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Sample records for erbb2 amplified advanced

  1. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

    Science.gov (United States)

    Burstein, Harold J; Sun, Yan; Dirix, Luc Y; Jiang, Zefei; Paridaens, Robert; Tan, Antoinette R; Awada, Ahmad; Ranade, Anantbhushan; Jiao, Shunchang; Schwartz, Gary; Abbas, Richat; Powell, Christine; Turnbull, Kathleen; Vermette, Jennifer; Zacharchuk, Charles; Badwe, Rajendra

    2010-03-10

    Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial. Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.

  2. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    Science.gov (United States)

    Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC

  3. Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer

    International Nuclear Information System (INIS)

    Contino, Flavia; Mazzarella, Claudia; Ferro, Arianna; Lo Presti, Mariavera; Roz, Elena; Lupo, Carmelo; Perconti, Giovanni; Giallongo, Agata; Feo, Salvatore

    2013-01-01

    The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide −514 and −262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC

  4. Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

    International Nuclear Information System (INIS)

    Andolfo, Immacolata; Orditura, Michele; Ciardiello, Fortunato; De Vita, Fernando; Zollo, Massimo; Petrosino, Giuseppe; Vecchione, Loredana; De Antonellis, Pasqualino; Capasso, Mario; Montanaro, Donatella; Gemei, Marica; Troncone, Giancarlo; Iolascon, Achille

    2011-01-01

    Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression. Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays. The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels. The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer

  5. The role of ERBB2 gene polymorphisms in leprosy susceptibility

    Directory of Open Access Journals (Sweden)

    Jamile Leão Rêgo

    2015-03-01

    Full Text Available Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05 in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus.

  6. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas.

    Science.gov (United States)

    Deniziaut, Gabrielle; Tille, Jean Christophe; Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-11-08

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening.

  7. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

    Energy Technology Data Exchange (ETDEWEB)

    Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J; Brugge, Joan S

    2001-08-08

    Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

  8. ERBB-2 overexpression as a risk factor for malignant phaeochromocytomas and paraganglinomas.

    Science.gov (United States)

    Wang, Weiqing; Zhong, Xu; Ye, Lei; Qi, Yan; Su, TingWei; Wei, Qing; Xie, Jing; Jiang, Lei; Jiang, Yiran; Zhou, Weiwei; Cui, Bin; Ning, Guang

    2016-06-01

    There are currently no good histological or molecular markers to differentiate benign from malignant phaeochromocytomas and paraganglinomas (PPGLs). Our previous cross-sectional study observed that ERBB-2 overexpression was associated with malignant PPGLs. This study aimed to evaluate the predictive value of ERBB-2 overexpression for metastasis in PPGLs in a large population. A total of 262 patients diagnosed as PPGLs in our institution between 2002 and 2012 were included. We analysed ERBB-2 protein expression in the primary PPGL tumours by immunohistochemistry (IHC) and ERBB-2 amplification by fluorescence in situ hybridization (FISH). Direct Sanger sequencing was performed to examine ERBB-2 exon 20 mutations. The occurrence of malignant PPGLs was documented in the follow-up period. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate the association between ERBB-2 overexpression and metastasis of PPGLs. Twenty-six (9·9%) patients had ERBB-2 overexpression in their primary PPGL tumours, which was significantly associated with ERBB-2 amplification (17/25, 68%). No ERBB-2 mutation was found. At a median follow-up of 4·5 years, a total of 23 malignant PPGLs were documented, including eight (30·8%) patients in the ERBB-2 overexpression group and 15 (6·4%) patients in the ERBB-2-negative group. The incidence rate of metastasis was 5·3 per 100 person-years vs 1·4 per 100 person-years in the ERBB-2 overexpression and ERBB-2-negative groups (P overexpression was associated with decreased metastasis-free survival (P = 0·001, log-rank test). After adjusting for primary tumour size and location, Cox regression analysis revealed that ERBB-2 overexpression was independently associated with risk of malignant PPGLs (HR = 2·78; 95% CI, 1·12-6·90; P = 0·028). Patients harbouring tumours with ERBB-2 overexpression have a significantly higher risk of developing malignant PPGLs. © 2016 John Wiley & Sons Ltd.

  9. Advances in high-power rf amplifiers

    International Nuclear Information System (INIS)

    Tallerico, P.J.

    1979-01-01

    Several powerful accelerators and storage rings are being considered that will require tens or even hundreds of megawatts of continuous rf power. The economics of such large machines can be dictated by the cost and efficiency of the rf amplifiers. The overall design and performance of such narrow-band amplifiers, operating in the 50- to 1500-MHz region, are being theoretically studied as a function of frequency to determine the optimum rf amplifier output power, gain, efficiency, and dc power requirements. The state of the art for three types of amplifiers (gridded tubes, klystrons, and gyrocons) is considered and the development work necessary to improve each is discussed. The gyrocon is a new device, hence its various embodiments are discussed in detail. The Soviet designs are reviewed and the gyrocon's strengths and weaknesses are compared to other types of microwave amplifiers. The primary advantages of the gyrocon are the very large amount of power available from a single device and the excellent efficiency and stable operation. The klystron however, has much greater gain and is simpler mechanically. At very low frequencies, the small size of the gridded tube makes it the optimum choice for all but the most powerful systems

  10. Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry

    International Nuclear Information System (INIS)

    Salido, Marta; Solé, Francesc; Tusquets, Ignasi; Corominas, Josep M; Suarez, Marta; Espinet, Blanca; Corzo, Cristina; Bellet, Meritxell; Fabregat, Xavier; Serrano, Sergi

    2005-01-01

    One of the most common genetic aberrations associated with breast cancer is the amplification and overexpression of the ERBB2 proto-oncogene located at chromosome 17, bands q12-21. The amplification/overexpression occurs in 25 to 30% of all breast cancers. In breast cancer, aneusomy of chromosome 17, either monosomy or polysomy, is frequently observed by conventional cytogenetics and fluorescence in situ hybridization (FISH). The aim of this study was to discover whether or not numerical aberrations on chromosome 17 have a correlation to the amplification or overexpression of the ERBB2 gene and to analyze their clinical implications in subgroups showing 2+ or 3+ positive scores by immunohistochemistry (IHC). We used FISH on a series of 175 formalin-fixed paraffin-embedded breast carcinomas to detect ERBB2 amplification, using a dual-probe system for the simultaneous enumeration of the ERBB2 gene and the centromeric region of chromosome 17, as well as using IHC to detect overexpression. We analyzed clinical and pathological variables in a subgroup of patients with 2+ and 3+ IHC scores (147 patients), to describe any differences in clinicopathological characteristics between polysomic and non-polysomic cases with the use of the χ 2 test. We found 13% of cases presenting polysomy, and three cases presented monosomy 17 (2%). According to the status of the ERBB2 gene, instances of polysomy 17 were more frequently observed in non-amplified cases than in FISH-amplified cases, suggesting that the mechanism for ERBB2 amplification is independent of polysomy 17. Polysomy 17 was detected in patients with 2+ and 3+ IHC scores. We found that nodal involvement was more frequent in polysomic than in non-polysomic cases (P = 0.046). The determination of the copy number of chromosome 17 should be incorporated into the assesment of ERBB2 status. It might also be helpful to differentiate a subgroup of breast cancer patients with polysomy of chromosome 17 and overexpression of ERBB2

  11. Common ERBB2 polymorphisms and risk of breast cancer in a white British population: a case–control study

    International Nuclear Information System (INIS)

    Benusiglio, Patrick R; Ponder, Bruce AJ; Lesueur, Fabienne; Luccarini, Craig; Conroy, Donald M; Shah, Mitul; Easton, Douglas F; Day, Nick E; Dunning, Alison M; Pharoah, Paul D

    2005-01-01

    About two-thirds of the excess familial risk associated with breast cancer is still unaccounted for and may be explained by multiple weakly predisposing alleles. A gene thought to be involved in low-level predisposition to the disease is ERBB2 (HER2). This gene is involved in cell division, differentiation, and apoptosis and is frequently amplified in breast tumours. Its amplification correlates with poor prognosis. Moreover, the coding polymorphism I655V has previously been associated with an increased risk of breast cancer. We aimed to determine if common polymorphisms (frequency ≥ 5%) in ERBB2 were associated with breast cancer risk in a white British population. Five single-nucleotide polymorphisms (SNPs) were selected for study: SNP 1 near the promoter, SNP 2 in intron 1, SNP 3 in intron 4, SNP 4 in exon 17 (I655V), and SNP 5 in exon 27 (A1170P). We tested their association with breast cancer in a large case–control study (n = 2192 cases and 2257 controls). There were no differences in genotype frequencies between cases and controls for any of the SNPs examined. To investigate the possibility that a common polymorphism not included in our study might be involved in breast cancer predisposition, we also constructed multilocus haplotypes. Our set of SNPs generated all existing (n = 6) common haplotypes and no differences were seen in haplotype frequencies between cases and controls (P = 0.44). In our population, common ERBB2 polymorphisms are not involved in predisposition to breast cancer

  12. Aberrations of ERBB2 and TOP2A Genes in Breast Cancer

    DEFF Research Database (Denmark)

    Nielsen, Kirsten Vang; Müller, Sven; Møller, Susanne

    2009-01-01

    genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase...... spreads from cell lines showed that simultaneous amplification is not a simple co-amplification of a whole amplicon containing both genes. Most gene signals are translocated to abnormal marker chromosomes. ERBB2 genes but not TOP2A genes are present in tandem amplicons, leading to a higher ERBB2 ratio....... This observation was confirmed by patient FISH data: among 276 (43% of all patients) abnormal tumors, 67% had different ERBB2 and TOP2A status. ERBB2 amplification with normal TOP2A status was found in 36% of the abnormal tumors (15% of all patients). Simultaneous amplification of both genes was found in 28...

  13. Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

    Energy Technology Data Exchange (ETDEWEB)

    Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: i.h.madshus@medisin.uio.no [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)

    2013-02-01

    The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

  14. Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

    International Nuclear Information System (INIS)

    Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke; Rødland, Marianne Skeie; Stang, Espen; Madshus, Inger Helene

    2013-01-01

    The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub 4 ) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub 4 chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub 4 was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub 4 was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub 4 was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

  15. Role of Erbin in ErbB2-dependent breast tumor growth

    Science.gov (United States)

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-01-01

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

  16. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    Science.gov (United States)

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

  17. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

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    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  18. A combination of Trastuzumab and 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation and cytotoxicity in ErbB2-overexpressing breast cancer cells.

    Science.gov (United States)

    Raja, Srikumar M; Clubb, Robert J; Bhattacharyya, Mitra; Dimri, Manjari; Cheng, Hao; Pan, Wei; Ortega-Cava, Cesar; Lakku-Reddi, Alagarsamy; Naramura, Mayumi; Band, Vimla; Band, Hamid

    2008-10-01

    ErbB2 (or Her2/Neu) overexpression in breast cancer signifies poorer prognosis, yet it has provided an avenue for targeted therapy as demonstrated by the success of the humanized monoclonal antibody Trastuzumab (Herceptin). Resistance to Trastuzumab and eventual failure in most cases, however, necessitate alternate ErbB2-targeted therapies. HSP90 inhibitors such as 17-allylaminodemethoxygeldanamycin (17-AAG), potently downregulate the cell surface ErbB2. While the precise mechanisms of Trastuzumab or 17-AAG action remain unclear, ubiquitinylation-dependent proteasomal or lysosomal degradation of ErbB2 appears to play a substantial role. As Trastuzumab and 17-AAG induce the recruitment of distinct E3 ubiquitin ligases, Cbl and CHIP respectively, to ErbB2, we hypothesized that 17-AAG and Trastuzumab combination could induce a higher level of ubiquitinylation and downregulation of ErbB2 as compared to single drug treatments. We present biochemical and cell biological evidence that combined 17-AAG and Trastuzumab treatment of ErbB2-overexpressing breast cancer cell lines leads to enhanced ubiquitinylation, downregulation from the cell surface and lysosomal degradation of ErbB2. Importantly, combined 17-AAG and Trastuzumab treatment induced synergistic growth arrest and cell death specifically in ErbB2-overexpressing but not in ErbB2-low breast cancer cells. Our results suggest the 17-AAG and Trastuzumab combination as a mechanism-based combinatorial targeted therapy for ErbB2-overexpressing breast cancer patients.

  19. Novel Peptide/Protein Delivery System Targeting erbB2-Overexpressing Breast Cancer Cells

    National Research Council Canada - National Science Library

    Yu, Dihua

    2002-01-01

    .... During this funding year, we focused on the delivery of erbB2 signal-blocking ESP peptides (objective 2) . Because of the complexity of biotin-penetratin-AHNP-ESP, the synthesis was unsuccessful...

  20. Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

    Energy Technology Data Exchange (ETDEWEB)

    Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: federica.cavallo@unito.it [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)

    2011-08-10

    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

  1. ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.

    Science.gov (United States)

    Elizalde, Patricia V; Cordo Russo, Rosalía I; Chervo, Maria F; Schillaci, Roxana

    2016-12-01

    Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies. © 2016 Society for Endocrinology.

  2. Engineering of bispecific affinity proteins with high affinity for ERBB2 and adaptable binding to albumin.

    Directory of Open Access Journals (Sweden)

    Johan Nilvebrant

    Full Text Available The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein.

  3. Breast cancer metastasis driven by ErbB2 and 14-3-3ξ: A division of labor

    OpenAIRE

    Wang, Yingqun

    2010-01-01

    Metastasis remains the leading cause of cancer morbidity and mortality. ErbB2, a metastasis-promoting oncoprotein, is overexpressed in 50–60% of noninvasive ductal carcinoma in situ (DCIS). However, only 25% of invasive breast cancer (IBC) overexpress ErbB2, indicating that ErbB2 alone is not sufficient to drive metastasis and additional risk factors are necessary for the progression of ErbB2-overexpressing DCIS to IBC. A recent study published in Cancer Cell identified 14-3-3ξ as a risk fact...

  4. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

    Directory of Open Access Journals (Sweden)

    Flores Juana M

    2010-07-01

    Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

  5. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

    Science.gov (United States)

    Munisvaradass, Rusheni; Kumar, Suresh; Govindasamy, Chandramohan; Alnumair, Khalid S.; Mok, Pooi Ling

    2017-01-01

    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours. PMID:28885562

  6. Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus

    DEFF Research Database (Denmark)

    Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo

    2007-01-01

    inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent...

  7. ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2015-03-01

    Full Text Available Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

  8. ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.

    Science.gov (United States)

    Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I; Creighton, Chad J; Kheradmand, Farrah; DeMayo, Francesco J

    2015-03-03

    Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Dipankar Ray

    2011-05-01

    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  10. A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Bekaii-Saab, Tanios; Williams, Nita; Plass, Christoph; Calero, Miguel Villalona; Eng, Charis

    2006-01-01

    Several studies showed that gain-of-function somatic mutations affecting the catalytic domain of EGFR in non-small cell lung carcinomas were associated with response to gefitinib and erlotinib, both EGFR-tyrosine kinase inhibitors. In addition, 4% of non-small cell lung carcinomas were shown to have ERBB2 mutations in the kinase domain. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and/or biliary cancers. We extracted genomic DNA from 40 hepatoma (18) and biliary cancers (22) samples, and 44 adenocarcinomas of the lung, this latter as a positive control for mutation detection. We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing targeting exons 18–21 of EGFR and ERBB2. All samples were tested against matched normal DNA. We found 11% of hepatoma, but no biliary cancers, harbored a novel ERBB2 H878Y mutation in the activating domain. These newly described mutations may play a role in predicting response to EGFR-targeted therapy in hepatoma and their role should be explored in prospective studies

  11. OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.

    Directory of Open Access Journals (Sweden)

    Loïc Deleyrolle

    Full Text Available The proliferation and differentiation of neural stem cells are tightly controlled by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly recognized as regulators of these processes. Here we report the expression of the olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM during mouse spinal cord development and in neural stem cells cultured as neurospheres. OCAM is also weakly expressed in the dormant adult stem cell niche around the central canal and is overexpressed after spinal cord injury. Both transmembrane (TM and glycosylphosphatidylinositol (GPI-linked isoforms are present in neurospheres. Electron microscopy and internalisation experiments revealed a dynamic trafficking of OCAM between the membrane and intracellular compartments. After differentiation, OCAM remains in neurons and oligodendrocytes whereas no expression is detected in astrocytes. Using OCAM knockout (KO mice, we found that mutant spinal cord stem cells showed an increased proliferation and self-renewal rates although no effect on differentiation was observed. This effect was reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced proliferation of mutant cells. ErbB2 protein expression and phosphorylation level were significantly increased in KO cells whereas no difference was observed at the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also increased their growth while reintroduction of OCAM in mutant cells reduced the level of phosphorylated ErbB2. These results indicate that OCAM exerts a posttranscriptional control on the ErbB2 signalling in spinal cord stem cells. This study adds further support for considering cell adhesion molecules as regulators of the ErbB signalling.

  12. Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells.

    Science.gov (United States)

    Zhang, Yingqiu; Zhang, Jinrui; Liu, Congcong; Du, Sha; Feng, Lu; Luan, Xuelin; Zhang, Yayun; Shi, Yulin; Wang, Taishu; Wu, Yue; Cheng, Wei; Meng, Songshu; Li, Man; Liu, Han

    2016-11-28

    Receptor tyrosine kinase ErbB2/HER2 is frequently observed to be overexpressed in human cancers, leading to over activation of downstream signaling modules. HER2 positive is a major type of breast cancer for which ErbB2 targeting is already proving to be an effective therapeutic strategy. Apart from antibodies against ErbB2, the small molecule tyrosine kinase inhibitor lapatinib has had successful clinical outcomes, and other inhibitors such as neratinib are currently undergoing clinical investigations. In this study we report the effects of lapatinib and neratinib on the mRNA and protein levels of the ErbB2 receptor. We provide evidence that neratinib-induced down regulation of ErbB2 occurs through ubiquitin-mediated endocytic sorting and lysosomal degradation. At the mechanistic level, neratinib treatment leads to HSP90 release from ErbB2 and its subsequent ubiquitylation and endocytic degradation. Our findings provide novel insights into the mechanism of ErbB2 inhibition by neratinib. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel

    2012-01-01

    Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

  14. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

    Science.gov (United States)

    Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

    2015-06-28

    ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

  15. Poly (A+ transcriptome assessment of ERBB2-induced alterations in breast cell lines.

    Directory of Open Access Journals (Sweden)

    Dirce Maria Carraro

    Full Text Available We report the first quantitative and qualitative analysis of the poly (A⁺ transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples. Moreover, comparative analysis showed enrichment in alternative events, especially in the exon usage category, in ERBB2 over-expressing cells, data indicating regulation of alternative splicing mediated by the oncogene. Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME revealed by large-scale sequencing were confirmed between cell lines as well as in tumor specimens with different ERBB2 backgrounds. This approach was shown to be suitable for structural, quantitative, and qualitative assessment of complex transcriptomes and revealed new events mediated by ERBB2 overexpression, in addition to potential molecular targets for breast cancer that are driven by this oncogene.

  16. Recent advances in long wavelength quantum dot lasers and amplifiers

    NARCIS (Netherlands)

    Nötzel, R.; Bente, E.A.J.M.; Smit, M.K.; Dorren, H.J.S.

    2009-01-01

    We demonstrate 1.55-µm InAs/InGaAsP/InP (100) quantum dot (QD) shallow and deep etched Fabry-Pérot and ring lasers, micro-ring lasers, mode-locked lasers, Butt-joint integrated lasers, polarization control of gain, and wavelength conversion in QD amplifiers.

  17. CRISPR-assisted receptor deletion reveals distinct roles for ERBB2 and ERBB3 in skin keratinocytes.

    Science.gov (United States)

    Dahlhoff, Maik; Gaborit, Nadège; Bultmann, Sebastian; Leonhardt, Heinrich; Yarden, Yosef; Schneider, Marlon R

    2017-10-01

    While the epidermal growth factor receptor (EGFR) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors ERBB2 and ERBB3 in this tissue have only recently been examined. Previously reported, skin-specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both ERBB2 and ERBB3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes. Here, we employed the CRISPR/Cas9 technology to generate HaCaT cells (an established human keratinocyte cell line) lacking ERBB2 or ERBB3. HaCaT clones lacking ERBB2 or ERBB3 showed comparable reductions in cell proliferation as assessed by BrdU staining. Apoptosis, in contrast, was reduced in ERBB3-deficient HaCaT cells only. Assessment of cell migration using a wound healing (scratch) assay showed that the closure of the wound gaps was completed by 48 h in mock and in ERBB3 knockout clones. In contrast, this process was considerably delayed in ERBB2 knockout clones, and a complete closure of the gap in the latter cells did not occur before 72 h. In conclusion, both ERBB2 and ERBB3 are essential for normal proliferation of skin keratinocytes, but in contrast to ERBB3, ERBB2 is essential for migration of human keratinocytes. These observations might bear significance to patient adverse effects of therapeutic agents targeting ERBB2 and ERBB3. © 2017 Federation of European Biochemical Societies.

  18. Microwave dynamic large signal waveform characterization of advanced InGaP HBT for power amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Lixin; Jin Zhi; Liu Xinyu, E-mail: zhaolixin@ime.ac.c [Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029 (China)

    2009-12-15

    In wireless mobile communications and wireless local area networks (WLAN), advanced InGaP HBT with power amplifiers are key components. In this paper, the microwave large signal dynamic waveform characteristics of an advanced InGaP HBT are investigated experimentally for 5.8 GHz power amplifier applications. The microwave large signal waveform distortions at various input power levels, especially at large signal level, are investigated and the reasons are analyzed. The output power saturation is also explained. These analyses will be useful for power amplifier designs. (semiconductor devices)

  19. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    International Nuclear Information System (INIS)

    Schillaci, Roxana; Charreau, Eduardo H; Maronna, Esteban; Roa, Juan C; Elizalde, Patricia V; Guzmán, Pablo; Cayrol, Florencia; Beguelin, Wendy; Díaz Flaqué, María C; Proietti, Cecilia J; Pineda, Viviana; Palazzi, Jorge; Frahm, Isabel

    2012-01-01

    The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration

  20. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana

    2012-02-01

    Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

  1. Activation of EGFR and ERBB2 by Helicobacter pylori Results in Survival of Gastric Epithelial Cells with DNA Damage

    Science.gov (United States)

    Chaturvedi, Rupesh; Asim, Mohammad; Piazuelo, M. Blanca; Yan, Fang; Barry, Daniel P.; Sierra, Johanna Carolina; Delgado, Alberto G.; Hill, Salisha; Casero, Robert A.; Bravo, Luis E.; Dominguez, Ricardo L.; Correa, Pelayo; Polk, D. Brent; Washington, M. Kay; Rose, Kristie L.; Schey, Kevin L.; Morgan, Douglas R.; Peek, Richard M.; Wilson, Keith T.

    2014-01-01

    BACKGROUND & AIMS The gastric cancer-causing pathogen Helicobacter pylori upregulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOXhigh cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. METHODS SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H pylori-infected Egfrwa5 mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. Phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsies from Colombian and Honduran cohorts were analyzed by immunohistochemistry. RESULTS SMOX expression and DNA damage were decreased, and apoptosis increased in H pylori-infected Egfrwa5 mice. H pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damagehigh apoptosislow cells. Phosphoproteomic analysis revealed increased EGFR and ERBB2 signaling. Immunoblot analysis demonstrated the presence of a phosphorylated (p)EGFR–ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damagehigh apoptosislow cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR–ERBB2, and pERBB2 were increased predominantly in tissues demonstrating gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR–ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. CONCLUSIONS In an analysis

  2. Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

    Science.gov (United States)

    Hughes, Juliana Bentes; Rødland, Marianne Skeie; Hasmann, Max; Madshus, Inger Helene; Stang, Espen

    2012-01-01

    ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90) are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only. PMID:24281706

  3. Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

    Directory of Open Access Journals (Sweden)

    Juliana Bentes Hughes

    2012-06-01

    Full Text Available ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90 are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only.

  4. Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

    DEFF Research Database (Denmark)

    Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle

    2015-01-01

    , the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG...... parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left...... ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes...

  5. Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1.

    Science.gov (United States)

    Zsebik, Barbara; Citri, Ami; Isola, Jorma; Yarden, Yosef; Szöllosi, János; Vereb, György

    2006-04-15

    ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in approximately 30-40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5-10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30-40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may indicate that activation of ErbB2 to some extent could counteract the overall cytostatic effect, especially at higher levels of ErbB2 expression. The usual therapeutic dose of trastuzumab did not change the IC50 of 17-AAG on the proliferation of either cell line, but nevertheless decreased overall ErbB2 phosphorylation and at low doses of 17-AAG further decreased cell growth in the sensitive SKBR-3, thus trastuzumab may be a good combination partner to counteract undesired activating effects of 17-AAG.

