society of an accident or other unfortunate event is influenced by the physical consequences of the event, perceived risk, media coverage, and public response. Our findings indicate that the media and public response play crucial roles in determining the impact of an unfortunate event. Public response appears to be determined by perceptions that the event was caused by managerial incompetence and is a signal of future risk. On the prescriptive side, we briefly discuss how these findings based upon structural models can be incorporated into a decision-analytic procedure known as an influence diagram. Incorporating structural models into research on the social amplification of risk: implications for theory construction and decision making William Burns Paul Slovic Roger Kasperson Jeanne Kasperson Ortwin Renn Srinivas Emani doi:10.1111/j.1539-6924.1993.tb01323.x Risk Analysis, Vol. 13, No. 6. (1993), pp. 611-623. 2008-06-19T19:27:22-00:00 1993 Risk Analysis 13 6 611 623 amplification consequence construction coverage decision future impact making media model perception physical public research response risk social societal structural theory http://www.citeulike.org/user/nikko/article/2869086 <i>(10 July 2003)</i><br /><br />Edited by three well-known analysts of risk and its communication, this volume brings together contributions from a group of international experts in risk perception and risk communication. Key conceptual issues are discussed as well as a range of recent case studies that span BSE and food safety, AIDS/HIV, nuclear power, child protection, Y2K, electromagnetic fields, and waste incineration. The volume also draws attention to issues in public policy, risk management and risk communication practice. The Social Amplification of Risk (10 July 2003) 2008-06-06T10:55:02-00:00 2003 Cambridge University Press amplification risk social http://www.citeulike.org/user/nikko/article/2658488 <i>Risk Analysis, Vol. 8, No. 2. (1988), pp. 177-187.</i><br /><br />One of the most perplexing problems in risk analysis is why some relatively minor risks or risk events, as assessed by technical experts, often elicit strong public concerns and result in substantial impacts upon society and economy. This article sets forth a conceptual framework that seeks to link systematically the technical assessment of risk with psychological, sociological, and cultural perspectives of risk perception and risk-related behavior. The main thesis is that hazards interact with psychological, social, institutional, and cultural processes in ways that may amplify or attenuate public responses to the risk or risk event. A structural description of the social amplification of risk is now possible. Amplification occurs at two stages: in the transfer of information about the risk, and in the response mechanisms of society. Signals about risk are processed by individual and social amplification stations, including the scientist who communicates the risk assessment, the news media, cultural groups, interpersonal networks, and others. Key steps of amplifications can be identified at each stage. The amplified risk leads to behavioral responses, which, in turn, result in secondary impacts. Models are presented that portray the elements and linkages in the proposed conceptual framework. The social amplification of risk: a conceptual framework Roger Kasperson Ortwin Renn Paul Slovic Halina Brown Jacque Emel Robert Goble Jeanne Kasperson Samuel Ratick doi:10.1111/j.1539-6924.1988.tb01168.x Risk Analysis, Vol. 8, No. 2. (1988), pp. 177-187. 2008-04-11T17:56:23-00:00 1988 Risk Analysis 8 2 177 187 amplification framework mtr perception risk social http://www.citeulike.org/user/nikko/article/2679274 <i>Risk Analysis, Vol. 8, No. 2. (1988), pp. 193-197.</i> Should Social Amplification of Risk Be Counteracted? Arie Rip doi:10.1111/j.1539-6924.1988.tb01170.x Risk Analysis, Vol. 8, No. 2. (1988), pp. 193-197. 2008-04-17T00:59:54-00:00 1988 Risk Analysis 8 2 193 197 amplification mtr perception risk social http://www.citeulike.org/user/nikko/article/2773546 <i>The International Journal of Press/Politics, Vol. 11, No. 3. (1 July 2006), pp. 67-88.</i><br /><br />This article uses a qualitative case study approach to examine policy-oriented risk communication in the battle between Greenpeace and Shell over the disposal of the Brent Spar oil structure. Policy-agenda-setting literature is fused with literature from the social amplification of risk framework (SARF) and transnational advocacy networks to generate further insights. This analysis demonstrates that in attempting to influence policy, Greenpeace and Shell are prepared to redefine risk according to their own strategic needs and arenas of operation. It suggests that media exposure impacts policy both by shaping public perception of risk (rather than of policy) and by shaping policy makers' perception of public opinion. It is suggested that for successful policy-oriented risk communication, social trust in the communicator must be cultivated and maintained with key audiences prior to, and during, risk communication 10.1177/1081180X06289213 Policy agenda setting and risk communication: Greenpeace, Shell, and issues of trust Vian Bakir doi:10.1177/1081180X06289213 The International Journal of Press/Politics, Vol. 11, No. 3. (1 July 2006), pp. 67-88. 