  6. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  7. Transducer of ERBB2.1 (TOB1) as a Tumor Suppressor: A Mechanistic Perspective.

    Science.gov (United States)

    Lee, Hun Seok; Kundu, Juthika; Kim, Ryong Nam; Shin, Young Kee

    2015-12-15

    Transducer of ERBB2.1 (TOB1) is a tumor-suppressor protein, which functions as a negative regulator of the receptor tyrosine-kinase ERBB2. As most of the other tumor suppressor proteins, TOB1 is inactivated in many human cancers. Homozygous deletion of TOB1 in mice is reported to be responsible for cancer development in the lung, liver, and lymph node, whereas the ectopic overexpression of TOB1 shows anti-proliferation, and a decrease in the migration and invasion abilities on cancer cells. Biochemical studies revealed that the anti-proliferative activity of TOB1 involves mRNA deadenylation and is associated with the reduction of both cyclin D1 and cyclin-dependent kinase (CDK) expressions and the induction of CDK inhibitors. Moreover, TOB1 interacts with an oncogenic signaling mediator, β-catenin, and inhibits β-catenin-regulated gene transcription. TOB1 antagonizes the v-akt murine thymoma viral oncogene (AKT) signaling and induces cancer cell apoptosis by activating BCL2-associated X (BAX) protein and inhibiting the BCL-2 and BCL-XL expressions. The tumor-specific overexpression of TOB1 results in the activation of other tumor suppressor proteins, such as mothers against decapentaplegic homolog 4 (SMAD4) and phosphatase and tensin homolog-10 (PTEN), and blocks tumor progression. TOB1-overexpressing cancer cells have limited potential of growing as xenograft tumors in nude mice upon subcutaneous implantation. This review addresses the molecular basis of TOB1 tumor suppressor function with special emphasis on its regulation of intracellular signaling pathways.

  8. Transducer of ERBB2.1 (TOB1 as a Tumor Suppressor: A Mechanistic Perspective

    Directory of Open Access Journals (Sweden)

    Hun Seok Lee

    2015-12-01

    Full Text Available Transducer of ERBB2.1 (TOB1 is a tumor-suppressor protein, which functions as a negative regulator of the receptor tyrosine-kinase ERBB2. As most of the other tumor suppressor proteins, TOB1 is inactivated in many human cancers. Homozygous deletion of TOB1 in mice is reported to be responsible for cancer development in the lung, liver, and lymph node, whereas the ectopic overexpression of TOB1 shows anti-proliferation, and a decrease in the migration and invasion abilities on cancer cells. Biochemical studies revealed that the anti-proliferative activity of TOB1 involves mRNA deadenylation and is associated with the reduction of both cyclin D1 and cyclin-dependent kinase (CDK expressions and the induction of CDK inhibitors. Moreover, TOB1 interacts with an oncogenic signaling mediator, β-catenin, and inhibits β-catenin-regulated gene transcription. TOB1 antagonizes the v-akt murine thymoma viral oncogene (AKT signaling and induces cancer cell apoptosis by activating BCL2-associated X (BAX protein and inhibiting the BCL-2 and BCL-XL expressions. The tumor-specific overexpression of TOB1 results in the activation of other tumor suppressor proteins, such as mothers against decapentaplegic homolog 4 (SMAD4 and phosphatase and tensin homolog-10 (PTEN, and blocks tumor progression. TOB1-overexpressing cancer cells have limited potential of growing as xenograft tumors in nude mice upon subcutaneous implantation. This review addresses the molecular basis of TOB1 tumor suppressor function with special emphasis on its regulation of intracellular signaling pathways.

  9. A single amino acid substitution is sufficient to modify the mitogenic properties of the epidermal growth factor receptor to resemble that of gp185erbB-2

    DEFF Research Database (Denmark)

    Di Fiore, P P; Helin, K; Kraus, M H

    1992-01-01

    The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxtamembrane regio...

  10. Bloch Surface Waves Biosensors for High Sensitivity Detection of Soluble ERBB2 in a Complex Biological Environment.

    Science.gov (United States)

    Sinibaldi, Alberto; Sampaoli, Camilla; Danz, Norbert; Munzert, Peter; Sonntag, Frank; Centola, Fabio; Occhicone, Agostino; Tremante, Elisa; Giacomini, Patrizio; Michelotti, Francesco

    2017-08-17

    We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of the cancer biomarker ERBB2 in cell lysates. Overexpression of the ERBB2 protein is associated with aggressive breast cancer subtypes. To detect soluble ERBB2, we developed an optical set-up which operates in both label-free and fluorescence modes. The detection approach makes use of a sandwich assay, in which the one-dimensional photonic crystals sustaining Bloch surface waves are modified with monoclonal antibodies, in order to guarantee high specificity during the biological recognition. We present the results of exemplary protein G based label-free assays in complex biological matrices, reaching an estimated limit of detection of 0.5 ng/mL. On-chip and chip-to-chip variability of the results is addressed too, providing repeatability rates. Moreover, results on fluorescence operation demonstrate the capability to perform high sensitive cancer biomarker assays reaching a resolution of 0.6 ng/mL, without protein G assistance. The resolution obtained in both modes meets international guidelines and recommendations (15 ng/mL) for ERBB2 quantification assays, providing an alternative tool to phenotype and diagnose molecular cancer subtypes.

  11. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

    Science.gov (United States)

    Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

    2007-11-01

    Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

  12. A peptide conjugate of vitamin E succinate targets breast cancer cells with high erbB2 expression

    Czech Academy of Sciences Publication Activity Database

    Wang, X. F.; Birringer, M.; Dong, L.F.; Vepřek, Pavel; Low, P.; Swettenham, E.; Stantic, M.; Yuan, L. H.; Zobalová, Renata; Wu, K.; Ledvina, Miroslav; Ralph, S.J.; Neužil, Jiří

    2007-01-01

    Roč. 67, č. 7 (2007), s. 3337-3344 ISSN 0008-5472 R&D Projects: GA MZe QF3115 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : vitamin e E * erbB2 * breast cancer Subject RIV: CC - Organic Chemistry Impact factor: 7.672, year: 2007

  13. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    International Nuclear Information System (INIS)

    Dearth, Robert K; Kuiatse, Isere; Wang, Yu-Fen; Liao, Lan; Hilsenbeck, Susan G; Brown, Powel H; Xu, Jianming; Lee, Adrian V

    2011-01-01

    Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm 3 . For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I

  14. [Recent advances of amplified fragment length polymorphism and its applications in forensic botany].

    Science.gov (United States)

    Li, Cheng-Tao; Li, Li

    2008-10-01

    Amplified fragment length polymorphism (AFLP) is a new molecular marker to detect genomic polymorphism. This new technology has advantages of high resolution, good stability, and reproducibility. Great achievements have been derived in recent years in AFLP related technologies with several AFLP expanded methodologies available. AFLP technology has been widely used in the fields of plant, animal, and microbes. It has become one of the hotspots in Forensic Botany. This review focuses on the recent advances of AFLP and its applications in forensic biology.

  15. Update on HER-2 as a target for cancer therapy: The ERBB2 promoter and its exploitation for cancer treatment

    International Nuclear Information System (INIS)

    Hurst, Helen C

    2001-01-01

    Overexpression of the ERBB2 proto-oncogene is associated with amplification of the gene in breast cancer but increased activity of the promoter also plays a significant role. Members of two transcription factor families (AP-2 and Ets) show increased binding to the promoter in over-expressing cells. Consequently, strategies have been devised to target promoter activity, either through the DNA binding sites for these factors, or through another promoter sequence, a polypurine-polypyrimidine repeat structure. The promoter has also been exploited for its tumour-specific activity to direct the accumulation of cytotoxic compounds selectively within cancer cells. Our current understanding of the ERBB2 promoter is reviewed and the status of these therapeutic avenues is discussed

  16. Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

    Science.gov (United States)

    Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

    2016-01-01

    The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P oral malignant cancer.

  17. [Construction of the lentiviral expression vector for anti-p185(erbB2) mouse/human chimeric antibody].

    Science.gov (United States)

    Liu, Fang; Li, Li; Zhang, Wei; Wang, Qi

    2013-04-01

    This research was to construct the lentiviral expression vector for anti- p185(erbB2) mouse/human chimeric antibody and to determine the expression of the chimeric antibody gene in 293T cells transfected with this vector. The genes (vL and vH) coding light and heavy chain of variable regions of anti-p185(erbB2) mAb and the constant regions of human IgG1 (kappa and gamma1) were cloned with PCR method. The target genes were assembled by three-primers PCR method to obtain the chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was constructed correctly. Then, it was transfected into 293T cells and after 48h, GFP protein expression in 293T cells were detected by fluorescent microscope and the chimeric antibody expression was detected by RT-PCR and direct ELISA. The results showed that after 293T cells were transfected with recombination plasmid, both light and heavy chains of the chimeric antibody genes could express together. The chimeric antibody expressed could bind to p185(erbB2) specifically. This research may lay a sound foundation for further study of anti-p185(erbB2) engineered antibody.

  18. Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

    Science.gov (United States)

    Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

    2010-02-23

    p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

  19. A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

    National Research Council Canada - National Science Library

    Carraway, Kermit

    1998-01-01

    .... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

  20. A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

    National Research Council Canada - National Science Library

    Carraway, Kermit

    1999-01-01

    .... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

  1. Comparative immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary craniopharyngiomas

    International Nuclear Information System (INIS)

    Eshebaa, Gh.E.; Hassan, A.A.

    2015-01-01

    Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the sellar/parasellar region. CPs have been classified into histopathologically, genetically, clinically and prognostically two distinctive subtypes: adamantinomatous and papillary variants. Aim To determine the immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary CPs. Materials and methods β-Catenin, EGFR, ErbB2, and p63 immunostaining was performed on paraffin embedded tissue sections of 25 CPs including 18 adamantinomatous craniopharyngioma (ACP) and 7 cases of papillary craniopharyngiomas (PCPs). Results 17 cases (94%) of ACP exhibited strong nuclear/cytoplasmic expression of β-catenin. On the contrary, all cases of PCP showed exclusively membranous expression (ρ value <0.0001). Regarding EGFR, 15 (83%) and 5 cases (71%) of APC and PCP respectively were positive. On the other hand, only 3 cases (17%) of APC and none of PCP exhibited positivity for ErbB2. p63 over-expression was observed in 16 cases of ACP (89%) and 6 cases of PCP (86%). However, the distribution of p63 staining was diffuse in ACP, while in PCP; the staining was mainly restricted to the basal cell layer. Conclusion Nuclear accumulation of β-catenin is a diagnostic hallmark of the ACP and is very helpful in the differential diagnosis between both ACP and PCP in the setting of small biopsies. Moreover, the restricted nuclear β-catenin accumulation in the cohesive cell clusters within the whorl-like areas supports that aberrant β-catenin expression may play a role in the morphogenesis of ACP.

  2. Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model.

    Science.gov (United States)

    Luo, Li-Ping; Han, Bin; Yu, Xiao-Ping; Chen, Xiang-Yan; Zhou, Jie; Chen, Wei; Zhu, Yan-Feng; Peng, Xiao-Li; Zou, Qiang; Li, Sui-Yan

    2014-01-01

    Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

  3. Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes

    International Nuclear Information System (INIS)

    Pentassuglia, Laura; Graf, Michael; Lane, Heidi; Kuramochi, Yukio; Cote, Gregory; Timolati, Francesco; Sawyer, Douglas B.; Zuppinger, Christian; Suter, Thomas M.

    2009-01-01

    Inhibition of ErbB2 (HER2) with monoclonal antibodies, an effective therapy in some forms of breast cancer, is associated with cardiotoxicity, the pathophysiology of which is poorly understood. Recent data suggest, that dual inhibition of ErbB1 (EGFR) and ErbB2 signaling is more efficient in cancer therapy, however, cardiac safety of this therapeutic approach is unknown. We therefore tested an ErbB1-(CGP059326) and an ErbB1/ErbB2-(PKI166) tyrosine kinase inhibitor in an in-vitro system of adult rat ventricular cardiomyocytes and assessed their effects on 1. cell viability, 2. myofibrillar structure, 3. contractile function, and 4. MAPK- and Akt-signaling alone or in combination with Doxorubicin. Neither CGP nor PKI induced cardiomyocyte necrosis or apoptosis. PKI but not CGP caused myofibrillar structural damage that was additive to that induced by Doxorubicin at clinically relevant doses. These changes were associated with an inhibition of excitation-contraction coupling. PKI but not CGP decreased p-Erk1/2, suggesting a role for this MAP-kinase signaling pathway in the maintenance of myofibrils. These data indicate that the ErbB2 signaling pathway is critical for the maintenance of myofibrillar structure and function. Clinical studies using ErbB2-targeted inhibitors for the treatment of cancer should be designed to include careful monitoring for cardiac dysfunction.

  4. Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation.

    Science.gov (United States)

    Stefanova, Margarita; Zemke, Katrin; Dimitrov, Boyan; Has, Christina; Kern, Johannes S; Bruckner-Tuderman, Leena; Kutsche, Kerstin

    2005-10-01

    Mutations in the type VII collagen gene (COL7A1) cause autosomal recessive and autosomal dominant inherited dystrophic epidermolysis bullosa (DEB). We report a family with three individuals who present blistering, scarring, hypo- and hyperpigmentation, and nail dystrophy suggestive for DEB. Whereas father and son carry a 5;13 translocation, the daughter shows a normal karyotype. Segregation analysis revealed that all affected family members inherited the same COL7A1 allele. Mutation analysis disclosed a heterozygous missense mutation, c.6227G > A (p.G2076D), in COL7A1 in all affected individuals. Delineation of the translocation breakpoints showed that the ERBB2IP (erbb2 interacting protein or Erbin) gene is disrupted in 5q13.1 and GPC6 in 13q32. GPC6 encodes glypican 6 belonging to a family of cell surface heparan sulfate proteoglycans. The binding partners of Erbin, BP230 (BPAG1) and the integrin beta4 subunit, both involved in hemidesmosome (HD) function, and the presence of Erbin in HD suggested that it plays a role in establishment and maintenance of cell-basement membrane adhesions. However, loss of function of one ERBB2IP copy or expression of a putative novel ERBB2IP fusion protein did not apparently modulate the DEB phenotype in both translocation patients. Nonetheless, one cannot yet exclude that ERBB2IP is a candidate for human blistering disorders such as epidermolysis bullosa.

  5. RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

    Science.gov (United States)

    Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

    2018-04-23

    The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

  6. The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

    International Nuclear Information System (INIS)

    Wang Xinming; Gao Xiang; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

    2006-01-01

    Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam

  7. AIDA: A 16-channel amplifier ASIC to read out the advanced implantation detector array for experiments in nuclear decay spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Braga, D. [STFC Rutherford Appleton Laboratory, Didcot, OX11 0QX (United Kingdom); Coleman-Smith, P. J. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Davinson, T. [Dept. of Physics and Astronomy, Univ. of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); Lazarus, I. H. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Page, R. D. [Dept. of Physics, Univ. of Liverpool, Oliver Lodge Laboratory, Liverpool L69 7ZE (United Kingdom); Thomas, S. [STFC Rutherford Appleton Laboratory, Didcot, OX11 0QX (United Kingdom)

    2011-07-01

    We have designed a read-out ASIC for nuclear decay spectroscopy as part of the AIDA project - the Advanced Implantation Detector Array. AIDA will be installed in experiments at the Facility for Antiproton and Ion Research in GSI, Darmstadt. The AIDA ASIC will measure the signals when unstable nuclei are implanted into the detector, followed by the much smaller signals when the nuclei subsequently decay. Implant energies can be as high as 20 GeV; decay products need to be measured down to 25 keV within just a few microseconds of the initial implants. The ASIC uses two amplifiers per detector channel, one covering the 20 GeV dynamic range, the other selectable over a 20 MeV or 1 GeV range. The amplifiers are linked together by bypass transistors which are normally switched off. The arrival of a large signal causes saturation of the low-energy amplifier and a fluctuation of the input voltage, which activates the link to the high-energy amplifier. The bypass transistors switch on and the input charge is integrated by the high-energy amplifier. The signal is shaped and stored by a peak-hold, then read out on a multiplexed output. Control logic resets the amplifiers and bypass circuit, allowing the low-energy amplifier to measure the subsequent decay signal. We present simulations and test results, demonstrating the AIDA ASIC operation over a wide range of input signals. (authors)

  8. Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.

    Science.gov (United States)

    Grabinski, Nicole; Ewald, Florian

    2014-12-01

    Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton's tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer. It is now an FDA-approved drug marketed under the name Imbruvica(TM) (Pharmacyclics, Inc.) and successfully used as an orally administered second-line drug in the treatment of mantle cell lymphoma. Since BTK is predominantly expressed in hematopoietic cells, the sensitivity of solid tumor cells to Ibrutinib has not been analyzed. In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells. Combination indices below 0.25 at 50% inhibition of cell viability were determined by the Chou-Talalay method. Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors. Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.

  9. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Eldridge, Sandy; Guo, Liang; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

    2014-10-01

    Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts.

    Science.gov (United States)

    Mellinghoff, Ingo K; Tran, Chris; Sawyers, Charles L

    2002-09-15

    Experiments with human prostate cancer cell lines have shown that forced overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen-independent growth and increases androgen receptor-transcriptional activity in a ligand-independent fashion. To investigate the relationship between ErbB-RTK signaling and androgen in genetically unmanipulated human prostate cancer, we performed biochemical and biological studies with the dual ErbB1/ErbB2 RTK inhibitor PKI-166 using human prostate cancer xenograft models with isogenic sublines reflecting the transition from androgen-dependent to androgen-independent growth. In the presence of low androgen concentrations, PKI-166 showed profound growth-inhibitory effects on tumor growth, which could be partially reversed by androgen add-back. At physiological androgen concentrations, androgen withdrawal greatly enhanced the ability of PKI-166 to retard tumor growth. The level of extracellular signal-regulated kinase activation correlated with the response to PKI-166 treatment, whereas the expression levels of ErbB1 and ErbB2 did not. These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway.

  11. Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway

    Czech Academy of Sciences Publication Activity Database

    Wang, X.-F.; Witting, P. K.; Salvatore, B.A.; Neužil, Jiří

    2005-01-01

    Roč. 326, č. 4 (2005), s. 282-289 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E analogs * apoptosis * ErbB2 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  12. Screening to Identify Commonly Used Chinese Herbs That Affect ERBB2 and ESR1 Gene Expression Using the Human Breast Cancer MCF-7 Cell Line

    Directory of Open Access Journals (Sweden)

    Jen-Hwey Chiu

    2014-01-01

    Full Text Available Aim. Our aim the was to screen the commonly used Chinese herbs in order to detect changes in ERBB2 and ESR1 gene expression using MCF-7 cells. Methods. Using the MCF-7 human breast cancer cell line, cell cytotoxicity and proliferation were evaluated by MTT and trypan blue exclusion assays, respectively. A luciferase reporter assay was established by transient transfecting MCF-7 cells with plasmids containing either the ERBB2 or the ESR1 promoter region linked to the luciferase gene. Chinese herbal extracts were used to treat the cells at 24 h after transfection, followed by measurement of their luciferase activity. The screening results were verified by Western blotting to measure HER2 and ERα protein expression. Results. At concentrations that induced little cytotoxicity, thirteen single herbal extracts and five compound recipes were found to increase either ERBB2 or ESR1 luciferase activity. By Western blotting, Si-Wu-Tang, Kuan-Shin-Yin, and Suan-Tsao-Ren-Tang were found to increase either HER2 or ERα protein expression. In addition, Ligusticum chuanxiong was shown to have a great effect on ERBB2 gene expression and synergistically with estrogen to stimulate MCF-7 cell growth. Conclusion. Our results provide important information that should affect clinical treatment strategies among breast cancer patients who are receiving hormonal or targeted therapies.

  13. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin mRNA and protein are up-regulated in IH, but not in SH. ●IH-induced erbB2 phosphorylation is attenuated by erbB2 inhibitor. ●EGF family and erbB2 receptor may be involved in IH-induced cell proliferation.

  14. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    International Nuclear Information System (INIS)

    Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

    2013-01-01

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin mRNA and protein are up-regulated in IH, but not in SH. ●IH-induced erbB2 phosphorylation is attenuated by erbB2 inhibitor. ●EGF family and erbB2 receptor may be involved in IH-induced cell proliferation

  15. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

    Directory of Open Access Journals (Sweden)

    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL. Conclusion Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.

  16. The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration.

    Directory of Open Access Journals (Sweden)

    Ketan Mathavan

    Full Text Available During development, a multi-potent group of cells known as the cranial neural crest (CNC migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3 is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors.

  17. Design and Development of Advanced Lock-in Amplifier and its Application

    Directory of Open Access Journals (Sweden)

    Bhagyajyothi

    2013-06-01

    Full Text Available Lock-in amplifiers are used to process the analog signals even in the presence of noise sources of greater amplitude. In the present study, an attempt is made to design a C8051F060 microcontroller based lock-in amplifier. The microcontroller contains all the on-chip features to design a single-chip lock-in amplifier. The reference signal for lock-in amplifier is generated by on-chip digital-to-analog converter (DAC and timer. The signal whose amplitude is to be measured is acquired by on-chip ADC. The ADC values are directly stored on to XRAM through on-chip DMA controller. Later, these stored values are processed by using quadrature sampling method to get amplitude and phase of the 100 waves. The amplitude and phase values of 100 waves are averaged to eliminate the random noise of the signal and are displayed on the LCD module. The amplitude and phase are sent to the PC through on-chip serial port (UART to store/plot the graph. The proposed lock-in amplifier is applied to study the phase transitions of sulfur sample by varying the temperature at slow rate (0.3 °C/min using microcontroller based temperature control system.

  18. Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 ampersand erbB-2 expression

    International Nuclear Information System (INIS)

    Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

    1994-01-01

    One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman's risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185 erbB2 ) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer

  19. ErbB2 regulates NHEJ repair pathway by affecting erbB1-triggered IR-induced Akt activity

    International Nuclear Information System (INIS)

    Toulany, Mahmoud; Peter Rodemann, H.

    2009-01-01

    We have already reported that erbBl-PI3K-AKT signaling is an important pathway in regulating radiation sensitivity and DNA double strand break repair of human tumor cells. In the present study using small interfering RNA and pharmacological inhibitors in non-small cell lung cancer cell lines we investigated the role of Aktl on radiation-induced DNA-PKcs activity and DNA-double strand break (DNA-DSB) repair. Likewise, the function of erbB2 as hetrodimerization partner of erbBl in radiation-induced Akt activity and regulation of DNA-dsb repair through DNA-PKcs was evaluated. In A549 and H460 transfected with AKTl-siRNA radiation-induced phosphorylation of DNA-PKcs the key enzyme regulating NHEJ repair pathway was markedly inhibited. In both cell lines downregulation of Aktl led to a significant enhancement of residual DNA-DSB, i.e. impaired DNA-DSB repair. Interestingly, in cells transfected with DNA-PKcs-siRNA a lack of effect of AKTl-siRNA on enhancement of residual DNA-DSBs was observed. This results indicate that Aktl regulates NHEJ repair in a DNA-PKcs dependent manner

  20. Self-slowdown and -advancement of fs pulses in a quantum-dot semiconductor optical amplifier

    DEFF Research Database (Denmark)

    Poel, Mike van der; Mørk, Jesper; Hvam, Jørn Märcher

    2005-01-01

    We demonstrate changes in the propagation time of 180 femtosecond pulses in a quantum-dot semiconductor optical amplifier as function of pulse input power and bias current. The results interpreted as a result of pulse reshaping by gain saturation but are also analogous to coherent population osci...

  1. ERBB2 mutation is associated with a worse prognosis in patients with CDH1 altered invasive lobular cancer of the breast.

    Science.gov (United States)

    Ping, Zheng; Siegal, Gene P; Harada, Shuko; Eltoum, Isam-Eldin; Youssef, Mariam; Shen, Tiansheng; He, Jianbo; Huang, Yingjie; Chen, Dongquan; Li, Yiping; Bland, Kirby I; Chang, Helena R; Shen, Dejun

    2016-12-06

    E-cadherin (CDH1) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30-60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC. No significant difference was identified between CDH1-altered and -unaltered ILC cases for any of the examined demographic, clinical or pathologic characteristics, including histologic grade, tumor stage, lymph node metastases, or ER/PR/HER2 states. Seven recurrent mutations (PTEN, MUC16, ERBB2, FAT4, PCDHGA2, HERC1 and FLNC) and four chromosomal changes with recurrent copy number variation (CNV) (11q13, 17q12-21, 8p11 and 8q11) were found in ILC, which correlated with a positive or negative CDH1 alteration status, respectively. The prevalence of the most common breast cancer driver abnormalities including TP53 and PIK3CA mutations and MYC and ERBB2 amplifications showed no difference between the two groups. However, CDH1-altered ILC with an ERBB2 mutation shows a significantly worse prognosis compared to its counterparts without such a mutation. Our study suggests that CDH1-altered ILC patients with ERBB2 mutations may represent an actionable group of patients who could benefit from targeted breast cancer therapy.

  2. Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

    International Nuclear Information System (INIS)

    Cicenas, Jonas; Urban, Patrick; Vuaroqueaux, Vincent; Labuhn, Martin; Küng, Willy; Wight, Edward; Mayhew, Mark; Eppenberger, Urs; Eppenberger-Castori, Serenella

    2005-01-01

    Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers. Using a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated (P-S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients. Akt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the significance of this correlation increased (P < 0.001) in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers (e.g. thymidylate synthase), measured using quantitative real-time RT-PCR. Our findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours

  3. Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

    International Nuclear Information System (INIS)

    Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

    2003-01-01

    The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

  4. Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Chimeric Antigen Receptor

    Science.gov (United States)

    Schönfeld, Kurt; Sahm, Christiane; Zhang, Congcong; Naundorf, Sonja; Brendel, Christian; Odendahl, Marcus; Nowakowska, Paulina; Bönig, Halvard; Köhl, Ulrike; Kloess, Stephan; Köhler, Sylvia; Holtgreve-Grez, Heidi; Jauch, Anna; Schmidt, Manfred; Schubert, Ralf; Kühlcke, Klaus; Seifried, Erhard; Klingemann, Hans G; Rieger, Michael A; Tonn, Torsten; Grez, Manuel; Wels, Winfried S

    2015-01-01

    Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant procedures, we generated a stable clonal cell line expressing a humanized CAR based on ErbB2-specific antibody FRP5 harboring CD28 and CD3ζ signaling domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing tumor cells in vitro and exhibited serial target cell killing. Specific recognition of tumor cells and antitumor activity were retained in vivo, resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell carcinoma model, respectively. γ-irradiation as a potential safety measure for clinical application prevented NK cell replication, while antitumor activity was preserved. Our data demonstrate that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as a promising candidate for use in adoptive cancer immunotherapy. PMID:25373520

  5. RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Anxin Gu

    Full Text Available Radiation-induced heart disease (RIHD, which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

  6. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018. Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.

  7. Advanced design and characterization methodologies for memory-aware CMOS power-amplifier implementation

    Directory of Open Access Journals (Sweden)

    M. Schleyer

    2017-09-01

    Full Text Available This paper reports on an effective root-cause analysis method of memory effects in power amplifiers, as well as introduces compensation techniques on a circuit design level. Despite conventional memory-effect approaches, the discussed method uses a two-tone scan over a wide operation and modulation range. This enables an in-depth study of physical causes and helps to implement compensation techniques at design stage. On the one hand, this circuit investigation is optimized using an automated SystemC model parametrized with real device and measurement values. Hence, computation time is widely reduced which shortens design cycles. On the other hand, the implementation of the derived circuit compensation means will reduce the complexity of digital pre-distortion due to a reduced memory-effect induced AM/AM and AM/PM hysteresis. The approach is demonstrated on a 65 nm CMOS power amplifier with an OIP1 of 27 dBm and a PAE of over 30 % using WCDMA and LTE signals. In fact, mismatch could be reduced by more than 8 %.

  8. Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach.

    Science.gov (United States)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-10-01

    To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes

  9. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    International Nuclear Information System (INIS)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-01-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  10. Performance of the advanced photon source (APS) linac beam position monitors (BPMs) with logarithmic amplifier electronics

    International Nuclear Information System (INIS)

    Fuja, R.E.; White, M.

    1995-01-01

    This paper discusses the performance of the logarithmic amplifier electronics system used with stripline BPMs to measure electron and positron beam positions at the APS linac. The 2856-MHz, S-band linac accelerates 30-nsec pulses of 1.7 A of electrons to 200 MeV, and focuses them onto a positron conversion target. The resulting 8 mA of positrons are further accelerated to 450 MeV by the positron linac. Beam position resolutions of 50 μm are easily obtainable in both the electron and positron linacs. The resolution of the 12-bit A/D converters limits the ultimate beam positron resolution to between 20 and 30 μm at this time

  11. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling

    Science.gov (United States)

    Wang, Linlin; Schulz, Thomas C.; Sherrer, Eric S.; Dauphin, Derek S.; Shin, Soojung; Nelson, Angelique M.; Ware, Carol B.; Zhan, Mei; Song, Chao-Zhong; Chen, Xiaoji; Brimble, Sandii N.; McLean, Amanda; Galeano, Maria J.; Uhl, Elizabeth W.; D'Amour, Kevin A.; Chesnut, Jonathan D.; Rao, Mahendra S.

    2007-01-01

    Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs. PMID:17761519

  12. 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

  13. An AC modulated near infrared gain calibration system for a "Violin-Mode" transimpedance amplifier, intended for advanced LIGO suspensions

    Science.gov (United States)

    Lockerbie, N. A.; Tokmakov, K. V.

    2016-07-01

    The background to this work was a prototype shadow sensor, which was designed for retro-fitting to an advanced LIGO (Laser Interferometer Gravitational wave Observatory) test-mass/mirror suspension, in which a 40 kg test-mass/mirror is suspended by four approximately 600 mm long by 0.4 mm diameter fused-silica suspension fibres. The shadow sensor comprised a LED source of Near InfraRed (NIR) radiation, and a "tall-thin" rectangular silicon photodiode detector, which together were to bracket the fibre under test. The photodiode was positioned so as to be sensitive (primarily) to transverse "Violin-Mode" vibrations of such a fibre, via the oscillatory movement of the shadow cast by the fibre, as this moved across the face of the detector. In this prototype shadow sensing system the photodiode was interfaced to a purpose-built transimpedance amplifier, this having both AC and DC outputs. A quasi-static calibration was made of the sensor's DC responsivity, i.e., incremental rate of change of output voltage versus fibre position, by slowly scanning a fused-silica fibre sample transversely through the illuminating beam. The work reported here concerns the determination of the sensor's more important AC (Violin-Mode) responsivity. Recognition of the correspondence between direct AC modulation of the source, and actual Violin-Mode signals, and of the transformative role of the AC/DC gain ratio for the amplifier, at any modulation frequency, f, resulted in the construction of the AC/DC calibration source described here. A method for determining in practice the transimpedance AC/DC gain ratio of the photodiode and amplifier, using this source, is illustrated by a specific numerical example, and the gain ratio for the prototype sensing system is reported over the frequency range 1 Hz-300 kHz. In fact, a maximum DC responsivity of 1.26 kV.m-1 was measured using the prototype photodiode sensor and amplifier discussed here. Therefore, the measured AC/DC transimpedance gain ratio

  14. An AC modulated near infrared gain calibration system for a "Violin-Mode" transimpedance amplifier, intended for advanced LIGO suspensions.

    Science.gov (United States)

    Lockerbie, N A; Tokmakov, K V

    2016-07-01

    The background to this work was a prototype shadow sensor, which was designed for retro-fitting to an advanced LIGO (Laser Interferometer Gravitational wave Observatory) test-mass/mirror suspension, in which a 40 kg test-mass/mirror is suspended by four approximately 600 mm long by 0.4 mm diameter fused-silica suspension fibres. The shadow sensor comprised a LED source of Near InfraRed (NIR) radiation, and a "tall-thin" rectangular silicon photodiode detector, which together were to bracket the fibre under test. The photodiode was positioned so as to be sensitive (primarily) to transverse "Violin-Mode" vibrations of such a fibre, via the oscillatory movement of the shadow cast by the fibre, as this moved across the face of the detector. In this prototype shadow sensing system the photodiode was interfaced to a purpose-built transimpedance amplifier, this having both AC and DC outputs. A quasi-static calibration was made of the sensor's DC responsivity, i.e., incremental rate of change of output voltage versus fibre position, by slowly scanning a fused-silica fibre sample transversely through the illuminating beam. The work reported here concerns the determination of the sensor's more important AC (Violin-Mode) responsivity. Recognition of the correspondence between direct AC modulation of the source, and actual Violin-Mode signals, and of the transformative role of the AC/DC gain ratio for the amplifier, at any modulation frequency, f, resulted in the construction of the AC/DC calibration source described here. A method for determining in practice the transimpedance AC/DC gain ratio of the photodiode and amplifier, using this source, is illustrated by a specific numerical example, and the gain ratio for the prototype sensing system is reported over the frequency range 1 Hz-300 kHz. In fact, a maximum DC responsivity of 1.26 kV.m(-1) was measured using the prototype photodiode sensor and amplifier discussed here. Therefore, the measured AC/DC transimpedance gain

  15. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... between the subgroups are less well characterized. The molecular subtypes are associated with different risk of metastatic recurrence of the disease. Nevertheless, the performance of these overall patterns to predict outcome is far from optimal, suggesting that biological mechanisms that extend beyond...

  16. Fiber Amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten

    2017-01-01

    The chapter provides a discussion of optical fiber amplifiers and through three sections provides a detailed treatment of three types of optical fiber amplifiers, erbium doped fiber amplifiers (EDFA), Raman amplifiers, and parametric amplifiers. Each section comprises the fundamentals including...... the basic physics and relevant in-depth theoretical modeling, amplifiers characteristics and performance data as a function of specific operation parameters. Typical applications in fiber optic communication systems and the improvement achievable through the use of fiber amplifiers are illustrated....

  17. Coamplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy

    Science.gov (United States)

    Floros, Konstantinos V.; Hu, Bin; Monterrubio, Carles; Hughes, Mark T.; Wells, Jason D.; Morales, Cristina Bernadó; Ghotra, Maninderjit S.; Costa, Carlotta; Souers, Andrew J.; Boikos, Sosipatros A.; Leverson, Joel D.; Tan, Ming; Serra, Violeta; Koblinski, Jennifer E.; Arribas, Joaquin; Prat, Aleix; Paré, Laia; Miller, Todd W.; Harada, Hisashi; Windle, Brad E.; Scaltriti, Maurizio; Faber, Anthony C.

    2018-01-01

    HER2 (ERBB2) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR-mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment. Exploring possible intrinsic causes for this lack of response, we uncovered remarkably depressed levels of NOXA, an endogenous inhibitor of the antiapoptotic MCL-1, in HER2-amplified breast cancer. Upon investigation of the mechanism leading to low NOXA, we identified a micro-RNA encoded in an intron of HER2, termed miR-4728, that targets the mRNA of the Estrogen Receptor α (ESR1). Reduced ESR1 expression in turn prevents ERα-mediated transcription of NOXA, mitigating apoptosis following treatment with the HER2i lapatinib. Importantly, resistance can be overcome with pharmacological inhibition of MCL-1. More generally, while many cancers like EGFR-mutant lung cancer are driven by activated kinases that when drugged lead to robust monotherapeutic responses, we demonstrate that the efficacy of targeted therapies directed against oncogenes active through focal amplification may be mitigated by coamplified genes. PMID:29476008

  18. Advancements in Kinetic Inductance Detector, Spectrometer, and Amplifier Technologies for Millimeter-Wave Astronomy

    Science.gov (United States)

    Che, George

    The inductance of a conductor expresses its tendency to oppose a change in current flowing through it. For superconductors, in addition to the familiar magnetic inductance due to energy stored in the magnetic field generated by this current, kinetic inductance due to inertia of charge carriers is a significant and often dominant contribution to total inductance. Devices based on modifying the kinetic inductance of thin film superconductors have widespread application to millimeter-wave astronomy. Lithographically patterning such a film into a high quality factor resonator produces a high sensitivity photodetector known as a kinetic inductance detector (KID), which is sensitive to frequencies above the superconducting energy gap of the chosen material. Inherently multiplexable in the frequency domain and relatively simple to fabricate, KIDs pave the way to the large format focal plane array instruments necessary to conduct the next generation of cosmic microwave background (CMB), star formation, and galaxy evolution studies. In addition, non-linear kinetic inductance can be exploited to develop traveling wave kinetic inductance parametric amplifiers (TKIPs) based on superconducting delay lines to read out these instruments. I present my contributions to both large and small scale collaborative efforts to develop KID arrays, spectrometers integrated with KIDs, and TKIPs. I optimize a dual polarization TiN KID absorber for the next generation Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry, which is designed to investigate the role magnetic fields play in star formation. As part of an effort to demonstrate aluminum KIDs on sky for CMB polarimetry, I fabricate devices for three design variants. SuperSpec and WSpec are respectively the on-chip and waveguide implementations of a filter bank spectrometer concept designed for survey spectroscopy of high redshift galaxies. I provide a robust tool for characterizing the performance of all Super

  19. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial.

    Science.gov (United States)

    Awada, Ahmad; Colomer, Ramon; Inoue, Kenichi; Bondarenko, Igor; Badwe, Rajendra A; Demetriou, Georgia; Lee, Soo-Chin; Mehta, Ajay O; Kim, Sung-Bae; Bachelot, Thomas; Goswami, Chanchal; Deo, Suryanarayan; Bose, Ron; Wong, Alvin; Xu, Feng; Yao, Bin; Bryce, Richard; Carey, Lisa A

    2016-12-01

    Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was

  20. Reliable PCR quantitation of estrogen, progesterone and ERBB2 receptor mRNA from formalin-fixed, paraffin-embedded tissue is independent of prior macro-dissection

    DEFF Research Database (Denmark)

    Tramm, Trine; Hennig, Guido; Kyndi, Marianne

    2013-01-01

    Gene expression analysis on messenger RNA (mRNA) purified from formalin-fixed, paraffin-embedded tissue is increasingly used for research purposes. Tissue heterogeneity may question specificity and interpretation of results from mRNA isolated from a whole slide section, and thresholds for minimal...... tumor content in the paraffin block or macrodissection are used to avoid contamination from non-neoplastic tissue. The aim was to test if mRNA from tissue surrounding breast cancer affected quantification of estrogen receptor α (ESR1), progesterone receptor (PGR) and human epidermal growth factor...... receptor 2 (ERBB2), by comparing gene expression from whole slide and tumor-enriched sections, and correlating gene expression from whole slide sections with corresponding immunohistochemistry. Gene expression, based on mRNA extracted from a training set (36 paraffin blocks) and two validation sets (133...

  1. A low-noise transimpedance amplifier for the detection of "Violin-Mode" resonances in advanced Laser Interferometer Gravitational wave Observatory suspensions

    Science.gov (United States)

    Lockerbie, N. A.; Tokmakov, K. V.

    2014-11-01

    This paper describes the design and performance of an extremely low-noise differential transimpedance amplifier, which takes its two inputs from separate photodiodes. The amplifier was planned to serve as the front-end electronics for a highly sensitive shadow-displacement sensing system, aimed at detecting very low-level "Violin-Mode" (VM) oscillations in 0.4 mm diameter by 600 mm long fused-silica suspension fibres. Four such highly tensioned fibres support the 40 kg test-masses/mirrors of the Advanced Laser Interferometer Gravitational wave Observatory interferometers. This novel design of amplifier incorporates features which prevent "noise-gain peaking" arising from large area photodiode (and cable) capacitances, and which also usefully separate the DC and AC photocurrents coming from the photodiodes. In consequence, the differential amplifier was able to generate straightforwardly two DC outputs, one per photodiode, as well as a single high-gain output for monitoring the VM oscillations—this output being derived from the difference of the photodiodes' two, naturally anti-phase, AC photocurrents. Following a displacement calibration, the amplifier's final VM signal output was found to have an AC displacement responsivity at 500 Hz of (9.43 ± 1.20) MV(rms) m-1(rms), and, therefore, a shot-noise limited sensitivity to such AC shadow- (i.e., fibre-) displacements of (69 ± 13) picometres/√Hz at this frequency, over a measuring span of ±0.1 mm.

  2. A low-noise transimpedance amplifier for the detection of “Violin-Mode” resonances in advanced Laser Interferometer Gravitational wave Observatory suspensions

    International Nuclear Information System (INIS)

    Lockerbie, N. A.; Tokmakov, K. V.

    2014-01-01

    This paper describes the design and performance of an extremely low-noise differential transimpedance amplifier, which takes its two inputs from separate photodiodes. The amplifier was planned to serve as the front-end electronics for a highly sensitive shadow-displacement sensing system, aimed at detecting very low-level “Violin-Mode” (VM) oscillations in 0.4 mm diameter by 600 mm long fused-silica suspension fibres. Four such highly tensioned fibres support the 40 kg test-masses/mirrors of the Advanced Laser Interferometer Gravitational wave Observatory interferometers. This novel design of amplifier incorporates features which prevent “noise-gain peaking” arising from large area photodiode (and cable) capacitances, and which also usefully separate the DC and AC photocurrents coming from the photodiodes. In consequence, the differential amplifier was able to generate straightforwardly two DC outputs, one per photodiode, as well as a single high-gain output for monitoring the VM oscillations—this output being derived from the difference of the photodiodes’ two, naturally anti-phase, AC photocurrents. Following a displacement calibration, the amplifier's final VM signal output was found to have an AC displacement responsivity at 500 Hz of (9.43 ± 1.20) MV(rms) m −1 (rms), and, therefore, a shot-noise limited sensitivity to such AC shadow- (i.e., fibre-) displacements of (69 ± 13) picometres/√Hz at this frequency, over a measuring span of ±0.1 mm

  3. A low-noise transimpedance amplifier for the detection of "Violin-Mode" resonances in Advanced Laser Interferometer Gravitational wave Observatory suspensions.

    Science.gov (United States)

    Lockerbie, N A; Tokmakov, K V

    2014-11-01

    This paper describes the design and performance of an extremely low-noise differential transimpedance amplifier, which takes its two inputs from separate photodiodes. The amplifier was planned to serve as the front-end electronics for a highly sensitive shadow-displacement sensing system, aimed at detecting very low-level "Violin-Mode" (VM) oscillations in 0.4 mm diameter by 600 mm long fused-silica suspension fibres. Four such highly tensioned fibres support the 40 kg test-masses/mirrors of the Advanced Laser Interferometer Gravitational wave Observatory interferometers. This novel design of amplifier incorporates features which prevent "noise-gain peaking" arising from large area photodiode (and cable) capacitances, and which also usefully separate the DC and AC photocurrents coming from the photodiodes. In consequence, the differential amplifier was able to generate straightforwardly two DC outputs, one per photodiode, as well as a single high-gain output for monitoring the VM oscillations-this output being derived from the difference of the photodiodes' two, naturally anti-phase, AC photocurrents. Following a displacement calibration, the amplifier's final VM signal output was found to have an AC displacement responsivity at 500 Hz of (9.43 ± 1.20) MV(rms) m(-1)(rms), and, therefore, a shot-noise limited sensitivity to such AC shadow- (i.e., fibre-) displacements of (69 ± 13) picometres/√Hz at this frequency, over a measuring span of ±0.1 mm.

  4. Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

    International Nuclear Information System (INIS)

    Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

    2009-01-01

    An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

  5. Operation amplifier

    NARCIS (Netherlands)

    Tetsuya, Saito; Nauta, Bram

    2008-01-01

    To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. SOLUTION: The operation amplifier comprises: a differential amplifier circuit 1;

  6. ICC Experiment Performance Improvement through Advanced Feedback Controllers for High-Power Low-Cost Switching Power Amplifiers

    International Nuclear Information System (INIS)

    Nelson, Brian A.

    2006-01-01

    Limited resources force most smaller fusion energy research experiments to have little or no feedback control of their operational parameters, preventing achievement of their full operational potential. Recent breakthroughs in high-power switching technologies have greatly reduced feedback-controlled power supply costs, primarily those classified as switching power amplifiers. However, inexpensive and flexible controllers for these power supplies have not been developed. A uClinux-based micro-controller (Analog Devices Blackfin BF537) was identified as having the capabilities to form the base of a digital control system for switching power amplifiers. A control algorithm was created, and a Linux character device driver was written to realize the algorithm. The software and algorithm were successfully tested on a switching power amplifier and magnetic field coil using University of Washington (subcontractor) resources

  7. Antares laser power amplifier

    International Nuclear Information System (INIS)

    Stine, R.D.; Ross, G.F.; Silvernail, C.

    1979-01-01

    The overall design of the Antares laser power amplifier is discussed. The power amplifier is the last stage of amplification in the 100-kJ Antares laser. In the power amplifier a single, cylindrical, grid-controlle, cold-cathode electron gun is surrounded by 12 large-aperture CO 2 electron-beam sustained laser discharge sectors. Each power amplifier will deliver 18 kJ and the six modules used in Antares will produce the required 100 kJ for delivery to the target. A large-scale interaction between optical, mechanical, and electrical disciplines is required to meet the design objectives. Significant component advances required by the power amplifier design are discussed

  8. A low-noise transimpedance amplifier for the detection of “Violin-Mode” resonances in advanced Laser Interferometer Gravitational wave Observatory suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Lockerbie, N. A.; Tokmakov, K. V. [SUPA (Scottish Universities Physics Alliance) Department of Physics, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG (United Kingdom)

    2014-11-15

    This paper describes the design and performance of an extremely low-noise differential transimpedance amplifier, which takes its two inputs from separate photodiodes. The amplifier was planned to serve as the front-end electronics for a highly sensitive shadow-displacement sensing system, aimed at detecting very low-level “Violin-Mode” (VM) oscillations in 0.4 mm diameter by 600 mm long fused-silica suspension fibres. Four such highly tensioned fibres support the 40 kg test-masses/mirrors of the Advanced Laser Interferometer Gravitational wave Observatory interferometers. This novel design of amplifier incorporates features which prevent “noise-gain peaking” arising from large area photodiode (and cable) capacitances, and which also usefully separate the DC and AC photocurrents coming from the photodiodes. In consequence, the differential amplifier was able to generate straightforwardly two DC outputs, one per photodiode, as well as a single high-gain output for monitoring the VM oscillations—this output being derived from the difference of the photodiodes’ two, naturally anti-phase, AC photocurrents. Following a displacement calibration, the amplifier's final VM signal output was found to have an AC displacement responsivity at 500 Hz of (9.43 ± 1.20) MV(rms) m{sup −1}(rms), and, therefore, a shot-noise limited sensitivity to such AC shadow- (i.e., fibre-) displacements of (69 ± 13) picometres/√Hz at this frequency, over a measuring span of ±0.1 mm.

  9. Multiple facets of sialomucin complex/MUC4, a membrane mucin and erbb2 ligand, in tumors and tissues (Y2K update).

    Science.gov (United States)

    Carraway, K L; Price-Schiavi, S A; Komatsu, M; Idris, N; Perez, A; Li, P; Jepson, S; Zhu, X; Carvajal, M E; Carraway, C A

    2000-01-01

    Sialomucin complex (SMC, MUC4) is a high Mr glycoprotein heterodimer, composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. ASGP-2 contains two EGF-like domains and acts as an intramembrane ligand for the receptor tyrosine kinase ErbB2. Transfection studies with SMC DNAs showed that SMC expression could markedly reduce both cell-cell and cell-matrix interactions in vitro and increase the growth of primary tumors and the formation of metastatic foci of human A375 melanoma cells as xenotransplants in nude mice, possibly through the ability to suppress apoptosis. SMC is expressed in most vulnerable epithelia as a protective agent, which is found in both membrane and soluble forms at luminal surfaces and secreted into fluids such as milk and tears. SMC appears to be constitutively expressed by most accessible epithelia, notable exceptions being the mammary gland and uterine luminal epithelium, in which it is tightly regulated during pregnancy. Down-regulation at the luminal uterine surface appears necessary for blastocyst implantation. TGF-b is a potent repressor of SMC expression in the mammary gland and uterus, though by different mechanisms. These combined results suggest that SMC has multiple functions in epithelia and is tightly regulated in those tissues where its special functions are required.

  10. Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Hu Xiaoqu; Su Fengxi; Qin Li; Jia Weijuan; Gong Chang; Yu Fengyan; Guo Jujiang; Song Erwei

    2006-01-01

    Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy

  11. Operation Amplifier

    NARCIS (Netherlands)

    Tetsuya, Saito; Nauta, Bram

    2011-01-01

    PROBLEM TO BE SOLVED: To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. SOLUTION: The operation amplifier comprises: a

  12. Operation Amplifier

    NARCIS (Netherlands)

    Tetsuya, S.; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. ; SOLUTION: The operation amplifier comprises: a

  13. Operational amplifiers

    CERN Document Server

    Dostal, Jiri

    1993-01-01

    This book provides the reader with the practical knowledge necessary to select and use operational amplifier devices. It presents an extensive treatment of applications and a practically oriented, unified theory of operational circuits.Provides the reader with practical knowledge necessary to select and use operational amplifier devices. Presents an extensive treatment of applications and a practically oriented, unified theory of operational circuits

  14. Amplifier Distortion

    Science.gov (United States)

    Keeports, David

    2006-12-01

    By definition, a high fidelity amplifier's instantaneous output voltage is directly proportional to its instantaneous input voltage. While high fidelity is generally valued in the amplification of recorded music, nonlinearity, also known as distortion, is desirable in the amplification of some musical instruments. In particular, guitar amplifiers exploit nonlinearity to increase both the harmonic content and sustain of a guitar's sound. I will discuss how both modifications in sound result from saturation of triode tubes and transistors. Additionally, I will describe the difference in the symmetry of saturation curves for transistors and tubes and the reason why tube guitar amplifiers are generally considered to be superior to solid-state amplifiers. Finally, I will discuss attempts to use solid-state electronics to replicate the sound of tube amplifiers.