2008-05-08T20:38:01-00:00 2006 The International Journal of Press/Politics 11 3 67 88 advocacy agenda amplification brent communication framework greenpeace networks oil policy risk sarf setting shell social spar transnational trust http://www.citeulike.org/user/nigini/article/2136589 <i>(3 Dec 1997)</i><br /><br />A quantum computer has a clear advantage over a classical computer for exhaustive search. The quantum mechanical algorithm for exhaustive search was originally derived by using subtle properties of a particular quantum mechanical operation called the Walsh-Hadamard (W-H) transform. This paper shows that this algorithm can be implemented by replacing the W-H transform by almost any quantum mechanical operation. This leads to several new applications where it improves the number of steps by a square-root. It also broadens the scope for implementation since it demonstrates quantum mechanical algorithms that can readily adapt to available technology. Quantum computers can search rapidly by using almost any transformation Lov Grover (3 Dec 1997) 2007-12-17T13:58:37-00:00 1997 algorithms amplification amplitude quantum http://www.citeulike.org/user/nigini/article/759408 <i>(15 May 2000)</i><br /><br />Consider a Boolean function $χ: X \to {0,1}$ that partitions set $X$ between its good and bad elements, where $x$ is good if $χ(x)=1$ and bad otherwise. Consider also a quantum algorithm $\mathcal A$ such that $A \ket0 = ∑_x∈ X α_x \ketx$ is a quantum superposition of the elements of $X$, and let $a$ denote the probability that a good element is produced if $A \ket0$ is measured. If we repeat the process of running $A$, measuring the output, and using $χ$ to check the validity of the result, we shall expect to repeat $1/a$ times on the average before a solution is found. *Amplitude amplification* is a process that allows to find a good $x$ after an expected number of applications of $A$ and its inverse which is proportional to $1/\sqrta$, assuming algorithm $A$ makes no measurements. This is a generalization of Grover's searching algorithm in which $A$ was restricted to producing an equal superposition of all members of $X$ and we had a promise that a single $x$ existed such that $χ(x)=1$. Our algorithm works whether or not the value of $a$ is known ahead of time. In case the value of $a$ is known, we can find a good $x$ after a number of applications of $A$ and its inverse which is proportional to $1/\sqrta$ even in the worst case. We show that this quadratic speedup can also be obtained for a large family of search problems for which good classical heuristics exist. Finally, as our main result, we combine ideas from Grover's and Shor's quantum algorithms to perform amplitude estimation, a process that allows to estimate the value of $a$. We apply amplitude estimation to the problem of *approximate counting*, in which we wish to estimate the number of $x∈ X$ such that $χ(x)=1$. We obtain optimal quantum algorithms in a variety of settings. Quantum Amplitude Amplification and Estimation Gilles Brassard Peter Hoyer Michele Mosca Alain Tapp (15 May 2000) 2006-07-14T18:22:08-00:00 2000 algorithms amplification amplitude quantum http://www.citeulike.org/user/miguel/article/320309 <i>Nat Biotechnol, Vol. 20, No. 9. (September 2002), pp. 940-943.</i><br /><br />Analysis of transcript representation on gene microarrays requires microgram amounts of total RNA or DNA. Without amplification, such amounts are obtainable only from millions of cells. However, it may be desirable to determine transcript representation in few or even single cells in aspiration biopsies, rare population subsets isolated by cell sorting or laser capture, or micromanipulated single cells. Nucleic-acid amplification methods could be used in these cases, but it is difficult to amplify different transcripts in a sample without distorting quantitative relationships between them. Linear isothermal RNA amplification has been used to amplify as little as 10 ng of total cellular RNA, corresponding to the amount obtainable from thousands of cells, while still preserving the original abundance relationships. However, the available procedures require multiple steps, are labor intensive and time consuming, and have not been shown to preserve abundance information from smaller starting amounts. Exponential amplification, on the other hand, is a relatively simple technology, but is generally considered to bias abundance relationships unacceptably. These constraints have placed beyond current reach the secure and routine application of microarray analysis to single or small numbers of cells. Here we describe results obtained with a rapid and highly optimized global reverse transcription#150;PCR (RT-PCR) procedure. Contrary to prevalent expectations, the exponential approach preserves abundance relationships through amplification as high as 3 x 10(11)-fold. Further, it reduces by a million-fold the input amount of RNA needed for microarray analysis, and yields reproducible results from the picogram range of total RNA obtainable from single cells. Representation is faithfully preserved in global cDNA amplified exponentially from sub-picogram quantities of mRNA. NN Iscove M Barbara M Gu M Gibson C Modi N Winegarden doi:10.1038/nbt729 Nat Biotechnol, Vol. 20, No. 9. (September 2002), pp. 940-943. 