  15. miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.

    Science.gov (United States)

    Tang, Xian-ye; Zheng, Wei; Ding, Min; Guo, Kai-jin; Yuan, Feng; Feng, Hu; Deng, Bin; Sun, Wei; Hou, Yang; Gao, Lu

    2016-01-01

    Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

  16. Change in HER2 (ERBB2) gene status after taxane-based chemotherapy for breast cancer: polyploidization can lead to diagnostic pitfalls with potential impact for clinical management.

    Science.gov (United States)

    Valent, Alexander; Penault-Llorca, Frédérique; Cayre, Anne; Kroemer, Guido

    2013-01-01

    The status of the HER2 (ERBB2) gene in breast cancer is not static and may change among the primary tumor, lymph node metastases, and distant metastases. This status change can be a consequence of the natural evolution of the tumor or can be induced by therapy. The HER2 gene status is, in the majority of cases, established at the moment of diagnosis. After chemotherapy, monitoring HER2 status can be a challenge because of ploidy changes induced by drugs. The cytogeneticist or the pathologist can face real difficulties in distinguishing between a true HER2 amplification and HER2 copy number increase by polyploidization. We performed a HER2 genetic examination by fluorescence in situ hybridization (FISH) of invasive breast cancers before and after taxane treatment. The majority of patients (91%) were HER2-negative both at diagnosis and after treatment. Thirty of 344 patients (9%) whose tumors were initially HER2-negative were found by FISH to have supernumerary HER2 gene copies (up to 15 copies) after neoadjuvant chemotherapy. This HER2 copy increase could not be attributed to true gene amplifications and instead reflected polyploidization events, which presumably affected all chromosomes. Indeed, when we used other FISH probes, we found other gene copy numbers to parallel those of HER2. We recommend careful checking of invasive breast carcinomas by supplementary FISH probes if the copy number of the HER2 gene is >6. This procedure allows the discrimination of specific HER2 gene amplifications and global increases in ploidy. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Analog circuit design designing high performance amplifiers

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    The third volume Designing High Performance Amplifiers applies the concepts from the first two volumes. It is an advanced treatment of amplifier design/analysis emphasizing both wideband and precision amplification.

  18. An AC modulated near infrared gain calibration system for a “Violin-Mode” transimpedance amplifier, intended for advanced LIGO suspensions

    International Nuclear Information System (INIS)

    Lockerbie, N. A.; Tokmakov, K. V.

    2016-01-01

    The background to this work was a prototype shadow sensor, which was designed for retro-fitting to an advanced LIGO (Laser Interferometer Gravitational wave Observatory) test-mass/mirror suspension, in which a 40 kg test-mass/mirror is suspended by four approximately 600 mm long by 0.4 mm diameter fused-silica suspension fibres. The shadow sensor comprised a LED source of Near InfraRed (NIR) radiation, and a “tall-thin” rectangular silicon photodiode detector, which together were to bracket the fibre under test. The photodiode was positioned so as to be sensitive (primarily) to transverse “Violin-Mode” vibrations of such a fibre, via the oscillatory movement of the shadow cast by the fibre, as this moved across the face of the detector. In this prototype shadow sensing system the photodiode was interfaced to a purpose-built transimpedance amplifier, this having both AC and DC outputs. A quasi-static calibration was made of the sensor’s DC responsivity, i.e., incremental rate of change of output voltage versus fibre position, by slowly scanning a fused-silica fibre sample transversely through the illuminating beam. The work reported here concerns the determination of the sensor’s more important AC (Violin-Mode) responsivity. Recognition of the correspondence between direct AC modulation of the source, and actual Violin-Mode signals, and of the transformative role of the AC/DC gain ratio for the amplifier, at any modulation frequency, f, resulted in the construction of the AC/DC calibration source described here. A method for determining in practice the transimpedance AC/DC gain ratio of the photodiode and amplifier, using this source, is illustrated by a specific numerical example, and the gain ratio for the prototype sensing system is reported over the frequency range 1 Hz–300 kHz. In fact, a maximum DC responsivity of 1.26 kV.m"−"1 was measured using the prototype photodiode sensor and amplifier discussed here. Therefore, the measured AC

  19. An AC modulated near infrared gain calibration system for a “Violin-Mode” transimpedance amplifier, intended for advanced LIGO suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Lockerbie, N. A.; Tokmakov, K. V. [SUPA (Scottish Universities Physics Alliance) Department of Physics, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG (United Kingdom)

    2016-07-15

    The background to this work was a prototype shadow sensor, which was designed for retro-fitting to an advanced LIGO (Laser Interferometer Gravitational wave Observatory) test-mass/mirror suspension, in which a 40 kg test-mass/mirror is suspended by four approximately 600 mm long by 0.4 mm diameter fused-silica suspension fibres. The shadow sensor comprised a LED source of Near InfraRed (NIR) radiation, and a “tall-thin” rectangular silicon photodiode detector, which together were to bracket the fibre under test. The photodiode was positioned so as to be sensitive (primarily) to transverse “Violin-Mode” vibrations of such a fibre, via the oscillatory movement of the shadow cast by the fibre, as this moved across the face of the detector. In this prototype shadow sensing system the photodiode was interfaced to a purpose-built transimpedance amplifier, this having both AC and DC outputs. A quasi-static calibration was made of the sensor’s DC responsivity, i.e., incremental rate of change of output voltage versus fibre position, by slowly scanning a fused-silica fibre sample transversely through the illuminating beam. The work reported here concerns the determination of the sensor’s more important AC (Violin-Mode) responsivity. Recognition of the correspondence between direct AC modulation of the source, and actual Violin-Mode signals, and of the transformative role of the AC/DC gain ratio for the amplifier, at any modulation frequency, f, resulted in the construction of the AC/DC calibration source described here. A method for determining in practice the transimpedance AC/DC gain ratio of the photodiode and amplifier, using this source, is illustrated by a specific numerical example, and the gain ratio for the prototype sensing system is reported over the frequency range 1 Hz–300 kHz. In fact, a maximum DC responsivity of 1.26 kV.m{sup −1} was measured using the prototype photodiode sensor and amplifier discussed here. Therefore, the measured AC

  20. tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO)

    International Nuclear Information System (INIS)

    Menendez, Javier A; Vazquez-Martin, Alejandro; Garcia-Villalba, Rocio; Carrasco-Pancorbo, Alegria; Oliveras-Ferraros, Cristina; Fernandez-Gutierrez, Alberto; Segura-Carretero, Antonio

    2008-01-01

    The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2) oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO) in cultured human breast cancer cell lines. Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC) was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively. Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+)-pinoresinol and 1-(+)-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans) were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation occurred regardless the molecular mechanism

  1. tabAnti-HER2 (erbB-2 oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO

    Directory of Open Access Journals (Sweden)

    Carrasco-Pancorbo Alegria

    2008-12-01

    Full Text Available Abstract Background The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2 oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO in cultured human breast cancer cell lines. Methods Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively. Results Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+-pinoresinol and 1-(+-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation

  2. Amplified Policymaking

    Science.gov (United States)

    Prince, Katherine; Woempner, Carolyn

    2010-01-01

    This brief examines the policy implications of two drivers of change presented in the "2020 Forecast: Creating the Future of Learning"-- Pattern Recognition and Amplified Organization. These drivers point toward a series of cultural shifts and illuminate how we are developing new ways of organizing, constructing, and managing knowledge.…

  3. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2016-03-01

    Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

  4. European Research on THz Vacuum Amplifiers

    DEFF Research Database (Denmark)

    Brunetti, F.; Cojocarua, C.-S.; de Rossi, A.

    2010-01-01

    The OPTHER (OPtically Driven TeraHertz AmplifiERs) project represents a considerable advancement in the field of high frequency amplification. The design and realization of a THz amplifier within this project is a consolidation of efforts at the international level from the main players...... of the European research, academy and industry in vacuum electronics. This paper describes the status of the project and progress towards the THz amplifier realization....

  5. Tundra shrubification and tree-line advance amplify arctic climate warming: results from an individual-based dynamic vegetation model

    Science.gov (United States)

    Zhang, Wenxin; Miller, Paul A.; Smith, Benjamin; Wania, Rita; Koenigk, Torben; Döscher, Ralf

    2013-09-01

    One major challenge to the improvement of regional climate scenarios for the northern high latitudes is to understand land surface feedbacks associated with vegetation shifts and ecosystem biogeochemical cycling. We employed a customized, Arctic version of the individual-based dynamic vegetation model LPJ-GUESS to simulate the dynamics of upland and wetland ecosystems under a regional climate model-downscaled future climate projection for the Arctic and Subarctic. The simulated vegetation distribution (1961-1990) agreed well with a composite map of actual arctic vegetation. In the future (2051-2080), a poleward advance of the forest-tundra boundary, an expansion of tall shrub tundra, and a dominance shift from deciduous to evergreen boreal conifer forest over northern Eurasia were simulated. Ecosystems continued to sink carbon for the next few decades, although the size of these sinks diminished by the late 21st century. Hot spots of increased CH4 emission were identified in the peatlands near Hudson Bay and western Siberia. In terms of their net impact on regional climate forcing, positive feedbacks associated with the negative effects of tree-line, shrub cover and forest phenology changes on snow-season albedo, as well as the larger sources of CH4, may potentially dominate over negative feedbacks due to increased carbon sequestration and increased latent heat flux.

  6. Tundra shrubification and tree-line advance amplify arctic climate warming: results from an individual-based dynamic vegetation model

    International Nuclear Information System (INIS)

    Zhang Wenxin; Miller, Paul A; Smith, Benjamin; Wania, Rita; Koenigk, Torben; Döscher, Ralf

    2013-01-01

    One major challenge to the improvement of regional climate scenarios for the northern high latitudes is to understand land surface feedbacks associated with vegetation shifts and ecosystem biogeochemical cycling. We employed a customized, Arctic version of the individual-based dynamic vegetation model LPJ-GUESS to simulate the dynamics of upland and wetland ecosystems under a regional climate model–downscaled future climate projection for the Arctic and Subarctic. The simulated vegetation distribution (1961–1990) agreed well with a composite map of actual arctic vegetation. In the future (2051–2080), a poleward advance of the forest–tundra boundary, an expansion of tall shrub tundra, and a dominance shift from deciduous to evergreen boreal conifer forest over northern Eurasia were simulated. Ecosystems continued to sink carbon for the next few decades, although the size of these sinks diminished by the late 21st century. Hot spots of increased CH 4 emission were identified in the peatlands near Hudson Bay and western Siberia. In terms of their net impact on regional climate forcing, positive feedbacks associated with the negative effects of tree-line, shrub cover and forest phenology changes on snow-season albedo, as well as the larger sources of CH 4 , may potentially dominate over negative feedbacks due to increased carbon sequestration and increased latent heat flux. (letter)

  7. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Science.gov (United States)

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer cell lines. Gefitinib, erlotinib and NVP-AEE788 caused a significant growth inhibition in vitro; however, there was a significant difference in efficacy (NVP-AEE788>erlotinib>gefitinib). After 14 days of in-vivo treatment, using the chimeric mouse model, tumors had a significantly reduced volume and mass after NVP-AEE788, but not after erlotinib treatment, as compared with placebo. Reduction of proliferation (signalling via the mitogen-activated protein kinase pathway), induction of apoptosis and inhibition of angiogenesis were the main mechanisms of drug action. No significant reduction of anti-apoptotic AKT phosphorylation, however, occurred, which may be a possible counter mechanism of the tumor. Epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 expression was detectable in biliary tract cancer, and receptor inhibition exerts marked effects on tumor growth in vitro and in vivo, which was strongest for the dual EGFR/ErbB-2 inhibitor NVP-AEE788. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.

  8. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

    DEFF Research Database (Denmark)

    Regan, M.M.; Lykkesfeldt, A.E.; Dell'Orto, P.

    2008-01-01

    Background The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish...... whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. Methods The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug...... for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range

  9. Model-based global sensitivity analysis as applied to identification of anti-cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network

    Science.gov (United States)

    Lebedeva, Galina; Sorokin, Anatoly; Faratian, Dana; Mullen, Peter; Goltsov, Alexey; Langdon, Simon P.; Harrison, David J.; Goryanin, Igor

    2012-01-01

    High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer-related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a refining tool in combinatorial anti-cancer drug discovery. PMID:22085636

  10. The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

    DEFF Research Database (Denmark)

    Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine

    2012-01-01

    We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2...

  11. NASA developments in solid state power amplifiers

    Science.gov (United States)

    Leonard, Regis F.

    1990-01-01

    Over the last ten years, NASA has undertaken an extensive program aimed at development of solid state power amplifiers for space applications. Historically, the program may be divided into three phases. The first efforts were carried out in support of the advanced communications technology satellite (ACTS) program, which is developing an experimental version of a Ka-band commercial communications system. These first amplifiers attempted to use hybrid technology. The second phase was still targeted at ACTS frequencies, but concentrated on monolithic implementations, while the current, third phase, is a monolithic effort that focusses on frequencies appropriate for other NASA programs and stresses amplifier efficiency. The topics covered include: (1) 20 GHz hybrid amplifiers; (2) 20 GHz monolithic MESFET power amplifiers; (3) Texas Instruments' (TI) 20 GHz variable power amplifier; (4) TI 20 GHz high power amplifier; (5) high efficiency monolithic power amplifiers; (6) GHz high efficiency variable power amplifier; (7) TI 32 GHz monolithic power amplifier performance; (8) design goals for Hughes' 32 GHz variable power amplifier; and (9) performance goals for Hughes' pseudomorphic 60 GHz power amplifier.

  12. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

    Science.gov (United States)

    Awada, A; Dirix, L; Manso Sanchez, L; Xu, B; Luu, T; Diéras, V; Hershman, D L; Agrapart, V; Ananthakrishnan, R; Staroslawska, E

    2013-01-01

    Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

  13. Amplifier for nuclear spectrometry

    International Nuclear Information System (INIS)

    Suarez Canner, E.

    1996-01-01

    The spectroscopy amplifier model AE-020 is designed to adjust suitable the pulses coming from nuclear radiation detectors. Due to is capacity and specifications, the amplifier can be used together with high and medium resolution spectroscopy system

  14. Portable musical instrument amplifier

    Science.gov (United States)

    Christian, David E.

    1990-07-24

    The present invention relates to a musical instrument amplifier which is particularly useful for electric guitars. The amplifier has a rigid body for housing both the electronic system for amplifying and processing signals from the guitar and the system's power supply. An input plug connected to and projecting from the body is electrically coupled to the signal amplifying and processing system. When the plug is inserted into an output jack for an electric guitar, the body is rigidly carried by the guitar, and the guitar is operatively connected to the electrical amplifying and signal processing system without use of a loose interconnection cable. The amplifier is provided with an output jack, into which headphones are plugged to receive amplified signals from the guitar. By eliminating the conventional interconnection cable, the amplifier of the present invention can be used by musicians with increased flexibility and greater freedom of movement.

  15. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  16. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2010-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ;SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and can

  17. The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer

    Directory of Open Access Journals (Sweden)

    Natsume Hiroko

    2012-07-01

    Full Text Available Abstract Background Genomic DNA amplification is a genetic factor involved in cancer, and some oncogenes, such as ERBB2, are highly amplified in gastric cancer. We searched for the possible amplification of other genes in gastric cancer. Methods and Results A genome-wide single nucleotide polymorphism microarray analysis was performed using three cell lines of differentiated gastric cancers, and 22 genes (including ERBB2 in five highly amplified chromosome regions (with a copy number of more than 6 were identified. Particular attention was paid to the CRKL gene, the product of which is an adaptor protein containing Src homology 2 and 3 (SH2/SH3 domains. An extremely high CRKL copy number was confirmed in the MKN74 gastric cancer cell line using fluorescence in situ hybridization (FISH, and a high level of CRKL expression was also observed in the cells. The RNA-interference-mediated knockdown of CRKL in MKN74 disclosed the ability of CRKL to upregulate gastric cell proliferation. An immunohistochemical analysis revealed that CRKL protein was overexpressed in 24.4% (88/360 of the primary gastric cancers that were analyzed. The CRKL copy number was also examined in 360 primary gastric cancers using a FISH analysis, and CRKL amplification was found to be associated with CRKL overexpression. Finally, we showed that MKN74 cells with CRKL amplification were responsive to the dual Src/BCR-ABL kinase inhibitor BMS354825, likely via the inhibition of CRKL phosphorylation, and that the proliferation of MKN74 cells was suppressed by treatment with a CRKL-targeting peptide. Conclusion These results suggested that CRKL protein is overexpressed in a subset of gastric cancers and is associated with CRKL amplification in gastric cancer. Furthermore, our results suggested that CRKL protein has the ability to regulate gastric cell proliferation and has the potential to serve as a molecular therapy target for gastric cancer.

  18. The OPTHER Project: Progress toward the THz Amplifier

    DEFF Research Database (Denmark)

    Paoloni, C; Brunetti, F; Di Carlo, A

    2011-01-01

    This paper describes the status of the OPTHER (OPtically driven TeraHertz AmplifiERs) project and progress toward the THz amplifier realization. This project represents a considerable advancement in the field of high frequency amplification. The design and realization of a THz amplifier within...... this project is a consolidation of efforts at the international level from the leading scientific and industrial European organizations working with vacuum electronics....

  19. Modeling and design techniques for RF power amplifiers

    CERN Document Server

    Raghavan, Arvind; Laskar, Joy

    2008-01-01

    The book covers RF power amplifier design, from device and modeling considerations to advanced circuit design architectures and techniques. It focuses on recent developments and advanced topics in this area, including numerous practical designs to back the theoretical considerations. It presents the challenges in designing power amplifiers in silicon and helps the reader improve the efficiency of linear power amplifiers, and design more accurate compact device models, with faster extraction routines, to create cost effective and reliable circuits.

  20. Oscillators and operational amplifiers

    OpenAIRE

    Lindberg, Erik

    2005-01-01

    A generalized approach to the design of oscillators using operational amplifiers as active elements is presented. A piecewise-linear model of the amplifier is used so that it make sense to investigate the eigenvalues of the Jacobian of the differential equations. The characteristic equation of the general circuit is derived. The dynamic nonlinear transfer characteristic of the amplifier is investigated. Examples of negative resistance oscillators are discussed.

  1. FLUIDIC AC AMPLIFIERS.

    Science.gov (United States)

    Several fluidic tuned AC Amplifiers were designed and tested. Interstage tuning and feedback designs are considered. Good results were obtained...corresponding Q’s as high as 12. Element designs and test results of one, two, and three stage amplifiers are presented. AC Modulated Carrier Systems

  2. Auto-Zero Differential Amplifier

    Science.gov (United States)

    Quilligan, Gerard T. (Inventor); Aslam, Shahid (Inventor)

    2017-01-01

    An autozero amplifier may include a window comparator network to monitor an output offset of a differential amplifier. The autozero amplifier may also include an integrator to receive a signal from a latched window comparator network, and send an adjustment signal back to the differential amplifier to reduce an offset of the differential amplifier.

  3. Noise in Optical Amplifiers

    DEFF Research Database (Denmark)

    Jeppesen, Palle

    1997-01-01

    Noise in optical amplifiers is discussed on the basis of photons and electromagntic fields. Formulas for quantum noise from spontaneous emission, signal-spontaneous beat noise and spontaneous-spontaneous beat noise are derived.......Noise in optical amplifiers is discussed on the basis of photons and electromagntic fields. Formulas for quantum noise from spontaneous emission, signal-spontaneous beat noise and spontaneous-spontaneous beat noise are derived....

  4. Electrospun amplified fiber optics.

    Science.gov (United States)

    Morello, Giovanni; Camposeo, Andrea; Moffa, Maria; Pisignano, Dario

    2015-03-11

    All-optical signal processing is the focus of much research aiming to obtain effective alternatives to existing data transmission platforms. Amplification of light in fiber optics, such as in Erbium-doped fiber amplifiers, is especially important for efficient signal transmission. However, the complex fabrication methods involving high-temperature processes performed in a highly pure environment slow the fabrication process and make amplified components expensive with respect to an ideal, high-throughput, room temperature production. Here, we report on near-infrared polymer fiber amplifiers working over a band of ∼20 nm. The fibers are cheap, spun with a process entirely carried out at room temperature, and shown to have amplified spontaneous emission with good gain coefficients and low levels of optical losses (a few cm(-1)). The amplification process is favored by high fiber quality and low self-absorption. The found performance metrics appear to be suitable for short-distance operations, and the large variety of commercially available doping dyes might allow for effective multiwavelength operations by electrospun amplified fiber optics.

  5. Fast pulse amplifier

    International Nuclear Information System (INIS)

    Lepetit, J.; Poussier, E.

    1984-01-01

    This amplifier comprises an inverter transformer, the primary circuit of which receives a pulse and the secondary circuit of which is connected to several amplifying elements in parallel. The inverter transformer is made of coaxial cable segments winded around a magnetic torus; the cable cores connected in series constitute the primary circuit and the braiding of cables, connected in parallel, are the secondary circuit. The transformer comprises, besides, delay lines in series with each braiding of the secondary circuit, these ones are such that pulses issued from each braiding arrive together to the secondary circuit connectors. This invention applies, noticeably in the case of a high voltage amplifier, to the control of deflection blocks of particles used in medicine or in particle accelerators [fr

  6. Fast logarithmic amplifier

    International Nuclear Information System (INIS)

    Tai, I.; Hasegawa, K.

    1975-01-01

    This paper reports on the improvement of frequency characteristics of a logarithmic amplifier with a Paterson transdiode connection. The improvement of the response speed has been achieved by using a phase compensation technique. Small signal response analyses of the logging circuit revealed the effects of a series resistor Rsub(p) and a parallel capacitance Csub(p) on the response of the circuit. The improvement of the frequency characteristics are remarkable at higher current levels. These facts were proved by the practical logarithmic amplifier. (auth.)

  7. Amplifying genetic logic gates.

    Science.gov (United States)

    Bonnet, Jerome; Yin, Peter; Ortiz, Monica E; Subsoontorn, Pakpoom; Endy, Drew

    2013-05-03

    Organisms must process information encoded via developmental and environmental signals to survive and reproduce. Researchers have also engineered synthetic genetic logic to realize simpler, independent control of biological processes. We developed a three-terminal device architecture, termed the transcriptor, that uses bacteriophage serine integrases to control the flow of RNA polymerase along DNA. Integrase-mediated inversion or deletion of DNA encoding transcription terminators or a promoter modulates transcription rates. We realized permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control signal ranges and sequential logic supporting autonomous cell-cell communication of DNA encoding distinct logic-gate states. The single-layer digital logic architecture developed here enables engineering of amplifying logic gates to control transcription rates within and across diverse organisms.

  8. Flashlamp excited fluid laser amplified

    International Nuclear Information System (INIS)

    1976-01-01

    The patent describes a laser amplifier with chambers for containing and amplifying an intensifier medium. It serves the need for a large impulse repetition rate and high intensities as required e.g. for laser isotope separation

  9. Improved-Bandwidth Transimpedance Amplifier

    Science.gov (United States)

    Chapsky, Jacob

    2009-01-01

    The widest available operational amplifier, with the best voltage and current noise characteristics, is considered for transimpedance amplifier (TIA) applications where wide bandwidth is required to handle fast rising input signals (as for time-of-flight measurement cases). The added amplifier inside the TIA feedback loop can be configured to have slightly lower voltage gain than the bandwidth reduction factor.

  10. Simplified design of IC amplifiers

    CERN Document Server

    Lenk, John

    1996-01-01

    Simplified Design of IC Amplifiers has something for everyone involved in electronics. No matter what skill level, this book shows how to design and experiment with IC amplifiers. For experimenters, students, and serious hobbyists, this book provides sufficient information to design and build IC amplifier circuits from 'scratch'. For working engineers who design amplifier circuits or select IC amplifiers, the book provides a variety of circuit configurations to make designing easier.Provides basics for all phases of practical design.Covers the most popular forms for amplif

  11. Wideband amplifier design

    CERN Document Server

    Hollister, Allen L

    2007-01-01

    In this book, the theory needed to understand wideband amplifier design using the simplest models possible will be developed. This theory will be used to develop algebraic equations that describe particular circuits used in high frequency design so that the reader develops a ""gut level"" understanding of the process and circuit. SPICE and Genesys simulations will be performed to show the accuracy of the algebraic models. By looking at differences between the algebraic equations and the simulations, new algebraic models will be developed that include parameters originally left out of the model

  12. Building valve amplifiers

    CERN Document Server

    Jones, Morgan

    2013-01-01

    Building Valve Amplifiers is a unique hands-on guide for anyone working with tube audio equipment--as an electronics hobbyist, audiophile or audio engineer. This 2nd Edition builds on the success of the first with technology and technique revisions throughout and, significantly, a major new self-build project, worked through step-by-step, which puts into practice the principles and techniques introduced throughout the book. Particular attention has been paid to answering questions commonly asked by newcomers to the world of the valve, whether audio enthusiasts tackling their first build or

  13. Superconducting digital logic amplifier

    International Nuclear Information System (INIS)

    Przybysz, J.X.

    1989-01-01

    This paper describes a superconducting digital logic amplifier for interfacing between a Josephson junction logic circuit having output current and a higher voltage semiconductor circuit input. The amplifier comprising: an input terminal for connection to a; an output terminal for connection to a semiconductor circuit input; an input, lower critical current, Josephson junction having first and second terminals; a first series string of at least three lower critical current Josephson junctions. The first series string being connected to the first terminal of the input Josephson junction such that the first series string is in series with the input Josephson junction to provide a series combination. The input terminal being connected to the first terminal of the input Josephson junction, and with the critical current of the lower critical current Josephson junctions of the input Josephson junction and the first series Josephson junctions being less than the output current of the low voltage Josephson junction circuit; a second series string of at least four higher critical current Josephson junctions. The second string being connected in parallel with the series combination to provide parallel strings having an upper common connection and a lower common connection. The lower common connection being connected to the second terminal of the input Josephson junction and the upper common connection being connected to the output terminal; and a pulsed DC current source connected the parallel strings at the upper common connection. The DC current source having a current at least equal to the critical current of the higher critical current Josephson junctions

  14. Cascade energy amplifier

    International Nuclear Information System (INIS)

    Barzilov, A.P.; Gulevich, A.V.; Kukharchuk, O.F.

    2000-01-01

    The technical problem of long-life fission product and minor actinide incineration and production of plutonium fuel in the prospective nuclear systems will arise at significant scales of nuclear power industry development. Subcritical nuclear reactors driven by extemal neutron sources (energy amplifiers) are considered as incinerators of toxicity of complete nuclear industry. In the frames of this concept, the subcritical reactor part consisting of two coupled blanket regions (inner fast neutron spectrum core and outer thermal core) driven by extemal neutron source is discussed. Two types of source are studied: spallation target and 14-MeV fusion bum of micropellets. Liquid metal Pb-Bi is considered as target material and coolant of inner fast core. Thermal core is a heavy-water subcritical reactor of the Candu-type. The fast core is protected from thermal neutrons influence with the boron shield. All reactor technologies used in this concept are tested during years of operation and commercially available. Thus, the cascade energy amplifiers have a set of advantages in comparison with traditional concepts: in energy production, in transmutation efficiency, and in economics. (authors)

  15. Nanoscale electromechanical parametric amplifier

    Science.gov (United States)

    Aleman, Benjamin Jose; Zettl, Alexander

    2016-09-20

    This disclosure provides systems, methods, and apparatus related to a parametric amplifier. In one aspect, a device includes an electron source electrode, a counter electrode, and a pumping electrode. The electron source electrode may include a conductive base and a flexible conductor. The flexible conductor may have a first end and a second end, with the second end of the flexible conductor being coupled to the conductive base. A cross-sectional dimension of the flexible conductor may be less than about 100 nanometers. The counter electrode may be disposed proximate the first end of the flexible conductor and spaced a first distance from the first end of the flexible conductor. The pumping electrode may be disposed proximate a length of the flexible conductor and spaced a second distance from the flexible conductor.

  16. Linear pulse amplifier

    International Nuclear Information System (INIS)

    Tjutju, R.L.

    1977-01-01

    Pulse amplifier is standard significant part of spectrometer. Apart from other type of amplification, it's a combination of amplification and pulse shaping. Because of its special purpose the device should fulfill the following : High resolution is desired to gain a high yield comparable to its actual state of condition. High signal to noise is desired to nhν resolution. High linearity to facilitate calibration. A good overload recovery, in order to the device will capable of analizing a low energy radiation which appear joinly on the high energy fields. Other expections of the device are its economical and practical use its extentive application. For that reason it's built on a standard NIM principle. Taking also into account the above mentioned considerations. High quality component parts are used throughout, while its availability in the domestic market is secured. (author)

  17. Modeling of semiconductor optical amplifiers

    DEFF Research Database (Denmark)

    Mørk, Jesper; Bischoff, Svend; Berg, Tommy Winther

    We discuss the modelling of semiconductor optical amplifiers with emphasis on their high-speed properties. Applications in linear amplification as well as ultrafast optical signal processing are reviewed. Finally, the possible role of quantum-dot based optical amplifiers is discussed.......We discuss the modelling of semiconductor optical amplifiers with emphasis on their high-speed properties. Applications in linear amplification as well as ultrafast optical signal processing are reviewed. Finally, the possible role of quantum-dot based optical amplifiers is discussed....

  18. CERN: Energy amplifier

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Even under the heavy burden of responsibility as CERN's Director General from 1989-3 the fertile mind of Carlo Rubbia the scientist was never still. A long-time Rubbia 'hobby' has been the search for new sources of nuclear energy, exploiting knowledge and skills from high energy physics. An initial objective was to adopt heavy ion techniques to induce controlled thermonuclear fusion, but in 1994 this quest changed direction. Putting the problems of thermonuclear fusion aside, Rubbia began to explore an alternative route to energy production through controlled nuclear fission. The idea is to use a particle accelerator producing neutrons by spallation (interaction of particles with a target) to feed a fuel/moderator assembly where the neutrons multiply by fission chain reactions. If the energy liberated becomes substantially greater than that needed to drive the accelerator, the process has a net gain and becomes selfsupporting. Hence the name ''Energy Amplifier'' (EA). Similar systems for energy production or for nuclear waste incineration have been proposed at Los Alamos and in Japan and Russia, but appear to require the prior development of innovative linear accelerators. For Rubbia's Amplifier, the requisite accelerator is a reasonable extrapolation of an existing cyclotron such that at the Swiss Paul Scherrer Institute. Moreover, the EA would require fuel rods very similar to those of conventional reactors, rather than demand-ing new technology using liquid fuel loops (molten salts) with on-line separation of radioactive products. Unlike a reactor, the EA's fission reaction is not self-sustaining: it is sub-critical and needs a continuous supply of neutrons from the accelerator. This makes Chernobyl-type meltdowns unlikely: if the accelerator stops, the reaction stops too. Another major advantage is that the old dream of using thorium as a fuel is now made possible. Thorium is not itself fissile, but under neutron

  19. Millimeter-wave power amplifiers

    CERN Document Server

    du Preez, Jaco

    2017-01-01

    This book provides a detailed review of millimeter-wave power amplifiers, discussing design issues and performance limitations commonly encountered in light of the latest research. Power amplifiers, which are able to provide high levels of output power and linearity while being easily integrated with surrounding circuitry, are a crucial component in wireless microwave systems. The book is divided into three parts, the first of which introduces readers to mm-wave wireless systems and power amplifiers. In turn, the second focuses on design principles and EDA concepts, while the third discusses future trends in power amplifier research. The book provides essential information on mm-wave power amplifier theory, as well as the implementation options and technologies involved in their effective design, equipping researchers, circuit designers and practicing engineers to design, model, analyze, test and implement high-performance, spectrally clean and energy-efficient mm-wave systems.

  20. Class-E Amplifier Design Improvements for GSM Frequencies

    Directory of Open Access Journals (Sweden)

    Z. Nadir

    2011-06-01

    Full Text Available Efficient power amplifiers are essential in portable battery-operated systems such as mobile phones. Also, the power amplifier (PA is the most power-consuming building block in the transmitter of a portable system. This paper investigates how the efficiency of the power amplifier (which is beneficial for multiple applications in communcation sector can be improved by increasing the efficiency of switching mode class E power amplifiers for frequencies of 900 MHz and 1800 MHz. The paper tackles modeling, design improvements and verification through simulation for higher efficiencies. This is the continuation of previous work by the authors. These nonlinear power amplifiers can only amplify constant-envelope RF signals without introducing significant distortion. Mobile systems such as Advanced Mobile Phone System (AMPS and Global System for Mobile communications (GSM use modulation schemes which generate constant amplitude RF outputs in order to use efficient but nonlinear power amplifiers. Improvements in designs are suggested and higher efficiencies are achieved, to the tune of 67.1% (for 900 MHz and 67.0% (1800 MHz.

  1. Small signal microwave amplifier design

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  2. Final amplifier design and mercury

    International Nuclear Information System (INIS)

    Rose, E.A.; Hanson, D.E.

    1991-01-01

    The final amplifier for the Mercury KrF excimer facility is being designed. The design exercise involves extensive modeling to predict amplifier performance. Models of the pulsed-power system, including a Child-Langmuir diode with closure, electron-beam energy deposition, KrF laser kinetics, amplified spontaneous emission (ASE), a time-dependent laser extraction in the presence of ASE are presented as a design package. The design exercise indicates that the energy objective of Phase I -- 100 joules -- will be met

  3. New Packaging for Amplifier Slabs

    Energy Technology Data Exchange (ETDEWEB)

    Riley, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Thorsness, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Suratwala, T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Steele, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rogowski, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-03-18

    The following memo provides a discussion and detailed procedure for a new finished amplifier slab shipping and storage container. The new package is designed to maintain an environment of <5% RH to minimize weathering.

  4. Operational amplifiers theory and design

    CERN Document Server

    Huijsing, Johan

    2017-01-01

    This proven textbook guides readers to a thorough understanding of the theory and design of operational amplifiers (OpAmps). The core of the book presents systematically the design of operational amplifiers, classifying them into a periodic system of nine main overall configurations, ranging from one gain stage up to four or more stages. This division enables circuit designers to recognize quickly, understand, and choose optimal configurations. Characterization of operational amplifiers is given by macro models and error matrices, together with measurement techniques for their parameters. Definitions are given for four types of operational amplifiers depending on the grounding of their input and output ports. Many famous designs are evaluated in depth, using a carefully structured approach enhanced by numerous figures. In order to reinforce the concepts introduced and facilitate self-evaluation of design skills, the author includes problems with detailed solutions, as well as simulation exercises. Provides te...

  5. TARC: Carlo Rubbia's Energy Amplifier

    CERN Multimedia

    Laurent Guiraud

    1997-01-01

    Transmutation by Adiabatic Resonance Crossing (TARC) is Carlo Rubbia's energy amplifier. This CERN experiment demonstrated that long-lived fission fragments, such as 99-TC, can be efficiently destroyed.

  6. Enhanced performance CCD output amplifier

    Science.gov (United States)

    Dunham, Mark E.; Morley, David W.

    1996-01-01

    A low-noise FET amplifier is connected to amplify output charge from a che coupled device (CCD). The FET has its gate connected to the CCD in common source configuration for receiving the output charge signal from the CCD and output an intermediate signal at a drain of the FET. An intermediate amplifier is connected to the drain of the FET for receiving the intermediate signal and outputting a low-noise signal functionally related to the output charge signal from the CCD. The amplifier is preferably connected as a virtual ground to the FET drain. The inherent shunt capacitance of the FET is selected to be at least equal to the sum of the remaining capacitances.

  7. Advances in Opto Electronics

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Advances in Opto Electronics. Optoelectronics is where electronics was 15 years back. All Optical Amplifiers and Semiconductor Amplifiers. Fastest Semiconductor (InP) switch is at 170GHz- where is terrabit ? MEMS based switches that route traffic at wavelength level ...

  8. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

    Science.gov (United States)

    Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

    2016-03-01

    In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; PCancer 2016;122:702-711. © 2015 American Cancer Society. © 2015 American Cancer Society.

  9. K-Band Traveling-Wave Tube Amplifier

    Science.gov (United States)

    Force, Dale A.; Simons, Rainee N.; Peterson, Todd T.; Spitsen, Paul C.

    2010-01-01

    A new space-qualified, high-power, high-efficiency, K-band traveling-wave tube amplifier (TWTA) will provide high-rate, high-capacity, direct-to-Earth communications for science data and video gathered by the Lunar Reconnaissance Orbiter (LRO) during its mission. Several technological advances were responsible for the successful demonstration of the K-band TWTA.

  10. Spectroscopic amplifier for pin diode

    International Nuclear Information System (INIS)

    Alonso M, M. S.; Hernandez D, V. M.; Vega C, H. R.

    2014-10-01

    The photodiode remains the basic choice for the photo-detection and is widely used in optical communications, medical diagnostics and field of corpuscular radiation. In detecting radiation it has been used for monitoring radon and its progeny and inexpensive spectrometric systems. The development of a spectroscopic amplifier for Pin diode is presented which has the following characteristics: canceler Pole-Zero (P/Z) with a time constant of 8 μs; constant gain of 57, suitable for the acquisition system; 4th integrator Gaussian order to waveform change of exponential input to semi-Gaussian output and finally a stage of baseline restorer which prevents Dc signal contribution to the next stage. The operational amplifier used is the TLE2074 of BiFET technology of Texas Instruments with 10 MHz bandwidth, 25 V/μs of slew rate and a noise floor of 17 nv/(Hz)1/2. The integrated circuit has 4 operational amplifiers and in is contained the total of spectroscopic amplifier that is the goal of electronic design. The results show like the exponential input signal is converted to semi-Gaussian, modifying only the amplitude according to the specifications in the design. The total system is formed by the detector, which is the Pin diode, a sensitive preamplifier to the load, the spectroscopic amplifier that is what is presented and finally a pulse height analyzer (Mca) which is where the spectrum is shown. (Author)

  11. Low-power, enhanced-gain adaptive-biasing-based Operational Transconductance Amplifiers

    DEFF Research Database (Denmark)

    Moradi, Farshad

    A symmetrical PMOS OTA (Operational Transconductance Amplifier) is used to build an advanced rail-to-rail amplifier with improved DC-gain and reduced power consumption. By using the adaptive biasing circuit for two differential inputs, a low stand-by current can be achieved, reducing power...

  12. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens.

    Science.gov (United States)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M; Sahin, Ugur

    2016-07-07

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and

  13. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M.; Sahin, Ugur

    2016-01-01

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and 0

  14. Numerical simulation of cross field amplifiers

    International Nuclear Information System (INIS)

    Eppley, K.

    1990-01-01

    Cross field amplifiers (CFA) have been used in many applications where high power, high frequency microwaves are needed. Although these tubes have been manufactured for decades, theoretical analysis of their properties is not as highly developed as for other microwave devices such as klystrons. One feature distinguishing cross field amplifiers is that the operating current is produced by secondary emission from a cold cathode. This removes the need for a heater and enables the device to act as a switch tube, drawing no power until the rf drive is applied. However, this method of generating the current does complicate the simulation. We are developing a simulation model of cross field amplifiers using the PIC code CONDOR. We simulate an interaction region, one traveling wavelength long, with periodic boundary conditions. An electric field with the appropriate phase velocity is imposed on the upper boundary of the problem. Evaluation of the integral of E·J gives the power interchanged between the wave and the beam. Given the impedance of the structure, we then calculate the change in the traveling wave field. Thus we simulate the growth of the wave through the device. The main advance of our model over previous CFA simulations is the realistic tracking of absorption and secondary emission. The code uses experimental curves to calculate secondary production as a function of absorbed energy, with a theoretical expression for the angular dependence. We have used this code to model the 100 MW X-band CFA under construction at SLAC, as designed by Joseph Feinstein and Terry Lee. We are examining several questions of practical interest, such as the power and spectrum of absorbed electrons, the minimum traveling wave field needed to initiate spoke formation, and the variation of output power with dc voltage, anode-cathode gap, and magnetic field. 5 refs., 8 figs

  15. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

    Science.gov (United States)

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-10-03

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest

  16. Dielectric waveguide amplifiers and lasers

    NARCIS (Netherlands)

    Pollnau, Markus

    The performance of semiconductor amplifiers and lasers has made them the preferred choice for optical gain on a micro-chip. In the past few years, we have demonstrated that also rare-earth-ion-doped dielectric waveguides show remarkable performance, ranging from a small-signal gain per unit length

  17. CMOS Current-mode Operational Amplifier

    DEFF Research Database (Denmark)

    Kaulberg, Thomas

    1992-01-01

    current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain bandwidth product of 8 MHz, an offset current of 0.8 ¿A (signal-range ±700¿A) and a (theoretically) unlimited slew-rate. The amplifier is realized in a standard CMOS 2......A fully differential-input differential-output current-mode operational amplifier (COA) is described. The amplifier utilizes three second generation current-conveyors (CCII) as the basic building blocks. It can be configured to provide either a constant gain-bandwidth product in a fully balanced...

  18. A CMOS current-mode operational amplifier

    DEFF Research Database (Denmark)

    Kaulberg, Thomas

    1993-01-01

    current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain-bandwidth product of 3 MHz, an offset current of 0.8 μA (signal range ±700 μA), and a (theoretically) unlimited slew rate. The amplifier is realized in a standard CMOS 2......A fully differential-input, differential-output, current-mode operational amplifier (COA) is described. The amplifier utilizes three second-generation current conveyors (CCIIs) as the basic building blocks. It can be configured to provide either a constant gain-bandwidth product in a fully balanced...

  19. Current feedback operational amplifiers and their applications

    CERN Document Server

    Senani, Raj; Singh, A K; Singh, V K

    2013-01-01

    This book describes a variety of current feedback operational amplifier (CFOA) architectures and their applications in analog signal processing/generation. Coverage includes a comprehensive survey of commercially available, off-the-shelf integrated circuit CFOAs, as well as recent advances made on the design of CFOAs, including design innovations for bipolar and CMOS CFOAs.  This book serves as a single-source reference to the topic, as well as a catalog of over 200 application circuits which would be useful not only for students, educators and researchers in apprising them about the recent developments in the area but would also serve as a comprehensive repertoire of useful circuits for practicing engineers who might be interested in choosing an appropriate CFOA-based topology for use in a given application.

  20. New developments in relativistic klystron amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, M; Colombant, D; Fernsler, R; Hubbard, R; Lampe, M; Serlin, V; Slinker, S [Naval Research Lab., Washington, DC (United States). Plasma Physics Div.

    1997-12-31

    A relativistic klystron amplifier that employed cavities with inductively loaded wide gaps and a novel converter has achieved 50% energy efficiency, a significant advance over the previous state of the art of 20%. The new device was immersed in a 3 kG magnetic field and contained two innovations: (1) Wide gaps which include an inductively loaded return current structure that was opaque to the unmodulated beam space charge but transparent to the RF field. (2) A novel converter that was made of a `leaky` cavity with a radially-converging inductively-loaded structure that was inserted in the output wide-gap. This structure reduced the potential energy residing in the electron beam and maximized RF output energy. (author). 4 figs., 13 refs.

  1. Amplified spontaneous emissions in a high-gain laser amplifier

    International Nuclear Information System (INIS)

    Osada, Hidenori; Gamo, Hideya.

    1978-01-01

    The gain and line-narrowing of the amplified spontaneous emissions(ASE) in a partially homogeneous high-gain Xe 3.51 μm laser amplifier were studied theoretically and experimentally with emphasis of saturation effect. The unidirectionally travelling ASE was generated by conveniently using optical isolators and used as a broadband radiation source. It has properties of 10 μW/mm 2 in intensity with fluctuation of less than 1% in 5 hours, 43.5 MHz of the linewidth and 1.0 x 10 -3 radians of beam divergence. The measured saturation intensity was 4.85 μW/mm 2 and a small signal gain was 0.1 cm -1 . The theoretical prediction of the line-narrowing shows reasonablly good agreement with the measured one. (author)

  2. Novel Drugs that Target ErbB2

    Science.gov (United States)

    2012-05-01

    of pharmacological properties including antiviral, antibacterial, anti-inflammatory, antimalarial and anticancer activities (1, 2). BA also inhibits...expression and the overall mechanisms associated with the anticancer activity of BA. We also investigated the role of BA in triple-negative MDA-MB-231...expression and the overall mechanisms associated with the anticancer activity of BA. In addition, we also investigated the role of BA in triple-negative

  3. ErbB2-associated changes in the lysosomal proteome

    DEFF Research Database (Denmark)

    Nylandsted, Jesper; Becker, Andrea C; Bunkenborg, Jakob

    2011-01-01

    Late endosomes and lysosomes (hereafter referred to as lysosomes) play an essential role in the turnover of cellular macromolecules and organelles. Their biochemical characterization has so far depended on purification methods based on either density gradient centrifugations or magnetic...... purification of iron-loaded organelles. Owing to dramatic changes in lysosomal density and stability associated with lysosomal diseases and cancer, these methods are not optimal for the comparison of normal and pathological lysosomes. Here, we introduce an efficient method for the purification of intact...... lysosomes by magnetic immunoprecipitation with antibodies against the vacuolar-type H(+) -ATPase. Quantitative MS-based proteomics analysis of the obtained lysosomal membranes identified 60 proteins, most of which have previously been associated with the lysosomal compartment. Interestingly, the lysosomal...

  4. Single conversion stage amplifier - SICAM

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.

    2005-12-15

    This Ph.D. thesis presents a thorough analysis of the so called SICAM - SIngle Converter stage AMplifier approach to building direct energy conversion audio power amplifiers. The mainstream approach for building isolated audio power amplifiers today consists of isolated DC power supply and Class D amplifier, which essentially represents a two stage solution, where each of the components can be viewed as separate and independent part. The proposed SICAM solution strives for direct energy conversion from the mains to the audio output, by dedicating the operation of the components one to another and integrating their functions, so that the final audio power amplifier represents a single-stage topology with higher efficiency, lower volume, less board space, lower component count and subsequently lower cost. The SICAM approach is both applicable to non-isolated and isolated audio power amplifiers, but the problems encountered in these two cases are different. Non-isolated SICAM solutions are intended for both AC mains-connected and battery-powered devices. In non-isolated mains-connected SICAMs the main idea is to simplify the power supply or even provide integrated power factor correction (PFC) functions, while still maintaining low component stress and good audio performance by generally decreasing the input voltage level to the Class D audio power amplifier. On the other hand, non-isolated battery-powered SICAMs have to cope with the ever changing battery voltage and provide output voltage levels which are both lower and higher than the battery voltage, while still being simple and single-stage energy conversion solutions. In isolated SICAMs the isolation transformer adjusts the voltage level on the secondary side to the desired level, so the main challenges here are decreasing the size of the magnetic core and reducing the number and size of bulky reactive components as much as possible. The main focus of this thesis is directed towards the isolated SICAMs and

  5. Higher order mode optical fiber Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Friis, Søren Michael Mørk; Usuga Castaneda, Mario A.

    2016-01-01

    We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations.......We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations....

  6. SPS RF System Amplifier plant

    CERN Multimedia

    1977-01-01

    The picture shows a 2 MW, 200 MHz amplifier plant with feeder lines. The main RF-system of the SPS comprises four cavities: two of 20 m length and two of 16.5 m length. They are all installed in one long straight section (LSS 3). These cavities are of the travelling-wave type operating at a centre frequency of 200.2 MHz. They are wideband, filling time about 700 ns and untuned. The power amplifiers, using tetrodes are installed in a surface building 200 m from the cavities. Initially only two cavities were installed, a third cavity was installed in 1978 and a forth one in 1979. The number of power amplifiers was also increased: to the first 2 MW plant a second 2 MW plant was added and by end 1979 there were 8 500 kW units combined in pairs to feed each of the 4 cavities with up to about 1 MW RF power, resulting in a total accelerating voltage of about 8 MV. See also 7412016X, 7412017X, 7411048X.

  7. Challenges in higher order mode Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Nielsen, Kristian; Friis, Søren Michael Mørk

    2015-01-01

    A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed......A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed...

  8. Integrated amplifying circuit with MOS transistors

    Energy Technology Data Exchange (ETDEWEB)

    Baylac, B; Merckel, G; Meunier, P

    1974-01-25

    The invention relates to a feedback-pass-band amplifier with MOS-transistors. The differential stage of conventional amplifiers is changed into an adding state, whereas the differential amplification stages are changed into amplifier inverter stages. All MOS transistors used in that amplifier are of similar configuration and are interdigitized, whereby the operating speed dispersion is reduced. This can be applied to obtaining a measurement channel for proportional chambers.

  9. A pulse amplifier for nuclear instrumentation

    International Nuclear Information System (INIS)

    Martin, D.; Cliff, P.