2005-09-15T03:40:53-00:00 2002 Nat Biotechnol 1087-0156 20 9 940 943 amplification mrna http://www.citeulike.org/user/miguel/article/321116 <i>Blood, Vol. 97, No. 8. (15 April 2001), pp. 2257-2268.</i><br /><br />Although hematopoiesis is known to proceed from stem cells through a graded series of multipotent, oligopotent, and unipotent precursor cells, it has been difficult to resolve these cells physically one from another. There is, therefore, corresponding uncertainty about the exact distribution and timing of the expression of genes known to be important in hematopoietic differentiation. In earlier work, the generation of a set of amplified complementary DNAs (cDNAs) from single precursor cells was described, whose biologic potential was determined by the outcome of cultured sibling cells. In this study, the new acquisition of cDNA from multipotent myeloid precursor cells is described, as is the mapping of RNA-level expression of 17 distinct cytokine receptors (c-kit, Flk-1, Flk-2/Flt-3, c-fms, gp130, erythropoietin receptor, GM-CSFRalpha, G-CSFR, TNFR1, IL-1RI, IL-1RII, IL-2Rbeta, IL-3-specific beta receptor, IL-4R, IL-6Ralpha, IL-7Ralpha, and IL-11Ralpha) to the enlarged sample set, spanning stages from pentapotent precursors through oligopotent intermediates to committed and maturing cells in the myeloid and lymphoid lineages. Although the enhanced scope and resolving power of the analysis yielded previously unreported observations, there was overall agreement with known biologic responsiveness at individual stages, and major contradictions did not arise. Moreover, each precursor category displayed a unique overall pattern of hybridization to the matrix of 17 receptor probes, supporting the notion that each sample pool indeed reflected a unique precursor stage. Collectively, the results provide supportive evidence for the validity of the cDNA assignments to particular stages, the depth of the information captured, and the unique capacity of the sample matrix to resolve individual stages in the hematopoietic hierarchy. Resolution of pluripotential intermediates in murine hematopoietic differentiation by global complementary DNA amplification from single cells: confirmation of assignments by expression profiling of cytokine receptor transcripts. F Billia M Barbara J McEwen M Trevisan NN Iscove Blood, Vol. 97, No. 8. (15 April 2001), pp. 2257-2268. 2005-09-15T13:37:06-00:00 2001 Blood 0006-4971 97 8 2257 2268 amplification cdna cells stem http://www.citeulike.org/user/michaelbussmann/article/2443899 <i>(19 April 2006)</i><br /><br />Written from an industrial perspective, Solid-State Laser Engineering discusses in detail the characteristics, design, construction, and performance of solid-state lasers. Emphasis is placed on engineering and practical considerations; phenomenological aspects using models are preferred to abstract mathematical derivations. Since its first edition almost 30 years ago this book has become the standard in the field of solid-state lasers for scientists,engineers and graduate students.</P> <P>This new edition has been extensively revised and updated to account for recent developments in the areas of diode-laser pumping, laser materials and nonlinear crystals. Completely new sections have been added dealing with frequency control, the theory of mode-locking, femto second lasers, high efficiency harmonic generation, passive and acousto-optic Q-switching, semiconductor saturable absorber mirrors (SESAM) and peridically poled nonlinear crystals. Solid-State Laser Engineering (Springer Series in Optical Sciences) Walter Koechner (19 April 2006) 2008-02-28T15:09:55-00:00 2006 Springer amplification chirp cpa damage diode laser mode-locking nonlinear optical oscillator pulse pumping q-switch resonator self-focusing solid-state thermo-optic http://www.citeulike.org/user/michaelbussmann/article/2889834 <i>Physical Review Letters, Vol. 81, No. 22. (30 November 1998), 4879.</i><br /><br />An initially short ( <1/ωp) laser pulse can be superradiantly amplified by a counterpropagating long low-intensity pump while remaining ultrashort. This superradiant amplification occurs if the frequency of the pulse is lower than that of the pump, and the initial pulse intensity is sufficiently high. Numerical simulations indicate that the short pulse can be amplified to an intensity hundreds of times the pump intensity, with the pump depletion as high as 40%. This implies that the long pump is efficiently time compressed without frequency chirping and pulse stretching, making the superradiant amplification an interesting alternative to chirped-pulse amplification. Superradiant Amplification of an Ultrashort Laser Pulse in a Plasma by a Counterpropagating Pump G Shvets NJ Fisch A Pukhov J Meyer-Ter-Vehn doi:10.1103/PhysRevLett.81.4879 Physical Review Letters, Vol. 81, No. 22. (30 November 1998), 4879. 