    1987-01-01

    A Class-A 1 Watt amplifier has been designed and optimized for nanosecond pulses. Spanning .01MHz to 1300Mhz, signal gain is 26dB with gain flatness of 1dB. The amplifier drive +- 10 volts across 500 with 350ps risetime. Each amplifier is housed in a 2-wide NIM

  10. Remote Acquisition Amplifier For 50-Ohm Cable

    Science.gov (United States)

    Amador, Jose J.

    1995-01-01

    Buffer-amplifier unit designed to drive 50-Ohm cables up to 100 ft. (30 m) long, compensating for attenuation in cables and enabling remote operation of oscilloscopes. Variable resistor provides for adjustment of gain of amplifier, such that overall gain from input terminals of amplifier to output end of cable set to unity.

  11. An Implantable CMOS Amplifier for Nerve Signals

    DEFF Research Database (Denmark)

    Nielsen, Jannik Hammel; Lehmann, Torsten

    2003-01-01

    In this paper, a low noise high gain CMOS amplifier for minute nerve signals is presented. The amplifier is constructed in a fully differential topology to maximize noise rejection. By using a mixture of weak- and strong inversion transistors, optimal noise suppression in the amplifier is achieved....... A continuous-time current-steering offset-compensation technique is utilized in order to minimize the noise contribution and to minimize dynamic impact on the amplifier input nodes. The method for signal recovery from noisy nerve signals is presented. A prototype amplifier is realized in a standard digital 0...

  12. Semiconductor quantum-dot lasers and amplifiers

    DEFF Research Database (Denmark)

    Hvam, Jørn Märcher; Borri, Paola; Ledentsov, N. N.

    2002-01-01

    -power surface emitting VCSELs. We investigated the ultrafast dynamics of quantum-dot semiconductor optical amplifiers. The dephasing time at room temperature of the ground-state transition in semiconductor quantum dots is around 250 fs in an unbiased amplifier, decreasing to below 50 fs when the amplifier...... is biased to positive net gain. We have further measured gain recovery times in quantum dot amplifiers that are significantly lower than in bulk and quantum-well semiconductor optical amplifiers. This is promising for future demonstration of quantum dot devices with high modulation bandwidth...

  13. CMOS Current-mode Operational Amplifier

    OpenAIRE

    Kaulberg, Thomas

    1992-01-01

    A fully differential-input differential-output current-mode operational amplifier (COA) is described. The amplifier utilizes three second generation current-conveyors (CCII) as the basic building blocks. It can be configured to provide either a constant gain-bandwidth product in a fully balanced current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain bandwidth product of 8 MHz, an offset current of 0.8 ¿A (signal-r...

  14. NIF/LMJ prototype amplifier mechanical design

    International Nuclear Information System (INIS)

    Horvath, J.

    1996-10-01

    Amplifier prototypes for the National Ignition Facility and the Laser Megajoule will be tested at Lawrence Livermore National Laboratory. The prototype amplifier, which is an ensemble of modules from LLNL and Centre d'Etudes de Limeil-Valenton, is cassette-based with bottom access for maintenance. A sealed maintenance transfer vehicle which moves optical cassettes between the amplifier and the assembly cleanroom, and a vacuum gripper which holds laser slabs during cassette assembly will also be tested. The prototype amplifier will be used to verify amplifier optical performance, thermal recovery time, and cleanliness of mechanical operations

  15. HIGH AVERAGE POWER OPTICAL FEL AMPLIFIERS

    International Nuclear Information System (INIS)

    2005-01-01

    Historically, the first demonstration of the optical FEL was in an amplifier configuration at Stanford University [l]. There were other notable instances of amplifying a seed laser, such as the LLNL PALADIN amplifier [2] and the BNL ATF High-Gain Harmonic Generation FEL [3]. However, for the most part FELs are operated as oscillators or self amplified spontaneous emission devices. Yet, in wavelength regimes where a conventional laser seed can be used, the FEL can be used as an amplifier. One promising application is for very high average power generation, for instance FEL's with average power of 100 kW or more. The high electron beam power, high brightness and high efficiency that can be achieved with photoinjectors and superconducting Energy Recovery Linacs (ERL) combine well with the high-gain FEL amplifier to produce unprecedented average power FELs. This combination has a number of advantages. In particular, we show that for a given FEL power, an FEL amplifier can introduce lower energy spread in the beam as compared to a traditional oscillator. This properly gives the ERL based FEL amplifier a great wall-plug to optical power efficiency advantage. The optics for an amplifier is simple and compact. In addition to the general features of the high average power FEL amplifier, we will look at a 100 kW class FEL amplifier is being designed to operate on the 0.5 ampere Energy Recovery Linac which is under construction at Brookhaven National Laboratory's Collider-Accelerator Department

  16. Audio power amplifier design handbook

    CERN Document Server

    Self, Douglas

    2013-01-01

    This book is essential for audio power amplifier designers and engineers for one simple reason...it enables you as a professional to develop reliable, high-performance circuits. The Author Douglas Self covers the major issues of distortion and linearity, power supplies, overload, DC-protection and reactive loading. He also tackles unusual forms of compensation and distortion produced by capacitors and fuses. This completely updated fifth edition includes four NEW chapters including one on The XD Principle, invented by the author, and used by Cambridge Audio. Cro

  17. Cathode-follower power amplifier

    International Nuclear Information System (INIS)

    Giordano, S.; Puglisi, M.

    1983-01-01

    In circular accelerators and particularly in storage rings it is essential that the total impedance, as seen by the beam, be kept below some critical value. A model of the accelerating system was built using a single-ended cathode-follower amplifier driving a ferrite-loaded cavity. The system operated at 234.5 kHz with a peak output voltage of +-10 kV on the gap. The dynamic output impedance, as measured on the gap, was < 15 ohms

  18. Propagation delay of femtosecond pulses in an optical amplifier

    DEFF Research Database (Denmark)

    Poel, Mike van der; Mørk, Jesper; Hvam, Jørn Märcher

    of 2.6 THz, through a quantum-dot (QD) semiconductor amplifier (SOA) at room temperature. This extremely large bandwidth, on the other hand, is at the cost of a rather small group index change of ?ng=4*10-3. We have performed two types of femtosecond pulse slow-down and advancement experiments....... In the first experiment, we prepare a narrow peak or dip in the SOA gain spectrum by injection of a strong pump pulse4. The resulting dispersion feature is then probed by a weak pulse. In the second experiment, we measure self-slowdown or advancement as pulse energy isincreased5. In both cases, we perform...

  19. Linearizing of Low Noise Power Amplifier Using 5.8GHz Double Loop Feedforward Linearization Technique

    Directory of Open Access Journals (Sweden)

    Abdulkareem Mokif Obais

    2017-05-01

    Full Text Available In this paper, a double loop feedforward linearization technique is analyzed and built with a MMIC low noise amplifier “HMC753” as main amplifier and a two-stage class-A power amplifier as error amplifier. The system is operated with 5V DC supply at a center frequency of 5.8GHz and a bandwidth of 500MHz. The proposed technique, increases the linearity of the MMIC amplifier from 18dBm at 1dB compression point to more than 26dBm. In addition, the proposed system is tested with OFDM signal and it reveals good response in maximizing the linearity region and eliminating distortions. The proposed system is designed and simulated onAdvanced Wave Research-Microwave Office (AWR-MWO.

  20. A system for biasing a differential amplifier

    International Nuclear Information System (INIS)

    Barbier, Daniel; Ittel, J.M.; Poujois, Robert

    1975-01-01

    This invention concerns a system for biasing a differential amplifier. It particularly applies to the integrated differential amplifiers designed with MOS field effect transistors. Variations in the technological parameters may well cause the amplifying transistors to work outside their usual operational area, in other words outside the linear part of the transfer characteristic. To ensure that these transistors function correctly, it is necessary that the value of the voltage difference at the output be equally null. To do this and to centre on the so called 'rest' point of the amplifier transfer charateristic, the condition will be set that the output potentials of each amplifier transistor should have a zero value or a constant value as sum. With this in view, the bias on the source (generally a transistor powered by its grid bias voltage) supplying current to the two amplifying transistors fitted in parallel, is permanently adjusted in a suitable manner [fr

  1. A New Principle for a High Efficiency Power Audio Amplifier for Use with a Digital Preamplifier

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt

    1986-01-01

    The use of class-B and class-D amlifiers for converting digital audio signals to analog signals is discussed. It is shown that the class-D amplifier is unsuitable due to distortion. Therefore, a new principle involving a switch-mode power supply and a class-B amplifier is suggested. By regulating...... the supply voltage to the amplifier according to the amplitude of the audio signal, a higher efficiency than can be obtained by the current principles is achieved. The regulation can be done very efficiently by generating the control signal to the power supply in advance of the audio signal, made possible...

  2. Enhanced Gain in Photonic Crystal Amplifiers

    DEFF Research Database (Denmark)

    Ek, Sara; Semenova, Elizaveta; Hansen, Per Lunnemann

    2012-01-01

    We experimentally demonstrate enhanced gain in the slow-light regime of quantum well photonic crystal amplifiers. A strong gain enhancement is observed with the increase of the group refractive index, due to light slow-down. The slow light enhancement is shown in a amplified spontaneous emission....... These results are promising for short and efficient semiconductor optical amplifiers. This effect will also benefit other devices, such as mode locked lasers....

  3. Very broad bandwidth klystron amplifiers

    Science.gov (United States)

    Faillon, G.; Egloff, G.; Farvet, C.

    Large surveillance radars use transmitters at peak power levels of around one MW and average levels of a few kW, and possibly several tens of kW, in S band, or even C band. In general, the amplification stage of these transmitters is a microwave power tube, frequently a klystron. Although designers often turn to klystrons because of their good peak and average power capabilities, they still see them as narrow band amplifiers, undoubtedly because of their resonant cavities which, at first sight, would seem highly selective. But, with the progress of recent years, it has now become quite feasible to use these tubes in installations requiring bandwidths in excess of 10 - 12 percent, and even 15 percent, at 1 MW peak for example, in S-band.

  4. Hydraulically amplified PZT mems actuator

    Science.gov (United States)

    Miles, Robin R.

    2004-11-02

    A hydraulically amplified microelectromechanical systems actuator. A piece of piezoelectric material or stacked piezo bimorph is bonded or deposited as a thin film. The piece is operatively connected to a primary membrane. A reservoir is operatively connected to the primary membrane. The reservoir contains a fluid. A membrane is operatively connected to the reservoir. In operation, energizing the piezoelectric material causing the piezoelectric material to bow. Bowing of the piezoelectric material causes movement of the primary membrane. Movement of the primary membrane results in a force in being transmitted to the liquid in the reservoir. The force in the liquid causes movement of the membrane. Movement of the membrane results in an operating actuator.

  5. Transverse pumped laser amplifier architecture

    Science.gov (United States)

    Bayramian, Andrew James; Manes, Kenneth; Deri, Robert; Erlandson, Al; Caird, John; Spaeth, Mary

    2013-07-09

    An optical gain architecture includes a pump source and a pump aperture. The architecture also includes a gain region including a gain element operable to amplify light at a laser wavelength. The gain region is characterized by a first side intersecting an optical path, a second side opposing the first side, a third side adjacent the first and second sides, and a fourth side opposing the third side. The architecture further includes a dichroic section disposed between the pump aperture and the first side of the gain region. The dichroic section is characterized by low reflectance at a pump wavelength and high reflectance at the laser wavelength. The architecture additionally includes a first cladding section proximate to the third side of the gain region and a second cladding section proximate to the fourth side of the gain region.

  6. Design of an 1800nm Raman amplifier

    DEFF Research Database (Denmark)

    Svane, Ask Sebastian; Rottwitt, Karsten

    2013-01-01

    We present the experimental results for a Raman amplifier that operates at 1810 nm and is pumped by a Raman fiber laser at 1680 nm. Both the pump laser and the Raman amplifier is polarization maintaining. A challenge when scaling Raman amplifiers to longer wavelengths is the increase...... in transmission loss, but also the reduction in the Raman gain coefficient as the amplifier wavelength is increased. Both polarization components of the Raman gain is characterized, initially for linearly co-polarized signal and pump, subsequently linearly polarized orthogonal signal and pump. The noise...

  7. Reflection amplifiers in self-regulated learning

    NARCIS (Netherlands)

    Verpoorten, Dominique

    2012-01-01

    Verpoorten, D. (2012). Reflection amplifiers in self-regulated learning. Doctoral thesis. November, 9, 2012, Heerlen, The Netherlands: Open Universiteit (CELSTEC). Datawyse / Universitaire Pers Maastricht.

  8. A new principle for a high-efficiency power audio amplifier for use with a digital preamplifier

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt

    1987-01-01

    The use of class-B and class-D amplifiers for converting digital audio signals to analog signals is discussed. It is shown that the class-D amplifier is unsuitable due to distortion. Therefore a new principle involving a switch-mode power supply and a class-B amplifier is suggested. By regulating...... the supply voltage to the amplifier according to the amplitude of the audio signal, a higher efficiency than can be obtained by the usual principles is achieved. The regulation can be done very efficiently by generating the control signal to the power supply in advance of the audio signal, made possible...

  9. Distributed feedback laser amplifiers combining the functions of amplifiers and channel filters

    DEFF Research Database (Denmark)

    Wang, Z.; Durhuus, T.; Mikkelsen, Benny

    1994-01-01

    A dynamic model for distributed feedback amplifiers, including the mode coupled equations and the carrier rate equation, is established. The presented mode coupled equations have taken into account the interaction between fast changing optical signal and the waveguide with corrugations. By showin...... the possibility of amplifying 100 ps pulses without pulse broadening, we anticipate that a distributed feedback amplifier can be used as a combined amplifier and channel filter in high bit rate transmission systems....

  10. Self-pulsation in Raman fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, Martin Erland Vestergaard; Ott, Johan Raunkjær; Rottwitt, Karsten

    2009-01-01

    Dynamic behavior caused by Brillouin scattering in Raman fiber amplifiers is studied. Modes of self-pulsation steady state oscillations are found. Their dependence on amplification scheme is demonstrated.......Dynamic behavior caused by Brillouin scattering in Raman fiber amplifiers is studied. Modes of self-pulsation steady state oscillations are found. Their dependence on amplification scheme is demonstrated....

  11. Pulse amplifier with high 'common mode rejection'

    International Nuclear Information System (INIS)

    Ijlst, P.

    1987-01-01

    The input signal of a pulse amplifier contains large 'common-mode' signals which have to be suppressed. A transformer, especially constructed for this purpose, is described. It has been tried to optimize the signal to noise ratio of the pulse amplifier by means of noise analysis. (Auth.)

  12. BROADBAND TRAVELLING WAVE SEMICONDUCTOR OPTICAL AMPLIFIER

    DEFF Research Database (Denmark)

    2010-01-01

    Broadband travelling wave semiconductor optical amplifier (100, 200, 300, 400, 800) for amplification of light, wherein the amplifier (100, 200, 300, 400, 800) comprises a waveguide region (101, 201, 301, 401, 801) for providing confinement of the light in transverse directions and adapted...

  13. Bevalac injector final stage RF amplifier upgrades

    International Nuclear Information System (INIS)

    Howard, D.; Calvert, J.; Dwinell, R.; Lax, J.; Lindner, A.; Richter, R.; Ridgeway, W.

    1991-01-01

    With the assistance of the DOE In-house Energy Management Program, the Bevalac injector final stage RF amplifier systems have been successfully upgraded to reduce energy consumption and operating costs. This recently completed project removed the energy-inefficient plate voltage modulator circuits that were used in conjunction with the final stage RF amplifiers. Construction, design, and operating parameters are described in detail

  14. Method for reducing snap in magnetic amplifiers

    Science.gov (United States)

    Fischer, R. L. E.; Word, J. L.

    1968-01-01

    Method of reducing snap in magnetic amplifiers uses a degenerative feedback circuit consisting of a resistor and a separate winding on a magnetic core. The feedback circuit extends amplifier range by allowing it to be used at lower values of output current.

  15. A fluidic/pneumatic interface amplifier

    Science.gov (United States)

    Limbert, D. E.; Kegel, T. M.

    The development of a low cost, reliable, linear pressure amplifier to interface Laminar Proportional Amplifiers (LPA) to pneumatic controllers is presented. The amplifier consists of an LPA input stage and an output stage consisting of a venturi in series with a bellows nozzle valve. The LPA output drives the bellows nozzle valve thereby altering the flowrate through the venturi. The pressure within the venturi throat region, which is the amplifier output, changes with the flowrate. Non-linear characteristics, due to supersonic flow within the venturi, are altered through the use of feedback to the LPA input. A computer based model, to aid in optimizing the amplifier design, is developed. This model incorporates the effects of shock waves and boundary layers within the venturi. Good correspondence between the model and an experimental prototype is shown.

  16. Amplified OTDR Systems for Multipoint Corrosion Monitoring

    Science.gov (United States)

    Nascimento, Jehan F.; Silva, Marcionilo J.; Coêlho, Isnaldo J. S.; Cipriano, Eliel; Martins-Filho, Joaquim F.

    2012-01-01

    We present two configurations of an amplified fiber-optic-based corrosion sensor using the optical time domain reflectometry (OTDR) technique as the interrogation method. The sensor system is multipoint, self-referenced, has no moving parts and can measure the corrosion rate several kilometers away from the OTDR equipment. The first OTDR monitoring system employs a remotely pumped in-line EDFA and it is used to evaluate the increase in system reach compared to a non-amplified configuration. The other amplified monitoring system uses an EDFA in booster configuration and we perform corrosion measurements and evaluations of system sensitivity to amplifier gain variations. Our experimental results obtained under controlled laboratory conditions show the advantages of the amplified system in terms of longer system reach with better spatial resolution, and also that the corrosion measurements obtained from our system are not sensitive to 3 dB gain variations. PMID:22737017

  17. An Implantable CMOS Amplifier for Nerve Signals

    DEFF Research Database (Denmark)

    Nielsen, Jannik Hammel; Lehmann, Torsten

    2001-01-01

    In this paper, a low noise high gain CMOS amplifier for minute nerve signals is presented. By using a mixture of weak- and strong inversion transistors, optimal noise suppression in the amplifier is achieved. A continuous-time offset-compensation technique is utilized in order to minimize impact...... on the amplifier input nodes. The method for signal recovery from noisy nerve signals is presented. A prototype amplifier is realized in a standard digital 0.5 μm CMOS single poly, n-well process. The prototype amplifier features a gain of 80 dB over a 3.6 kHz bandwidth, a CMRR of more than 87 dB and a PSRR...

  18. Bandwidth tunable amplifier for recording biopotential signals.

    Science.gov (United States)

    Hwang, Sungkil; Aninakwa, Kofi; Sonkusale, Sameer

    2010-01-01

    This paper presents a low noise, low power, bandwidth tunable amplifier for bio-potential signal recording applications. By employing depletion-mode pMOS transistor in diode configuration as a tunable sub pA current source to adjust the resistivity of MOS-Bipolar pseudo-resistor, the bandwidth is adjusted without any need for a separate band-pass filter stage. For high CMRR, PSRR and dynamic range, a fully differential structure is used in the design of the amplifier. The amplifier achieves a midband gain of 39.8dB with a tunable high-pass cutoff frequency ranging from 0.1Hz to 300Hz. The amplifier is fabricated in 0.18εm CMOS process and occupies 0.14mm(2) of chip area. A three electrode ECG measurement is performed using the proposed amplifier to show its feasibility for low power, compact wearable ECG monitoring application.

  19. Dual-range linearized transimpedance amplifier system

    Science.gov (United States)

    Wessendorf, Kurt O.

    2010-11-02

    A transimpedance amplifier system is disclosed which simultaneously generates a low-gain output signal and a high-gain output signal from an input current signal using a single transimpedance amplifier having two different feedback loops with different amplification factors to generate two different output voltage signals. One of the feedback loops includes a resistor, and the other feedback loop includes another resistor in series with one or more diodes. The transimpedance amplifier system includes a signal linearizer to linearize one or both of the low- and high-gain output signals by scaling and adding the two output voltage signals from the transimpedance amplifier. The signal linearizer can be formed either as an analog device using one or two summing amplifiers, or alternately can be formed as a digital device using two analog-to-digital converters and a digital signal processor (e.g. a microprocessor or a computer).

  20. Detection of Non-Amplified Genomic DNA

    CERN Document Server

    Corradini, Roberto

    2012-01-01

    This book offers a state-of-the-art overview on non amplified DNA detection methods and provides chemists, biochemists, biotechnologists and material scientists with an introduction to these methods. In fact all these fields have dedicated resources to the problem of nucleic acid detection, each contributing with their own specific methods and concepts. This book will explain the basic principles of the different non amplified DNA detection methods available, highlighting their respective advantages and limitations. The importance of non-amplified DNA sequencing technologies will be also discussed. Non-amplified DNA detection can be achieved by adopting different techniques. Such techniques have allowed the commercialization of innovative platforms for DNA detection that are expected to break into the DNA diagnostics market. The enhanced sensitivity required for the detection of non amplified genomic DNA has prompted new strategies that can achieve ultrasensitivity by combining specific materials with specifi...

  1. Ultrafast disk lasers and amplifiers

    Science.gov (United States)

    Sutter, Dirk H.; Kleinbauer, Jochen; Bauer, Dominik; Wolf, Martin; Tan, Chuong; Gebs, Raphael; Budnicki, Aleksander; Wagenblast, Philipp; Weiler, Sascha

    2012-03-01

    Disk lasers with multi-kW continuous wave (CW) output power are widely used in manufacturing, primarily for cutting and welding applications, notably in the automotive industry. The ytterbium disk technology combines high power (average and/or peak power), excellent beam quality, high efficiency, and high reliability with low investment and operating costs. Fundamental mode picosecond disk lasers are well established in micro machining at high throughput and perfect precision. Following the world's first market introduction of industrial grade 50 W picosecond lasers (TruMicro 5050) at the Photonics West 2008, the second generation of the TruMicro series 5000 now provides twice the average power (100 W at 1030 nm, or 60 W frequency doubled, green output) at a significantly reduced footprint. Mode-locked disk oscillators achieve by far the highest average power of any unamplified lasers, significantly exceeding the 100 W level in laboratory set-ups. With robust long resonators their multi-microjoule pulse energies begin to compete with typical ultrafast amplifiers. In addition, significant interest in disk technology has recently come from the extreme light laser community, aiming for ultra-high peak powers of petawatts and beyond.

  2. Nonlinearly driven oscillations in the gyrotron traveling-wave amplifier

    International Nuclear Information System (INIS)

    Chiu, C. C.; Pao, K. F.; Yan, Y. C.; Chu, K. R.; Barnett, L. R.; Luhmann, N. C. Jr.

    2008-01-01

    By delivering unprecedented power and gain, the gyrotron traveling-wave amplifier (gyro-TWT) offers great promise for advanced millimeter wave radars. However, the underlying physics of this complex nonlinear system is yet to be fully elucidated. Here, we report a new phenomenon in the form of nonlinearly driven oscillations. A zero-drive stable gyro-TWT is shown to be susceptible to a considerably reduced dynamic range at the band edge, followed by a sudden transition into driven oscillations and then a hysteresis effect. An analysis of this unexpected behavior and its physical interpretation are presented.

  3. Amplify-and-forward relaying in wireless communications

    CERN Document Server

    Rodriguez, Leonardo Jimenez; Le-Ngoc, Tho

    2015-01-01

    This SpringerBrief explores the advantage of relaying techniques in addressing the increasing demand for high data rates and reliable services over the air. It demonstrates how to design cost-effective relay systems that provide high spectral efficiency and fully exploit the diversity of the relay channel. The brief covers advances in achievable rates, power allocation schemes, and error performance for half-duplex (HD) and full-duplex (FD) amplify-and-forward (AF) single-relay systems. The authors discuss the capacity and respective optimal power allocation for a wide range of HD protocols ov

  4. Localization of the cochlear amplifier in living sensitive ears.

    Directory of Open Access Journals (Sweden)

    Tianying Ren

    Full Text Available BACKGROUND: To detect soft sounds, the mammalian cochlea increases its sensitivity by amplifying incoming sounds up to one thousand times. Although the cochlear amplifier is thought to be a local cellular process at an area basal to the response peak on the spiral basilar membrane, its location has not been demonstrated experimentally. METHODOLOGY AND PRINCIPAL FINDINGS: Using a sensitive laser interferometer to measure sub-nanometer vibrations at two locations along the basilar membrane in sensitive gerbil cochleae, here we show that the cochlea can boost soft sound-induced vibrations as much as 50 dB/mm at an area proximal to the response peak on the basilar membrane. The observed amplification works maximally at low sound levels and at frequencies immediately below the peak-response frequency of the measured apical location. The amplification decreases more than 65 dB/mm as sound levels increases. CONCLUSIONS AND SIGNIFICANCE: We conclude that the cochlea amplifier resides at a small longitudinal region basal to the response peak in the sensitive cochlea. These data provides critical information for advancing our knowledge on cochlear mechanisms responsible for the remarkable hearing sensitivity, frequency selectivity and dynamic range.