2008-06-12T18:03:13-00:00 1998 Physical Review Letters 81 22 4879 American Physical Society amplification counterpropagating laser pulse superradiant ultrashort http://www.citeulike.org/user/michaelbussmann/article/2478294 <i>Physical Review Letters, Vol. 100, No. 9. (2008)</i><br /><br />We produce a 600-ns pulse of 1.86-dB squeezed vacuum at 795 nm in an optical parametric amplifier and store it in a rubidium vapor cell for 1 µs using electromagnetically induced transparency. The recovered pulse, analyzed using time-domain homodyne tomography, exhibits up to 0.21±0.04 dB of squeezing. We identify the factors leading to the degradation of squeezing and investigate the phase evolution of the atomic coherence during the storage interval. Quantum Memory for Squeezed Light Jürgen Appel Eden Figueroa Dmitry Korystov M Lobino AI Lvovsky doi:10.1103/PhysRevLett.100.093602 Physical Review Letters, Vol. 100, No. 9. (2008) 2008-03-06T11:04:03-00:00 2008 Physical Review Letters 100 9 APS amplification eit electromagnetically homodyne induced light optical parametric rubidium squeezed storage tomography transparency vapour http://www.citeulike.org/user/michaelbussmann/article/2889660 <i>Physics of Fluids B: Plasma Physics, Vol. 4, No. 7. (1992), pp. 2315-2325.</i><br /><br />The development of compact high-intensity lasers, made possible by the technique of chirped pulse amplification, is reviewed. This includes the complexities of high-power laser implementation, such as the generation of short pulses, pulse cleaning, wide-bandwidth amplification, temporal stretching and compression, and the requirements for high-average powers. Details of specific solid-state laser systems are given. Some applications of these lasers to short-pulse coherent short-wavelength [x-ray ultraviolet (XUV)] sources are also reviewed. This includes several nonlinear effects observed by focusing a subpicosecond laser into a gas; namely, an anomalous scaling of harmonic generation in atomic media, an upper limit on the conversion efficiency of relativistic harmonics in a plasma, and the observation of short-pulse self-focusing and multifoci formation. Finally, the effects of large ponderomotive pressures (100 Mbars) in short-pulse high-intensity laser–plasma interactions are discussed, with relevance both to recombination x-ray lasers and a novel method of igniting thermonuclear fusion. Development and applications of compact high-intensity lasers G Mourou D Umstadter doi:10.1063/1.860202 Physics of Fluids B: Plasma Physics, Vol. 4, No. 7. (1992), pp. 2315-2325. 2008-06-12T16:37:43-00:00 1992 Physics of Fluids B: Plasma Physics 4 7 2315 2325 AIP amplification chirp cpa high-intensity laser pulse http://www.citeulike.org/user/michaelbussmann/article/2864393 <i>Physics of Plasmas, Vol. 10, No. 12. (2003), pp. 4848-4855.</i><br /><br />View This Record in Scopus Particle-in-cell simulations of Raman laser amplification in preformed plasmas Daniel Clark Nathaniel Fisch Physics of Plasmas, Vol. 10, No. 12. (2003), pp. 4848-4855. 2008-06-05T11:10:34-00:00 2003 Physics of Plasmas 10 12 4848 4855 AIP algorithm amplification laser particle-in-cell pic raman scattering simulation http://www.citeulike.org/user/michaelbussmann/article/3040237 <i>Appl. Opt., Vol. 42, No. 34. (1 December 2003), pp. 6934-6938.</i><br /><br />We report on highly efficient transmission gratings in fused silica with a grating period of 800 nm generated by electron-beam lithography. At a wavelength of 1060 nm, 95% diffraction efficiency is achieved under Littrow conditions. The damage threshold, extremely enhanced compared with conventional gold-coated diffraction gratings, makes these gratings the key elements in high average power ( > 100 W) femtosecond fiber chirped-pulse amplification systems. Highly Efficient Transmission Gratings in Fused Silica for Chirped-Pulse Amplification Systems Tina Clausnitzer Jens Limpert Karsten Zöllner Holger Zellmer Hans-Joerg Fuchs Ernst-Bernhard Kley Andreas Tünnermann Marco Jupé Detlev Ristau Appl. Opt., Vol. 42, No. 34. (1 December 2003), pp. 6934-6938. 2008-07-24T15:33:19-00:00 2003 Appl. Opt. 42 34 6934 6938 OSA amplification chirped cpa fused grating pulse silica transmission http://www.citeulike.org/user/masaakif/article/2370120 <i>IEEE Transactions on Information Theory, Vol. 54, No. 2. (February 2008), pp. 680-691.</i><br /><br />We consider distillation of secret bits from partially secret noisy correlations <emphasis><formula formulatype="inline"><tex>$P_rm ABE$</tex> </formula></emphasis>, shared between two honest parties and an eavesdropper. The most studied distillation scenario consists of joint operations on a large number of copies of the distribution <emphasis><formula formulatype="inline"> <tex>$(P_rm ABE)^N$</tex></formula></emphasis>, assisted with public communication. Here we consider distillation with only one copy of the distribution, and instead of rates, the &#x201C;quality&#x201D; of the distilled secret bits is optimized, where the &#x201C;quality&#x201D; is quantified by the secret-bit fraction of the result. The secret-bit fraction of a binary distribution is the proportion which constitutes a secret bit between Alice and Bob. With local operations and public communication the maximal extractable secret-bit fraction from a distribution <emphasis><formula formulatype="inline"><tex>$P_rm ABE$</tex></formula></emphasis> is found, and is denoted by <emphasis><formula formulatype="inline"><tex>$Lambda[P_rm ABE]$</tex></formula></emphasis>. This