  5. Phase noise in RF and microwave amplifiers.

    Science.gov (United States)

    Boudot, Rodolphe; Rubiola, Enrico

    2012-12-01

    Understanding amplifier phase noise is a critical issue in many fields of engineering and physics, such as oscillators, frequency synthesis, telecommunication, radar, and spectroscopy; in the emerging domain of microwave photonics; and in exotic fields, such as radio astronomy, particle accelerators, etc. Focusing on the two main types of base noise in amplifiers, white and flicker, the power spectral density of the random phase φ(t) is Sφ(f) = b(0) + b(-1)/f. White phase noise results from adding white noise to the RF spectrum in the carrier region. For a given RF noise level, b(0) is proportional to the reciprocal of the carrier power P(0). By contrast, flicker results from a near-dc 1/f noise-present in all electronic devices-which modulates the carrier through some parametric effect in the semiconductor. Thus, b(-1) is a parameter of the amplifier, constant in a wide range of P(0). The consequences are the following: Connecting m equal amplifiers in parallel, b(-1) is 1/m times that of one device. Cascading m equal amplifiers, b(-1) is m times that of one amplifier. Recirculating the signal in an amplifier so that the gain increases by a power of m (a factor of m in decibels) as a result of positive feedback (regeneration), we find that b(-1) is m(2) times that of the amplifier alone. The feedforward amplifier exhibits extremely low b(-1) because the carrier is ideally nulled at the input of its internal error amplifier. Starting with an extensive review of the literature, this article introduces a system-oriented model which describes the phase flickering. Several amplifier architectures (cascaded, parallel, etc.) are analyzed systematically, deriving the phase noise from the general model. There follow numerous measurements of amplifiers using different technologies, including some old samples, and in a wide frequency range (HF to microwaves), which validate the theory. In turn, theory and results provide design guidelines and give suggestions for CAD and

  6. Simulations of longitudinally pumped dye laser amplifier

    International Nuclear Information System (INIS)

    Takehisa, Kiwamu; Takemori, Satoshi

    1995-01-01

    Simulations of a copper laser pumped dye laser amplifier and new designs of the longitudinally pumped dye laser amplifier are presented. The simulations take the consideration of the amplified spontaneous emission (ASE). The new designs utilize a center-hole reflector instead of a dichroic mirror. The simulation results indicate that the poor spatial overlap between the pump beam and the dye beam in the transverse pumping not only reduces the laser output power, but also generates ASE strongly. The results also indicate that the longitudinal pumping is as efficient as the transverse pumping. (author)

  7. A parallel input composite transimpedance amplifier

    Science.gov (United States)

    Kim, D. J.; Kim, C.

    2018-01-01

    A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

  8. Fundamentals of RF and microwave transistor amplifiers

    CERN Document Server

    Bahl, Inder J

    2009-01-01

    A Comprehensive and Up-to-Date Treatment of RF and Microwave Transistor Amplifiers This book provides state-of-the-art coverage of RF and microwave transistor amplifiers, including low-noise, narrowband, broadband, linear, high-power, high-efficiency, and high-voltage. Topics covered include modeling, analysis, design, packaging, and thermal and fabrication considerations. Through a unique integration of theory and practice, readers will learn to solve amplifier-related design problems ranging from matching networks to biasing and stability. More than 240 problems are included to help read

  9. Quantum electronics maser amplifiers and oscillators

    CERN Document Server

    Fain, V M; Sanders, J H

    2013-01-01

    Quantum Electronics, Volume 2: Maser Amplifiers and Oscillators deals with the experimental and theoretical aspects of maser amplifiers and oscillators which are based on the principles of quantum electronics. It shows how the concepts and equations used in quantum electronics follow from the basic principles of theoretical physics.Comprised of three chapters, this volume begins with a discussion on the elements of the theory of quantum oscillators and amplifiers working in the microwave region, along with the practical achievements in this field. Attention is paid to two-level paramagnetic ma

  10. Unconditionally stable microwave Si-IMPATT amplifiers

    International Nuclear Information System (INIS)

    Seddik, M.M.

    1986-07-01

    The purpose of this investigation has been the development of an improved understanding of the design and analysis of microwave reflection amplifiers employing the negative resistance property of the IMPATT devices. Unconditionally stable amplifier circuit using a Silicon IMPATT diode is designed. The problems associated with the design procedures and the stability criterion are discussed. A computer program is developed to perform the computations. The stable characteristics of a reflection-type Si-IMPATT amplifier, such as gain, frequency and bandwidth are examined. It was found that at large signal drive levels, 7 dB gain with bandwidth of 800 MHz at 22,5 mA was obtained. (author)

  11. Automatic error compensation in dc amplifiers

    International Nuclear Information System (INIS)

    Longden, L.L.

    1976-01-01

    When operational amplifiers are exposed to high levels of neutron fluence or total ionizing dose, significant changes may be observed in input voltages and currents. These changes may produce large errors at the output of direct-coupled amplifier stages. Therefore, the need exists for automatic compensation techniques. However, previously introduced techniques compensate only for errors in the main amplifier and neglect the errors induced by the compensating circuitry. In this paper, the techniques introduced compensate not only for errors in the main operational amplifier, but also for errors induced by the compensation circuitry. Included in the paper is a theoretical analysis of each compensation technique, along with advantages and disadvantages of each. Important design criteria and information necessary for proper selection of semiconductor switches will also be included. Introduced in this paper will be compensation circuitry for both resistive and capacitive feedback networks

  12. Stimulated Brillouin scattering threshold in fiber amplifiers

    International Nuclear Information System (INIS)

    Liang Liping; Chang Liping

    2011-01-01

    Based on the wave coupling theory and the evolution model of the critical pump power (or Brillouin threshold) for stimulated Brillouin scattering (SBS) in double-clad fiber amplifiers, the influence of signal bandwidth, fiber-core diameter and amplifier gain on SBS threshold is simulated theoretically. And experimental measurements of SBS are presented in ytterbium-doped double-clad fiber amplifiers with single-frequency hundred nanosecond pulse amplification. Under different input signal pulses, the forward amplified pulse distortion is observed when the pulse energy is up to 660 nJ and the peak power is up to 3.3 W in the pulse amplification with pulse duration of 200 ns and repetition rate of 1 Hz. And the backward SBS narrow pulse appears. The pulse peak power equals to SBS threshold. Good agreement is shown between the modeled and experimental data. (authors)

  13. Complementary DNA-amplified fragment length polymorphism ...

    African Journals Online (AJOL)

    Complementary DNA-amplified fragment length polymorphism (AFLP-cDNA) analysis of differential gene expression from the xerophyte Ammopiptanthus mongolicus in response to cold, drought and cold together with drought.

  14. Behavior of MOSFET Amplifier in Radiation Fields

    International Nuclear Information System (INIS)

    Sharshar, K.A.A.; Ashry, M.

    2000-01-01

    MOSFET type 2 N 3823 characteristics and its application as an amplifier are analyzed including the effects of gamma, electron beam 1.5 MeV 25 m A and neutron flux. The 1-V characteristics, transfer curve, and the frequency response of the amplifier, and the amplification factor(A v 0 are discussed with MOSFET circuit parameters. The drain current and the amplitude of the output signal decrease as the absorbed dose increases. The measured values of the amplified signal are attenuated by 30% and 6% after exposing the MOSFET to gamma radiation and electron beam at the same dose respectively. Also for exposure to 4x10 13 N/cm 3 neutrons decreased the measured value of the amplified signal by 73% of the initial values. The decrease in the gain of the MOSFET is due to the degradation of the transconductance. It is also noticed that percentage of the decrease depends on the type of radiation

  15. Quantum-Limited Directional Amplifiers with Optomechanics

    Science.gov (United States)

    Malz, Daniel; Tóth, László D.; Bernier, Nathan R.; Feofanov, Alexey K.; Kippenberg, Tobias J.; Nunnenkamp, Andreas

    2018-01-01

    Directional amplifiers are an important resource in quantum-information processing, as they protect sensitive quantum systems from excess noise. Here, we propose an implementation of phase-preserving and phase-sensitive directional amplifiers for microwave signals in an electromechanical setup comprising two microwave cavities and two mechanical resonators. We show that both can reach their respective quantum limits on added noise. In the reverse direction, they emit thermal noise stemming from the mechanical resonators; we discuss how this noise can be suppressed, a crucial aspect for technological applications. The isolation bandwidth in both is of the order of the mechanical linewidth divided by the amplitude gain. We derive the bandwidth and gain-bandwidth product for both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth product. Our study represents an important step toward flexible, on-chip integrated nonreciprocal amplifiers of microwave signals.

  16. Manhattan equation for the operational amplifier

    OpenAIRE

    Mishonov, Todor M.; Danchev, Victor I.; Petkov, Emil G.; Gourev, Vassil N.; Dimitrova, Iglika M.; Varonov, Albert M.

    2018-01-01

    A differential equation relating the voltage at the output of an operational amplifier $U_0$ and the difference between the input voltages ($U_{+}$ and $U_{-}$) has been derived. The crossover frequency $f_0$ is a parameter in this operational amplifier master equation. The formulas derived as a consequence of this equation find applications in thousands of specifications for electronic devices but as far as we know, the equation has never been published. Actually, the master equation of oper...

  17. Distributed amplifier using Josephson vortex flow transistors

    International Nuclear Information System (INIS)

    McGinnis, D.P.; Beyer, J.B.; Nordman, J.E.

    1986-01-01

    A wide-band traveling wave amplifier using vortex flow transistors is proposed. A vortex flow transistor is a long Josephson junction used as a current controlled voltage source. The dual nature of this device to the field effect transistor is exploited. A circuit model of this device is proposed and a distributed amplifier utilizing 50 vortex flow transistors is predicted to have useful gain to 100 GHz

  18. Multiple excitation regenerative amplifier inertial confinement system

    International Nuclear Information System (INIS)

    George, V.E.; Haas, R.A.; Krupke, W.F.; Schlitt, L.G.

    1980-01-01

    The invention relates to apparatus and methods for producing high intensity laser radiation generation which is achieved through an optical amplifier-storage ring design. One or two synchronized, counterpropagating laser pulses are injected into a regenerative amplifier cavity and amplified by gain media which are pumped repetitively by electrical or optical means. The gain media excitation pulses are tailored to efficiently amplify the laser pulses during each transit. After the laser pulses have been amplified to the desired intensity level, they are either switched out of the cavity by some switch means, as for example an electro-optical device, for any well known laser end uses, or a target means may be injected into the regenerative amplifier cavity in such a way as to intercept simultaneously the counterpropagating laser pulses. One such well known end uses to which this invention is intended is for production of high density and temperature plasmas suitable for generating neutrons, ions and x-rays and for studying matter heated by high intensity laser radiation

  19. Controllable delay of ultrashort pulses in a quantum dot optical amplifier

    DEFF Research Database (Denmark)

    Poel, Mike van der; Mørk, Jesper; Hvam, Jørn Märcher

    2005-01-01

    Optical and electrical tuning of the propagation time of 170 fs pulses in a quantum dot semiconductor amplifier at room temperature is demonstrated. Both pulse slowdown and advancement is possible and we achieve fractional delays (delay divided with pulse duration) of up to 40%. The results...

  20. Transpermeance Amplifier Applied to Magnetic Bearings

    Directory of Open Access Journals (Sweden)

    Jossana Ferreira

    2017-02-01

    Full Text Available The most conventional approach of controlling magnetic forces in active magnetic bearings (AMBs is through current feedback amplifiers: transconductance. This enables the operation of the AMB to be understood in terms of a relatively simple current-based model as has been widely reported on in the literature. The alternative notion of using transpermeance amplifiers, which approximate the feedback of gap flux rather than current, has been in commercial use in some form for at least thirty years, however is only recently seeing more widespread acceptance as a commercial standard. This study explores how such alternative amplifiers should be modeled and then examines the differences in behavior between AMBs equipped with transconductance and transpermeance amplifiers. The focus of this study is on two aspects. The first is the influence of rotor displacement on AMB force, commonly modeled as a constant negative equivalent mechanical stiffness, and it is shown that either scheme actually leads to a finite bandwidth effect, but that this bandwidth is much lower when transpermeance is employed. The second aspect is the influence of eddy currents. Using a very simple model of eddy currents (a secondary short-circuited coil, it is demonstrated that transpermeance amplifiers can recover significant actuator bandwidth compared with transconductance, but at the cost of needing increased peak current headroom.

  1. Wideband Low Noise Amplifiers Exploiting Thermal Noise Cancellation

    NARCIS (Netherlands)

    Bruccoleri, F.; Klumperink, Eric A.M.; Nauta, Bram

    2005-01-01

    Low Noise Amplifiers (LNAs) are commonly used to amplify signals that are too weak for direct processing for example in radio or cable receivers. Traditionally, low noise amplifiers are implemented via tuned amplifiers, exploiting inductors and capacitors in resonating LC-circuits. This can render

  2. Solid-state disk amplifiers for fusion-laser systems

    Energy Technology Data Exchange (ETDEWEB)

    Martin, W.E.; Trenholme, J.B.; Linford, G.J.; Yarema, S.M.; Hurley, C.A.

    1981-09-01

    We review the design, performance, and operation of large-aperture (10 to 46 cm) solid-state disk amplifiers for use in laser systems. We present design data, prototype tests, simulations, and projections for conventional cylindrical pump-geometry amplifiers and rectangular pump-geometry disk amplifiers. The design of amplifiers for the Nova laser system is discussed.

  3. The design of high performance weak current integrated amplifier

    International Nuclear Information System (INIS)

    Chen Guojie; Cao Hui

    2005-01-01

    A design method of high performance weak current integrated amplifier using ICL7650 operational amplifier is introduced. The operating principle of circuits and the step of improving amplifier's performance are illustrated. Finally, the experimental results are given. The amplifier has programmable measurement range of 10 -9 -10 -12 A, automatic zero-correction, accurate measurement, and good stability. (authors)

  4. Power Amplifiers in CMOS Technology: A contribution to power amplifier theory and techniques

    NARCIS (Netherlands)

    Acar, M.

    2011-01-01

    In order to meet the demands from the market on cheaper, miniaturized mobile communications devices realization of RF power amplifiers in the mainstream CMOS technology is essential. In general, CMOS Power Amplifiers (PAs) require high voltage to decrease the matching network losses and for high

  5. Design considerations for RF power amplifiers demonstrated through a GSM/EDGE power amplifier module

    NARCIS (Netherlands)

    Baltus, P.G.M.; Bezooijen, van A.; Huijsing, J.H.; Steyaert, M.; Roermund, van A.H.M.

    2002-01-01

    This paper describes the design considerations for RF power amplifiers in general, including trends in systems, linearity and efficiency, the PA environment, implementation is sues and technology. As an example a triple-band (900/1800/1900MHz) dual mode (GSMIEdge) power amplifier module is described

  6. Wideband pulse amplifiers for the NECTAr chip

    Science.gov (United States)

    Sanuy, A.; Delagnes, E.; Gascon, D.; Sieiro, X.; Bolmont, J.; Corona, P.; Feinstein, F.; Glicenstein, J.-F.; Naumann, C. L.; Nayman, P.; Ribó, M.; Tavernet, J.-P.; Toussenel, F.; Vincent, P.; Vorobiov, S.

    2012-12-01

    The NECTAr collaboration's FE option for the camera of the CTA is a 16 bits and 1-3 GS/s sampling chip based on analog memories including most of the readout functions. This works describes the input amplifiers of the NECTAr ASIC. A fully differential wideband amplifier, with voltage gain up to 20 V/V and a BW of 400 MHz. As it is impossible to design a fully differential OpAmp with an 8 GHz GBW product in a 0.35 CMOS technology, an alternative implementation based on HF linearized transconductors is explored. The output buffer is a class AB miller operational amplifier, with special non-linear current boost.

  7. Wideband pulse amplifiers for the NECTAr chip

    International Nuclear Information System (INIS)

    Sanuy, A.; Delagnes, E.; Gascon, D.; Sieiro, X.; Bolmont, J.; Corona, P.; Feinstein, F.; Glicenstein, J-F.; Naumann, C.L.; Nayman, P.; Ribó, M.

    2012-01-01

    The NECTAr collaboration's FE option for the camera of the CTA is a 16 bits and 1–3 GS/s sampling chip based on analog memories including most of the readout functions. This works describes the input amplifiers of the NECTAr ASIC. A fully differential wideband amplifier, with voltage gain up to 20 V/V and a BW of 400 MHz. As it is impossible to design a fully differential OpAmp with an 8 GHz GBW product in a 0.35 CMOS technology, an alternative implementation based on HF linearized transconductors is explored. The output buffer is a class AB miller operational amplifier, with special non-linear current boost.

  8. Wideband pulse amplifiers for the NECTAr chip

    Energy Technology Data Exchange (ETDEWEB)

    Sanuy, A., E-mail: asanuy@ecm.ub.es [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Delagnes, E. [IRFU/DSM/CEA, CE-Saclay, Bat. 141 SEN Saclay, F-91191, Gif-sur-Yvette (France); Gascon, D. [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Sieiro, X. [Departament d' Electronica, Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Bolmont, J.; Corona, P. [LPNHE, Universite Paris VI and Universite Paris VII and IN2P3/CNRS, Barre 12-22, 1er etage, 4 place Jussieu, 75252 Paris (France); Feinstein, F. [LUPM, Universite Montpellier II and IN2P3/CNRS, CC072, bat. 13, place Eugene Bataillon, 34095 Montpellier (France); Glicenstein, J-F. [IRFU/DSM/CEA, CE-Saclay, Bat. 141 SEN Saclay, F-91191, Gif-sur-Yvette (France); Naumann, C.L.; Nayman, P. [LPNHE, Universite Paris VI and Universite Paris VII and IN2P3/CNRS, Barre 12-22, 1er etage, 4 place Jussieu, 75252 Paris (France); Ribo, M. [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); and others

    2012-12-11

    The NECTAr collaboration's FE option for the camera of the CTA is a 16 bits and 1-3 GS/s sampling chip based on analog memories including most of the readout functions. This works describes the input amplifiers of the NECTAr ASIC. A fully differential wideband amplifier, with voltage gain up to 20 V/V and a BW of 400 MHz. As it is impossible to design a fully differential OpAmp with an 8 GHz GBW product in a 0.35 CMOS technology, an alternative implementation based on HF linearized transconductors is explored. The output buffer is a class AB miller operational amplifier, with special non-linear current boost.

  9. An automated test facility for neutronic amplifiers

    International Nuclear Information System (INIS)

    Beattie, W.J.

    1997-01-01

    Neutronic amplifiers are used at the Chalk River Laboratory in applications such as neutron flux monitoring and reactor control systems. Routine preventive maintenance of control and safety systems included annual calibration and characterization of the neutronic amplifiers. An investigation into the traditional methods of annual routine maintenance of amplifiers concluded that frequency and phase response measurements in particular were labour intensive and subject to non-repeatable errors. A decision was made to upgrade testing methods and facilities by using programmable test equipment under the control of a computer. In order to verify the results of the routine measurements, expressions for the transfer functions were derived from the circuit diagrams. Frequency and phase responses were then calculated and plotted thus providing a bench-mark to which the test results can be compared. (author)

  10. A high-efficiency superconductor distributed amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Q P, E-mail: quentin.herr@ngc.co [Northrop Grumman Corporation, 7323 Aviation Boulevard, Baltimore, MD 21240 (United States)

    2010-02-15

    A superconductor output amplifier that converts single-flux-quantum signals to a non-return-to-zero pattern is reported using a twelve-stage distributed amplifier configuration. The output amplitude is measured to be 1.75 mV over a wide bias current range of {+-} 12%. The bit error rate is measured using a Delta-Sigma data pattern to be less than 1 x 10{sup -9} at 10 Gb s{sup -1} per channel. Analysis of the eye diagram suggests that the actual bit error rate may be much lower. The amplifier has power efficiency of 12% neglecting the termination resistor, which may be eliminated from the circuit with a small modification. (rapid communication)

  11. Noise figure of amplified dispersive Fourier transformation

    International Nuclear Information System (INIS)

    Goda, Keisuke; Jalali, Bahram

    2010-01-01

    Amplified dispersive Fourier transformation (ADFT) is a powerful tool for fast real-time spectroscopy as it overcomes the limitations of traditional optical spectrometers. ADFT maps the spectrum of an optical pulse into a temporal waveform using group-velocity dispersion and simultaneously amplifies it in the optical domain. It greatly simplifies spectroscopy by replacing the diffraction grating and detector array in the conventional spectrometer with a dispersive fiber and single-pixel photodetector, enabling ultrafast real-time spectroscopic measurements. Following our earlier work on the theory of ADFT, here we study the effect of noise on ADFT. We derive the noise figure of ADFT and discuss its dependence on various parameters.

  12. Predistortion of a Bidirectional Cuk Audio Amplifier

    DEFF Research Database (Denmark)

    Birch, Thomas Hagen; Nielsen, Dennis; Knott, Arnold

    2014-01-01

    Some non-linear amplifier topologies are capable of providing a larger voltage gain than one from a DC source, which could make them suitable for various applications. However, the non-linearities introduce a significant amount of harmonic distortion (THD). Some of this distortion could be reduced...... using predistortion. This paper suggests linearizing a nonlinear bidirectional Cuk audio amplifier using an analog predistortion approach. A prototype power stage was built and results show that a voltage gain of up to 9 dB and reduction in THD from 6% down to 3% was obtainable using this approach....

  13. Cryogenic transimpedance amplifier for micromechanical capacitive sensors.

    Science.gov (United States)

    Antonio, D; Pastoriza, H; Julián, P; Mandolesi, P

    2008-08-01

    We developed a cryogenic transimpedance amplifier that works at a broad range of temperatures, from room temperature down to 4 K. The device was realized with a standard complementary metal oxide semiconductor 1.5 mum process. Measurements of current-voltage characteristics, open-loop gain, input referred noise current, and power consumption are presented as a function of temperature. The transimpedance amplifier has been successfully applied to sense the motion of a polysilicon micromechanical oscillator at low temperatures. The whole device is intended to serve as a magnetometer for microscopic superconducting samples.

  14. Dynamic range meter for radiofrequency amplifiers

    Directory of Open Access Journals (Sweden)

    Drozd S. S.

    2009-04-01

    Full Text Available The new measurement setup having increased on 20…30 dB the own dynamic range in comparison with the standard circuit of the dynamic range meter is offered and the rated value of an error bringing by setup in the worst case does not exceed ± 2,8 dB. The measurement setup can be applied also to determinate levels of intermodulation components average power amplifiers and powerful amplifiers of a low-frequency at replacement of the quartz filter on meeting low-frequency the LC-filter and the spectrum analyzer.

  15. Optimization of a high efficiency FEL amplifier

    International Nuclear Information System (INIS)

    Schneidmiller, E.A.; Yurkov, M.V.

    2014-10-01

    The problem of an efficiency increase of an FEL amplifier is now of great practical importance. Technique of undulator tapering in the post-saturation regime is used at the existing X-ray FELs LCLS and SACLA, and is planned for use at the European XFEL, Swiss FEL, and PAL XFEL. There are also discussions on the future of high peak and average power FELs for scientific and industrial applications. In this paper we perform detailed analysis of the tapering strategies for high power seeded FEL amplifiers. Application of similarity techniques allows us to derive universal law of the undulator tapering.

  16. Operational amplifier circuits analysis and design

    CERN Document Server

    Nelson, J C C

    1995-01-01

    This book, a revised and updated version of the author's Basic Operational Amplifiers (Butterworths 1986), enables the non-specialist to make effective use of readily available integrated circuit operational amplifiers for a range of applications, including instrumentation, signal generation and processing.It is assumed the reader has a background in the basic techniques of circuit analysis, particularly the use of j notation for reactive circuits, with a corresponding level of mathematical ability. The underlying theory is explained with sufficient but not excessive, detail. A range of compu

  17. Cavity enhanced rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    A Williamson, Lewis; J Longdell, Jevon

    2014-01-01

    Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

  18. Induction-linac based free-electron laser amplifiers for plasma heating

    International Nuclear Information System (INIS)

    Jong, R.A.

    1988-01-01

    We describe an induction-linac based free-electron laser amplifier that is presently under construction at the Lawrence Livermore National Laboratory. It is designed to produce up to 2 MW of average power at a frequency of 250 GHz for plasma heating experiments in the Microwave Tokamak Experiment. In addition, we shall describe a FEL amplifier design for plasma heating of advanced tokamak fusion devices. This system is designed to produce average power levels of about 10 MW at frequencies ranging form 280 to 560 GHz. 7 refs., 1 tab

  19. Fast and slow light property improvement in erbium-doped amplifier

    Science.gov (United States)

    Peng, P. C.; Wu, F. K.; Kao, W. C.; Chen, J.; Lin, C. T.; Chi, S.