quantity is shown to be nonincreasing under local operations and public communication, and nondecreasing under eavesdropper's local operations: <emphasis><formula formulatype="inline"><tex>$Lambda$</tex></formula></emphasis> is a secrecy monotone. It is shown that if <emphasis><formula formulatype="inline"><tex>$Lambda[P_rm ABE]> 1/2$</tex></formula></emphasis> then <emphasis><formula formulatype="inline"> <tex>$P_rm ABE$</tex></formula></emphasis> is distillable, thus providing a sufficient condition for distillability. A simple expression for <emphasis><formula formulatype="inline"><tex>$Lambda[P_rm ABE]$</tex></formula></emphasis> is found when the eavesdropper is decoupled, and when the honest parties' information is binary and the local operations are reversible. Intriguingly, for general di- stributions the (optimal) operation requires local degradation of the data. Key Distillation and the Secret-Bit Fraction Nick Jones Lluís Masanes doi:10.1109/TIT.2007.913264 IEEE Transactions on Information Theory, Vol. 54, No. 2. (February 2008), pp. 680-691. 2008-02-13T15:40:31-00:00 2008 IEEE Transactions on Information Theory 54 2 680 691 agreement amplification cryptography information privacy quantum secret-key theory http://www.citeulike.org/user/jmeppley/article/3014382 <i>Science, Vol. 321, No. 5886. (11 July 2008), pp. 211-212.</i><br /><br />10.1126/science.1161890 PALEONTOLOGY: New Tricks with Old Bones Rachel Mackelprang Edward Rubin doi:10.1126/science.1161890 Science, Vol. 321, No. 5886. (11 July 2008), pp. 211-212. 2008-07-17T13:52:50-00:00 2008 Science 321 5886 211 212 amplification genomics http://www.citeulike.org/user/jackjackjjj/article/1284193 <i>Science (26 April 2007)</i><br /><br />The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are used clinically for the treatment of lung cancers with EGFR activating mutations, but the tumors invariably develop drug resistance. To investigate resistance mechanisms, we isolated gefitinib-resistant clones from an EGFR mutant lung cancer cell line. The resistant cells displayed amplification of the MET oncogene and maintained activation of ERBB3/PI3K/Akt signaling in the presence of gefitinib. Inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 out of 18 (22%) lung cancer specimens that had become resistant to gefitinib or erlotinib. Because amplified MET activates the ERBB3/PI3K pathway in other tumor cell lines, our results raise the possibility that MET amplification promotes drug resistance in other ERBB-driven cancers. MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling. Jeffrey A Engelman Kreshnik Zejnullahu Tetsuya Mitsudomi Youngchul Song Courtney Hyland Joon Oh Park Neal Lindeman Christopher-Michael Gale Xiaojun Zhao James Christensen Takayuki Kosaka Alison J Holmes Andrew M Rogers Federico Cappuzzo Tony Mok Charles Lee Bruce E Johnson Lewis C Cantley Pasi A Jänne doi:10.1126/science.1141478 Science (26 April 2007) 2007-05-08T20:02:16-00:00 2007 Science 1095-9203 amplification http://www.citeulike.org/user/jackjackjjj/article/903583 <i>Oncogene, Vol. 17, No. 18. (5 November 1998), pp. 2403-2411.</i><br /><br />We have previously documented that transgenic mice expressing SV40 Tag regulated by the rat prostatic steroid-binding protein C3(1) 5'-flanking region display multistage mammary tumorigenesis. To delineate genetic changes associated with mammary tumor progression, comparative genomic hybridization (CGH) was performed. CGH revealed a consistent gain of the telomeric region of chromosome 6. This region contains the Ki-ras proto-oncogene. Analyses of genomic DNA by Southern blot demonstrated up to 40-fold amplification of the Ki-ras gene. Ki-ras amplification was detected in 12, 46 and 68% of tumors from 4, 5 and 6 month old mice, respectively, whereas no amplifications were found in any preneoplastic mammary tissues. Tumors bearing Ki-ras gene amplification exhibited high levels of Ki-ras RNA and protein. The over-expressed Ki-Ras protein in these tumors appeared functionally active as indicated by the elevated MAP kinase activity. These data demonstrate that while Ki-ras amplification might not be an early event, there is a strong association between Ki-ras amplification and over-expression and mammary tumor progression in this model. This study also shows that CGH is a powerful and useful technique for identifying chromosomal copy number changes during tumor progression, and that this model may provide a predictable in vivo system for studying gene amplification. Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice. ML Liu FC Von Lintig M Liyanage MA Shibata CL Jorcyk T Ried GR Boss JE Green doi:10.1038/sj.onc.1202456 Oncogene, Vol. 17, No. 18. (5 November 1998), pp. 2403-2411. 2006-10-18T09:51:39-00:00 1998 Oncogene 0950-9232 17 18 2403 2411 amplification cgh genome k-ras mouse http://www.citeulike.org/user/jackjackjjj/article/1372765 <i>Biochimie, Vol. 68, No. 7-8. (g 1986), pp. 1019-1023.</i><br /><br />The structure of the ras gene family was analyzed in two human teratocarcinoma-derived cell lines, Tera I and Tera II, by DNA restriction enzyme digestion and Southern blot. We report here a ten-fold amplification of the c-Ki-ras-2 gene in these cell lines, whereas no structural alterations seem to occur either in c-Ha-ras-1 or N-ras. We also provide evidence indicating that no point mutation at codon 12, specifically recognized by Sac I, was detected. Moreover, DNA rearrangement, due to the loss of a Pvu II site located in the intervening sequences between the third and the fourth exon, has been found in both Tera I and Tera II. Amplification and rearrangement of Ki-ras oncogene in human teratocarcinoma-derived cell lines. J Tobaly-Tapiero F Saal J Peries R Emanoil-Ravier Biochimie, Vol. 68, No. 7-8. (g 1986), pp. 1019-1023. 2007-06-08T13:05:24-00:00 1986 Biochimie 0300-9084 68 7-8 1019 1023 amplification k-ras http://www.citeulike.org/user/jackjackjjj/article/1372760 <i>Anticancer Res, Vol. 14, No. 3A. (n 1994), pp. 921-926.</i><br /><br />Thirty one biopsy samples of fresh Kaposi's sarcoma (KS) skin lesions were examined for alteration of the K-ras oncogene by differential PCR, SSCP and nucleic acid sequencing. Three KS specimens showed amplification of K-ras and 7 were found to have various mutations at exon 1 of the K-ras gene. Eight of the 10 K-ras gene alterations detected were found in more advanced nodular stage KS lesions, while only 2 were observed in the plaque stage KS tumors. Activation of the K-ras oncogene may play a role in the malignant progression of this unusual neoplasm. Gene amplification and multiple mutations of the K-ras oncogene in Kaposi's sarcoma. A Nicolaides YQ Huang JJ Li WG Zhang AE Friedman-Kien Anticancer Res, Vol. 14, No. 3A. (n 1994), pp. 921-926. 2007-06-08T13:04:19-00:00 1994 Anticancer Res 0250-7005 14 3A 921 926 amplification k-ras http://www.citeulike.org/user/jackjackjjj/article/835479 <i>J Exp Clin Cancer Res, Vol. 25, No. 1. (March 2006), pp. 73-78.</i><br /><br />The ras gene family (H, K and N-ras) encodes the Ras protein, a GTPase-activating protein that regulates several signal transduction pathways including cellular proliferation and differentiation. Mutations in codons 12, 13 and 61 of the ras genes constitute one of the most frequent alterations in human cancer. In the Western Hemisphere, a low frequency of mutations in these genes has been observed in head and neck carcinomas; a higher frequency has been found in countries such as India and Taiwan. Increased protein expression is a relatively frequent event in larynx carcinomas. This study was aimed to evaluate the participation of the k-ras gene and Ras expression in 20 Mexican patients with larynx squamous carcinoma, 2 with dysplasia and 4 with normal mucosa. Samples (of 26 patients) were embedded in paraffin and immunohistochemical analysis was performed for the Ras protein, as well as amplification of the k-ras gene exon 1 (108 bp) by laser capture microdissection. Then, DNA extraction, PCR and sequencing were performed looking for possible mutation in codons 12 and 13. All patients with larynx carcinoma were men, median age 62 years. Eighty-five percent of the patients had risk factors such as smoking and/or alcohol consumption, 25% were in clinical stages I and II, and 75% in stages III and IV; 45% of the patients presented tumor recurrence or persistence. In this study, no mutations were found in codons 12 or 13 of the k-ras gene; however, protein expression was observed in 95% of the samples and a higher expression of the protein was associated with tumor recurrence or persistence, although this was not statistically significant. Unexpectedly, well-differentiated carcinomas and dysplasias presented an increase in protein expression. These results suggest that ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events. Mutational analysis of K-ras and Ras protein expression in larynx squamous cell carcinoma. LM Ruíz-Godoy R CM Garcia-Cuellar NE Herrera González BL Suchil E Pérez-Cárdenas Y Sácnchez-Pérez ML Suárez-Roa A Meneses J Exp Clin Cancer Res, Vol. 25, No. 1. (March 2006), pp. 73-78. 2006-09-08T13:56:36-00:00 2006 J Exp Clin Cancer Res 0392-9078 25 1 73 78 amplification k-ras http://www.citeulike.org/user/jackjackjjj/article/1372738 <i>Mol Carcinog, Vol. 14, No. 4. (December 1995), pp. 286-293.</i><br /><br />Mutated ras genes have been found to be conspicuously absent from primary tumors of the esophagus, although high expression of ras p21 oncoprotein in some esophageal squamous cell carcinomas and mutations of the Ki- and Ha-ras genes in esophageal carcinoma cell lines have been reported. In this study, we found amplification of the Ki-ras gene in four of 10 esophageal adenocarcinomas (40%). No such amplification was observed among 61 squamous cell carcinomas, one pseudosarcomatous carcinoma, and eight esophageal cell lines, nor in six adenocarcinomas of the stomach. In two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki-ras proteins when compared with normal samples. This Ki-ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with the survival of the patients, or with the presence of other genetic alterations. These findings provide the first evidence for amplification of the Ki-ras gene in human esophageal cancer, which is restricted to adenocarcinomas. We also found that six of eight adenocarcinomas had point mutations in the p53 gene; this is a considerably higher prevalence than that reported for esophageal squamous cell carcinomas. These results strongly suggest that esophageal adenocarcinomas differ from squamous cell carcinomas in their molecular genetic characteristics. High frequency of Ki-ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus. C Galiana JC Lozano B Bancel H Nakazawa H Yamasaki Mol Carcinog, Vol. 14, No. 4. (December 1995), pp. 286-293. 2007-06-08T13:02:57-00:00 1995 Mol Carcinog 0899-1987 14 4 286 293 amplification k-ras http://www.citeulike.org/user/jackjackjjj/article/1318518 <i>Nature (21 May 2007)</i> Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers Richard Maser Bhudipa Choudhury Peter Campbell Bin Feng Kwok-Kin Wong Alexei Protopopov Jennifer O’neil Alejandro Gutierrez Elena Ivanova Ilana Perna Eric Lin Vidya Mani Shan Jiang Kate Mcnamara Sara Zaghlul Sarah Edkins Claire Stevens Cameron Brennan Eric Martin Ruprecht Wiedemeyer Omar Kabbarah Cristina Nogueira Gavin Histen Jon Aster Marc Mansour Veronique Duke Letizia Foroni Adele Fielding Anthony Goldstone Jacob Rowe Yaoqi Wang Thomas Look Michael Stratton Lynda Chin Andrew Futreal Ronald Depinho doi:10.1038/nature05886 Nature (21 May 2007) 2007-05-22T03:41:01-00:00 2007 Nature 0028-0836 Nature Publishing Group amplification http://www.citeulike.org/user/jackjackjjj/article/1372564 <i>EMBO J, Vol. 3, No. 12. (1 December 1984), pp. 2943-2946.</i><br /><br />Amplifications of two oncogenes, c-K-ras-2 and c-myc, were found in a human lung giant cell carcinoma (LGCC) Lu-65, which is maintained in nude mice. The extent of c-K-ras-2 and myc amplifications were estimated to be 10- and 8-fold, respectively, by means of the Southern hybridization procedure. In addition, NIH3T3 cells were transformed by transfection of Lu-65 DNA and the transforming gene was identified as c-K-ras-2. c-K-ras-2 genes were cloned from a gene library of Lu-65 and a single point mutation causing a substitution of cysteine for glycine in codon 12 was found by DNA sequencing. It was concluded that the amplification of the c-myc and c-K-ras-2 genes are accompanied by point mutational activation of c-K-ras-2 in the human LGCC Lu-65. This is the first report of multiple gene amplification accompanied by a point mutation of oncogenes in human cancer cells, providing further support for the idea that co-operation of at least two activated cellular oncogenes is required for carcinogenesis. A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer. Y Taya K Hosogai S Hirohashi Y Shimosato R Tsuchiya N Tsuchida M Fushimi T Sekiya S Nishimura EMBO J, Vol. 3, No. 12. (1 December 1984), pp. 2943-2946. 2007-06-08T12:36:28-00:00 1984 EMBO J 0261-4189 3 12 2943 2946 amplification k-ras http://www.citeulike.org/user/jackjackjjj/article/1582069 <i>PLoS Biol, Vol. 2, No. 12. (December 2004)</i><br /><br />"Adaptive mutation" denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac(-)Escherichia coli cells on lactose medium induces Lac(+)revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele. A crucial distinction between alternative hypotheses for the mechanisms of adaptive mutation hinges on whether these amplification and frameshift mutation events are distinct, or whether amplification is a molecular intermediate, producing an intermediate cell type, in colonies on a pathway to frameshift mutation. The latter model allows the evolutionarily conservative idea of increased mutations (per cell) without increased mutation rate (by virtue of extra gene copies per cell), whereas the former requires an increase in mutation rate, potentially accelerating evolution. To resolve these models, we probed early events leading to rare adaptive mutations and report several results that show that amplification is not the precursor to frameshift mutation but rather is an independent adaptive outcome. (i) Using new high-resolution selection methods and stringent analysis of all cells in very young (micro)colonies (500-10,000 cells), we find that most mutant colonies contain no detectable lac-amplified cells, in contrast with previous reports. (ii) Analysis of nascent colonies, as young as the two-cell stage, revealed mutant Lac(+)cells with no lac-amplified cells present. (iii) Stringent colony-fate experiments show that microcolonies of lac-amplified cells grow to form visible colonies of lac-amplified, not mutant, cells. (iv) Mutant cells do not overgrow lac-amplified cells in microcolonies fast enough to mask the lac-amplified cells. (v)lac-amplified cells are not SOS-induced, as was proposed to explain elevated mutation in a sequential model. (vi) Amplification, and not frameshift mutation, requires DNA polymerase I, demonstrating that mutation is separable from amplification, and also illuminating the amplification mechanism. We conclude that amplification and mutation are independent outcomes of adaptive genetic change. We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression. Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms. PJ Hastings A Slack JF Petrosino SM Rosenberg doi:10.1371/journal.pbio.0020399 PLoS Biol, Vol. 2, No. 12. (December 2004) 2007-08-22T09:21:22-00:00 2004 PLoS Biol 1545-7885 2 12 amplification http://www.citeulike.org/user/jackjackjjj/article/882384 <i>PLoS Comput Biol, Vol. 1, No. 6. (November 2005)</i><br /><br />Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-of-heterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphism (SNP) array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a) determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site), and (b) infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation. An R software package containing the methods described in this paper is freely available at http://genome.dfci.harvard.edu/~tlaframb/PLASQ. Allele-specific amplification in cancer revealed by SNP array analysis. T LaFramboise BA Weir X Zhao R Beroukhim C Li D Harrington WR Sellers M Meyerson doi:10.1371/journal.pcbi.0010065 PLoS Comput Biol, Vol. 1, No. 6. (November 2005) 2006-10-03T06:20:29-00:00 2005 PLoS Comput Biol 1553-7358 1 6 allele amplification egfr mutation snps specific http://www.citeulike.org/user/jackjackjjj/article/882382 <i>N Engl J Med, Vol. 353, No. 19. (10 November 2005), pp. 2012-2024.</i><br /><br />BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown. METHODS: We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors. We determined the molecular correlates of clinical response, validated them in an independent data set, and identified effects of the molecular abnormalities in vitro. RESULTS: Of 49 patients with recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had tumor shrinkage of at least 25 percent. Pretreatment tissue was available for molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was significantly associated with a clinical response (P<0.001; odds ratio, 51; 95 percent confidence interval, 4 to 669). These findings were validated in 33 patients who received similar treatment for glioblastoma at a different institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468). In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib. CONCLUSIONS: Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. IK Mellinghoff MY Wang I Vivanco DA Haas-Kogan S Zhu EQ Dia KV Lu K Yoshimoto JH Huang DJ Chute BL Riggs S Horvath LM Liau WK Cavenee PN Rao R Beroukhim TC Peck JC Lee WR Sellers D Stokoe M Prados TF Cloughesy CL Sawyers PS Mischel doi:10.1056/NEJMoa051918 N Engl J Med, Vol. 353, No. 19. (10 November 2005), pp. 2012-2024. 2006-10-03T06:19:02-00:00 2005 N Engl J Med 1533-4406 353 19 2012 2024 amplification drug egfr mutation pten sensitivity http://www.citeulike.org/user/jackjackjjj/article/1582067 <i>Crit Rev Biochem Mol Biol, Vol. 42, No. 4. (g 2007), pp. 271-283.</i><br /><br />Modern techniques are revealing that repetition of segments of the genome, called amplification or gene amplification, is very common. Amplification is found in all domains of life, and occurs under conditions where enhanced expression of the amplified genes is advantageous. Amplification extends the range of gene expression beyond that which is achieved by control systems. It also is reversible because it is unstable, breaking down by homologous recombination. Amplification is believed to be the driving force in the clustering of related functions, in that it allows them to be amplified together. Amplification provides the extra copies of genes that allow evolution of functions to occur while retaining the original function. Amplification can be induced in response to cellular stressors. In many cases, it has been shown that the genomic regions that are amplified include those genes that are appropriate to upregulate for a specific stressor. There is some evidence that amplification occurs as part of a broad, general stress response, suggesting that organisms have the capacity to induce structural changes in the genome. This then allows adaptation to the stressful conditions. The mechanisms by which amplification arises are now being studied at the molecular level, but much is still unknown about the mechanisms in all organisms. Recent advances in our understanding of amplification in bacteria suggests new interpretations of events leading to human copy number variation, as well as evolution in general. Adaptive amplification. PJ Hastings doi:10.1080/10409230701507757 Crit Rev Biochem Mol Biol, Vol. 42, No. 4. (g 2007), pp. 271-283. 2007-08-22T09:20:52-00:00 2007 Crit Rev Biochem Mol Biol 1040-9238 42 4 271 283 amplification http://www.citeulike.org/user/jackjackjjj/article/882381 <i>Cancer Res, Vol. 65, No. 13. (1 July 2005), pp. 5561-5570.</i><br /><br />Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing approximately 115,000 single nucleotide polymorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the PTPRD locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. High-level amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified high-level amplification of EGFR in three NSCLC specimens, FGFR1 in two specimens and ERBB2 and MET in one specimen each. EGFR amplification was shown to be independent of kinase domain mutational status. Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis. X Zhao BA Weir T LaFramboise M Lin R Beroukhim L Garraway J Beheshti JC Lee K Naoki WG Richards D Sugarbaker F Chen MA Rubin PA Jänne L Girard J Minna D Christiani C Li WR Sellers M Meyerson doi:10.1158/0008-5472.CAN-04-4603 Cancer Res, Vol. 65, No. 13. (1 July 2005), pp. 5561-5570. 2006-10-03T06:17:35-00:00 2005 Cancer Res 0008-5472 65 13 5561 5570 amplification egfr mutation http://www.citeuli