    2013-01-01

    This work experimentally demonstrates improvement of the fast light property in erbium-doped amplifiers at room temperature. The difference between the signal power and the pump power associated with bending loss is used to control the signal power at the different positions of the erbium-doped fiber (EDF) to improve the fast light property. Periodic bending of the EDF increases the time advance of the probe signal by over 288%. Additionally, this concept also could improve the fast light property using coherent population oscillations in semiconductor optical amplifiers.

  20. Hybrid amplifier for calorimetry with photodiode readout

    Energy Technology Data Exchange (ETDEWEB)

    Sushkov, V V

    1994-12-31

    A hybrid surface mounted amplifier for the photodiode readout of the EM calorimeter has been developed. The main technical characteristics of the design are presented. The design able to math readout constraints for a high luminosity collider experiment is discussed. 10 refs., 2 tabs., 8 figs.

  1. Amplifier Design for Proportional Ionization Chambers

    Energy Technology Data Exchange (ETDEWEB)

    Baker, W. H.

    1950-08-24

    This paper presents the requirements of a nuclear amplifier of short resolving time, designed to accept pulses of widely varying amplitudes. Data are given which show that a proportional ionization chamber loaded with a 1,000-ohm resistor develops pulses of 0.5 microsecond duration and several volts amplitude. Results indicate that seven basic requirements are imposed on the amplifier when counting soft beta and gamma radiation in the presence of alpha particles, without absorbers. It should, (1) have a fast recovery time, (2) have a relatively good low frequency response, (3) accept pulses of widely varying heights without developing spurious pulsed, (4) have a limiting output stage, (5) preserve the inherently short rise time of the chamber, (6) minimize pulse integration, and (7) have sufficient gain to detect the weak pulses well below the chamber voltage at which continuous discharge takes place. The results obtained with an amplifier which meets these requirements is described. A formula is derived which indicates that redesign of the proportional ionization chamber might eliminate the need for an amplifier. This may be possible if the radioactive particles are collimated parallel to the collecting electrode.

  2. Methylation sensitive amplified polymorphism (MSAP) reveals that ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Key words: Salt stress, alkali stress, Gossypium hirsutum L., DNA methylation, methylation sensitive amplified polymorphism (MSAP). INTRODUCTION. DNA methylation is one of the key epigenetic mecha- nisms among eukaryotes that can modulate gene expression without the changes of DNA sequence.

  3. Enhanced timing channel for spectroscopy amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Ianakiev, K; Grigorov, N [Inst. for Nuclear Research and Nuclear Energy, Sofia (Bulgaria)

    1996-12-31

    Purpose of this paper is to analyze noise and timing performance of some methods of filtering in the fast channel. Implementation of RLC-filter into a semi-Gaussian amplifier allows to obtain the time resolution of 420 ns. 5 refs.

  4. Optimization of Pr3+:ZBLAN fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, B.; Miniscalco, J. W.; Quimby, R. S.

    1992-01-01

    Experimental parameters have been measured and used in a quantitative model of Pr3+-doped fluorozirconate fiber amplifiers. The optimum cutoff wavelength was determined to be 800 nm and the gain for 400 mW of pump was found to increase from 12 to 34 dB if the NA was increased from 0.15 to 0...

  5. Reducing Switching Artifacts in Chopper Amplifiers

    NARCIS (Netherlands)

    Kusuda, Y.

    2018-01-01

    This thesis describes the theory, design, and implementation of chopper operational amplifiers (op-amps) in CMOS integrated circuits (ICs). The chopping technique periodically corrects DC errors of such op-amps, so that low 1/f noise and stable, microvolt-level offset can be achieved. However,

  6. High-Performance Operational and Instrumentation Amplifiers

    NARCIS (Netherlands)

    Shahi, B.

    2015-01-01

    This thesis describes techniques to reduce the offset error in precision instrumentation and operational amplifiers. The offset error which is considered a major error source associated with gain blocks, together with other errors are reviewed. Conventional and newer approaches to remove offset and

  7. SINGLE CONVERSION ISOLATED IMPEDANCE TRANSFORMATION AMPLIFIER

    DEFF Research Database (Denmark)

    2003-01-01

    The invention relates to a switch mode power amplifier. A first and a second change-over switch are inserted between a DC voltage supply and a primary side of an isolation transformer. Two secondary windings are connected to a power output terminal. A first and a second secondary side power switc...

  8. Feedback analysis of transimpedance operational amplifier circuits

    DEFF Research Database (Denmark)

    Bruun, Erik

    1993-01-01

    The transimpedance or current feedback operational amplifier (CFB op-amp) is reviewed and compared to a conventional voltage mode op-amp using an analysis emphasizing the basic feedback characteristics of the circuit. With this approach the paradox of the constant bandwidth obtained from CFB op...

  9. Random amplified polymorphic DNA based genetic characterization ...

    African Journals Online (AJOL)

    Random amplified polymorphic DNA based genetic characterization of four important species of Bamboo, found in Raigad district, Maharashtra State, India. ... Bambusoideae are differentiated from other members of the family by the presence of petiolate blades with parallel venation and stamens are three, four, six or more, ...

  10. Molecular markers. Amplified fragment length polymorphism

    Directory of Open Access Journals (Sweden)

    Pržulj Novo

    2005-01-01

    Full Text Available Amplified Fragment Length Polymorphism molecular markers (AFLPs has been developed combining procedures of RFLPs and RAPDs molekular markers, i.e. the first step is restriction digestion of the genomic DNA that is followed by selective amplification of the restricted fragments. The advantage of the AFLP technique is that it allows rapid generation of a large number of reproducible markers. The reproducibility of AFLPs markers is assured by the use of restriction site-specific adapters and adapter-specific primers for PCR reaction. Only fragments containing the restriction site sequence plus the additional nucleotides will be amplified and the more selected nucleotides added on the primer sequence the fewer the number of fragments amplified by PCR. The amplified products are normally separated on a sequencing gel and visualized after exposure to X-ray film or by using fluorescent labeled primers. AFLP shave proven to be extremely proficient in revealing diversity at below the species level. A disadvantage of AFLP technique is that AFLPs are essentially a dominant marker system and not able to identify heterozygotes.

  11. Compensation techniques for operational amplifier bias current

    International Nuclear Information System (INIS)

    Silva, M.S.

    1981-01-01

    Two techniques are proposed for the compensation of the input current on operational amplifiers that can be used on inverting and non-inverting configurations. A qualitative analysis of temperature drift problems is made, and as a practical application, the construction of a voltage follower for high impedance measurements is presented. (Author) [pt

  12. Application of randomly amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    Jane

    2011-10-10

    Oct 10, 2011 ... and T7-010 based on functional markers according to He et al. (2007). These primers were constructed by Invitrogen GmbH,. Karlsruhe, Germany, and used to amplify the polyphenol oxidases genes. The sequences of these primers were as follows: T3-001: 5`-CCA TTA ACC CTC ACT AAA GGG ACC GTA ...

  13. Initial tests of an 11.4 GHz magnicon amplifier

    International Nuclear Information System (INIS)

    Gold, S.H.; Sullivan, C.A.; Manheimer, W.M.; Hafizi, B.

    1994-01-01

    The magnicon, a scanning beam microwave amplifier related to the gyrocon, is a possible replacement for klystron amplifiers in future high-gradient linear accelerators. The magnicon circuit consists of a multicavity deflection system followed by an output cavity. The purpose of the deflection system is to spin up the electron beam phase-coherently to high transverse momentum. In order to do this, the deflection cavities employ rotating TM 11 modes, producing a gyrating electron beam whose centroid rotates about the cavity axis in synchronism with the advance in phase of the rf modes. The output cavity employs a cyclotron resonant mechanism to extract principally the transverse beam momentum. It employs an rf mode that rotates synchronously with the deflection cavity modes, and with the entry point of the electron beam into the output cavity, making possible a highly efficient interaction. The NRL magnicon uses a 100--200 A, 500 keV beam produced by a cold-cathode diode on the NRL Long-Pulse Accelerator Facility. The first cavity is externally driven at 5.7 GHz, while the output cavity is designed to produce megawatts of power at 11.4 GHz in the TM 210 mode. In this paper, the authors present a progress report on the NRL magnicon experiment. They will discuss the procedure used to cold test and calibrate the magnicon circuit, and present initial results from experimental operations

  14. A reflexing electron microwave amplifier for rf particle accelerator applications

    International Nuclear Information System (INIS)

    Fazio, M.V.; Hoeberling, R.F.

    1988-01-01

    The evolution of rf-accelerator technology toward high-power, high-current, low-emittance beams produces an ever-increasing demand for efficient, very high power microwave power sources. The present klystron technology has performed very well but is not expected to produce reliable gigawatt peak-power units in the 1- to 10-GHz regime. Further major advancements must involve other types of sources. The reflexing-electron class of sources can produce microwave powers at the gigawatt level and has demonstrated operation from 800-MHz to 40-GHz. The pulse length appears to be limited by diode closure, and reflexing-electron devices have been operated in a repetitively pulsed mode. A design is presented for a reflexing electron microwave amplifier that is frequency and phase locked. In this design, the generated microwave power can be efficiently coupled to one or several accelerator loads. Frequency and phase-locking capability may permit parallel-source operation for higher power. The low-frequency (500-MHz to 10-GHz) operation at very high power required by present and proposed microwave particle accelerators makes an amplifier, based on reflexing electron phenomena, a candidate for the development of new accelerator power sources. (author)

  15. Multi-pass amplifier architecture for high power laser systems

    Science.gov (United States)

    Manes, Kenneth R; Spaeth, Mary L; Erlandson, Alvin C

    2014-04-01

    A main amplifier system includes a first reflector operable to receive input light through a first aperture and direct the input light along an optical path. The input light is characterized by a first polarization. The main amplifier system also includes a first polarizer operable to reflect light characterized by the first polarization state. The main amplifier system further includes a first and second set of amplifier modules. Each of the first and second set of amplifier modules includes an entrance window, a quarter wave plate, a plurality of amplifier slablets arrayed substantially parallel to each other, and an exit window. The main amplifier system additionally includes a set of mirrors operable to reflect light exiting the first set of amplifier modules to enter the second set of amplifier modules and a second polarizer operable to reflect light characterized by a second polarization state.

  16. Transmission characteristics of acoustic amplifier in thermoacoustic engine

    International Nuclear Information System (INIS)

    Sun Daming; Qiu Limin; Wang Bo; Xiao Yong

    2008-01-01

    Thermoacoustic engines are promising in practical applications for the merits of simple configuration, reliable operation and environmentally friendly working gas. An acoustic amplifier can increase the output pressure amplitude of a thermoacoustic engine (TE) and improve the matching between the engine and its load. In order to make full use of an acoustic amplifier, the transmission characteristics are studied based on linear thermoacoustic theory. Computational and experimental results show that the amplifying ability of an acoustic amplifier is mainly determined by its geometry parameters and output resistance impedance. The amplifying ability of an acoustic amplifier with appropriate length and diameter reaches its maximum when the output resistance impedance is infinite. It is also shown that the acoustic amplifier consumes an amount of acoustic power when amplifying pressure amplitude and the acoustic power consumption increases with amplifying ratio. Furthermore, a novel cascade acoustic amplifier is proposed, which has a much stronger amplifying ability with reduced acoustic power consumption. In experiments, a two-stage cascade acoustic amplifier amplifies the pressure ratio from 1.177 to 1.62 and produces a pressure amplitude of 0.547 MPa with nitrogen of 2.20 MPa as working gas. Good agreements are obtained between the theoretical analysis and experimental results. This research is instructive for comprehensively understanding the mechanism and making full use of the acoustic amplifier

  17. Is there a role for amplifiers in sexual selection?

    Science.gov (United States)

    Gualla, Filippo; Cermelli, Paolo; Castellano, Sergio

    2008-05-21

    The amplifier hypothesis states that selection could favour the evolution of traits in signallers that improve the ability of receivers to extract honest information from other signals or cues. We provide a formal definition of amplifiers based on the receiver's mechanisms of signal perception and we present a game-theoretical model in which males advertise their quality and females use sequential-sampling tactics to choose among prospective mates. The main effect of an amplifier on the female mating strategy is to increase her mating threshold, making the female more selective as the effectiveness of the amplifier increases. The effects of the amplifier on male advertising strategy depends both on the context and on the types of the amplifier involved. We consider two different contexts for the evolution of amplifiers (when the effect of amplifiers is on signals and when it is on cues) and two types of amplifiers (the 'neutral amplifier', when it improves quality assessment without altering male attractiveness, and the 'attractive amplifier', when it improves both quality assessment and male attractiveness). The game-theoretical model provides two main results. First, neutral and attractive amplifiers represent, respectively, a conditional and an unconditional signalling strategy. In fact, at the equilibrium, neutral amplifiers are displayed only by males whose advertising level lays above the female acceptance threshold, whereas attractive amplifiers are displayed by all signalling males, independent of their quality. Second, amplifiers of signals increase the differences in advertising levels between amplifying and not-amplifying males, but they decrease the differences within each group, so that the system converges towards an 'all-or-nothing' signalling strategy. By applying concepts from information theory, we show that the increase in information transfer at the perception level due to the amplifier of signals is contrasted by a decrease in information

  18. Amplified spontaneous emission spectrum and gain characteristic of a two-electrode semiconductor optical amplifier

    International Nuclear Information System (INIS)

    Wang Hanchao; Huang Lirong; Shi Zhongwei

    2011-01-01

    A two-electrode multi-quantum-well semiconductor optical amplifier is designed and fabricated. The amplified spontaneous emission (ASE) spectrum and gain were measured and analyzed. It is shown that the ASE spectrum and gain characteristic are greatly influencedby the distribution of the injection current density. By changing the injection current density of two electrodes, the full width at half maximum, peak wavelength, peak power of the ASE spectrum and the gain characteristic can be easily controlled. (semiconductor devices)

  19. Assembly and maintenance of full scale NIF amplifiers in the amplifier module prototype laboratory (AMPLAB)

    International Nuclear Information System (INIS)

    Horvath, J. A.

    1998-01-01

    Mechanical assembly and maintenance of the prototype National Ignition Facility amplifiers in the Amplifier Module Prototype Laboratory (AMPLAB) at Lawrence Livermore National Laboratory requires specialized equipment designed to manipulate large and delicate amplifier components in a safe and clean manner. Observations made during the operation of this assembly and maintenance equipment in AMPLAB provide design guidance for similar tools being built for the National Ignition Facility. Fixtures used for amplifier frame installation, laser slab and flashlamp cassette assembly, transport, and installation, and in-situ blastshield exchange are presented. Examples include a vacuum slab gripper, slab handling clean crane, slab cassette assembly fixture, sealed transport vehicle for slab cassette movement between the cleanroom and amplifier, slab cassette transfer fixture between the cleanroom and transport vehicle, and equipment needed for frame assembly unit, blastshield, an d flashlamp cassette installation and removal. The use of these tools for amplifier assembly, system reconfiguration, reflector replacement, and recovery from an abnormal occurrence such as a flashlamp explosion is described. Observations are made on the design and operation of these tools and their contribution to the final design

  20. Transport in coherently absorbing or amplifying media

    International Nuclear Information System (INIS)

    Sen, A.K.

    1995-11-01

    We study electronic transport in a one-dimensional ordered chain in the presence of either absorption or amplification at each site (the site-potential having an imaginary positive or negative part) within a single-band tightbinding Hamiltonian. The spectrum in either case for the isolated (closed) quantum system is found to become broader compared to the regular Bloch case where there is no absorption or amplification at any site. Interestingly for the transport through an infinitely long ordered chain (open quantum system), the reflectance saturates to a value greater (lesser) than unity in the amplifying (absorbing) case and the transmittance decays to zero in either case. This fact implies that the transmittance does not grow indefinitely even for an ordered, amplifying (active or lasing) medium and that it is not necessary to have any disorder or interaction induced confining mechanism on the transmitted wave, so as to achieve an amplification in the backscattered wave. (author). 8 refs, 2 figs

  1. Amplified music exposure carries risks to hearing.

    Science.gov (United States)

    da Silva, Valéria Gomes; de Oliveira, Carlos Augusto Costa Pires; Tauil, Pedro Luíz; de Castro Silva, Isabella Monteiro; Sampaio, André Luiz Lopes

    2017-02-01

    To investigate the association between changes in the outer hair cells and exposure to amplified music in a group of high-school students. In this retrospective, case-control study, 86 subjects underwent audiometry, immittance audiometry, and distortion-product otoacoustic emission tests. The subjects were questioned about their listening habits and divided into 2 groups: exposed and unexposed. Most of the subjects had reduced function in their outer hair cells, mainly beginning at 8 kHz. Among 60 subjects-30 cases and 30 controls-75% were considered exposed and 25% unexposed. The exposed subjects were 9.33 times more likely to have altered outer hair cells than the unexposed subjects were. Exposure to amplified music is associated with reduced function in the hair cells. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  2. Cryogenic cooling for high power laser amplifiers

    Directory of Open Access Journals (Sweden)

    Perin J.P.

    2013-11-01

    Full Text Available Using DPSSL (Diode Pumped Solid State Lasers as pumping technology, PW-class lasers with enhanced repetition rates are developed. Each of the Yb YAG amplifiers will be diode-pumped at a wavelength of 940 nm. This is a prerequisite for achieving high repetition rates (light amplification duration 1 millisecond and repetition rate 10 Hz. The efficiency of DPSSL is inversely proportional to the temperature, for this reason the slab amplifier have to be cooled at a temperature in the range of 100 K–170 K with a heat flux of 1 MW*m−2. This paper describes the thermo-mechanical analysis for the design of the amplification laser head, presents a preliminary proposal for the required cryogenic cooling system and finally outlines the gain of cryogenic operation for the efficiency of high pulsed laser.

  3. Spaceflight 2 um Tm Fiber MOPA Amplifier, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Fibertek proposes to design, develop, and test a spaceflight prototype 2051 nm thulium (Tm)-doped fiber amplifier (TDFA) optical master oscillator power amplifier...

  4. Conversion of the random amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    Conversion of the random amplified polymorphic DNA (RAPD) marker UBC#116 linked to Fusarium crown and root rot resistance gene (Frl) into a co-dominant sequence characterized amplified region (SCAR) marker for marker-assisted selection of tomato.

  5. Electrically Pumped Vertical-Cavity Amplifiers

    DEFF Research Database (Denmark)

    Greibe, Tine

    2007-01-01

    In this work, the design of electrically pumped vertical cavity semiconductor optical amplifiers (eVCAs) for use in a mode-locked external-cavity laser has been developed, investigated and analysed. Four different eVCAs, one top-emitting and three bottom emitting structures, have been designed...... and discussed. The thesis concludes with recommendations for further work towards the realisation of compact electrically pumped mode-locked vertical externalcavity surface emitting lasers....

  6. Self-amplifying mRNA vaccines.

    Science.gov (United States)

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Fast Electrocardiogram Amplifier Recovery after Defibrillation Shock

    Directory of Open Access Journals (Sweden)

    Ivan Dotsinsky

    2005-04-01

    Full Text Available A procedure for fast ECG amplifier recovery after defibrillation shocks was developed and simulated in the MATLAB environment. Exponentially decaying post-shock voltages have been recorded. Signals from the AHA database are taken and mixed with the recorded exponential disturbances. The algorithm applies moving averaging (comb filter on the compound input signal, thereby obtaining the samples of the disturbance. They are currently subtracted from the input signal. The results obtained show that its recovery is practically instantaneous.

  8. Ultra-low Voltage CMOS Cascode Amplifier

    OpenAIRE

    Lehmann, Torsten; Cassia, Marco

    2000-01-01

    In this paper, we design a folded cascode operational transconductance amplifier in a standard CMOS process, which has a measured 69 dB DC gain, a 2 MHz bandwidth and compatible input- and output voltage levels at a 1 V power supply. This is done by a novel Current Driven Bulk (CDB) technique, which reduces the MOST threshold voltage by forcing a constant current though the transistor bulk terminal. We also look at limitations and improvements of this CDB technique.

  9. X-ray image amplifying tube

    International Nuclear Information System (INIS)

    1977-01-01

    The photo electrons from the picture on the fluorescent input screen are amplified by an electron optical system and produce an intensified image on the output screen. This can be photographed and shown on a TV screen. The effects of stray magnetic fields are reduced by covering the input screen with a grating made of strips of ferromagnetic material such as μ metal. (T.S.E.T.)

  10. Ultra-low Voltage CMOS Cascode Amplifier

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Cassia, Marco

    2000-01-01

    In this paper, we design a folded cascode operational transconductance amplifier in a standard CMOS process, which has a measured 69 dB DC gain, a 2 MHz bandwidth and compatible input- and output voltage levels at a 1 V power supply. This is done by a novel Current Driven Bulk (CDB) technique......, which reduces the MOST threshold voltage by forcing a constant current though the transistor bulk terminal. We also look at limitations and improvements of this CDB technique....

  11. Prototype disc amplifier for Iskra-6 facility

    International Nuclear Information System (INIS)

    Grigorovich, S.V.; Eroshenko, V.F.; Krotov, V.A.; Demidov, V.L.; Kalinin, N.V.; Kurunov, R.F.; Smirnov, V.G.; Fomin, V.M.

    2006-01-01

    Eight-channel disk amplifiers of the ISKRA-6 facility are made up of sections. An amplifier section consists of eight active elements (2*4) made of KGSS-0180/35-grade neodymium phosphate glass 400*690*40 mm in size located in frames at the Brewster angle. Twenty flash-lamps are arranged in one amplifier module. The flash-lamps have an inter electrode distance of 1600 mm, the tube is 40 mm in inner diameter. The results of numerical investigations into the dynamics of high-current pulse radiation discharge are presented. The investigations were carried out by the 1-dimensional RMHD-model. This model takes into account the transient processes in the electric circuit and the physical processes in the discharge plasma: ionization, Joule heating, thermal conductivity, radiation transfer and plasma motion caused by the non-uniformity of energy introduction into the discharge in case of a non-uniform initial ionization of gas in the pumping lamp. The experimental results of spectral measurements and light efficiency of the flash-lamps depending on specific power and value of energy contribution are presented

  12. Charge sensitive amplifies. The state of arts

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kunishiro [Clear Pulse Co., Tokyo (Japan)

    1996-07-01

    In the radiation detectors, signals are essentially brought with charges produced by radiation, then it is naturally the best way to use a charge sensitive amplifier (CSA) system to extract those signals. The CSA is thought to be the best amplifier suitable to almost all the radiation detectors, if neglecting economical points of view. The CSA has been only applied to special fields like radiation detection because the concept of `charges` is not so universal against the concepts of `voltage` and `current`. The CSA, however, is low in noise and a high speed amplifier and may be applicable not only to radiation measurement but also piezoelectric devices and also bolometers. In this article, noise in the CSA, basic circuit on the CSA, concepts of `equivalent noise charge` (ENC), a method for the ENC, and importance of the `open-loop gain` in the CSA to achieve better performance of it and how to realize in a practical CSA were described. And, characteristics on a counting rate of the CSA, various circuit used in the CSA, and CSAs which are commercially available at present and special purpose CSAs were also introduced. (G.K.)

  13. Pump to signal noise transfer in parametric fiber amplifiers

    DEFF Research Database (Denmark)

    Lund-Hansen, Toke; Rottwitt, Karsten; Peucheret, Christophe

    2010-01-01

    Fiber optic parametric amplifiers have been suggested due to their potential low spontaneous emission. However, by nature the parametric amplifier only work in a forward pumped configuration, which result in transfer of relative intensity noise in the pump to the signal.......Fiber optic parametric amplifiers have been suggested due to their potential low spontaneous emission. However, by nature the parametric amplifier only work in a forward pumped configuration, which result in transfer of relative intensity noise in the pump to the signal....

  14. Noise and saturation properties of semiconductor quantum dot optical amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper

    2002-01-01

    We present a detailed theoretical analysis of quantum dot optical amplifiers. Due to the presence of a reservoir of wetting layer states, the saturation and noise properties differ markedly from bulk or QW amplifiers and may be significantly improved.......We present a detailed theoretical analysis of quantum dot optical amplifiers. Due to the presence of a reservoir of wetting layer states, the saturation and noise properties differ markedly from bulk or QW amplifiers and may be significantly improved....

  15. Differential transimpedance amplifier circuit for correlated differential amplification

    Science.gov (United States)

    Gresham, Christopher A [Albuquerque, NM; Denton, M Bonner [Tucson, AZ; Sperline, Roger P [Tucson, AZ

    2008-07-22

    A differential transimpedance amplifier circuit for correlated differential amplification. The amplifier circuit increase electronic signal-to-noise ratios in charge detection circuits designed for the detection of very small quantities of electrical charge and/or very weak electromagnetic waves. A differential, integrating capacitive transimpedance amplifier integrated circuit comprising capacitor feedback loops performs time-correlated subtraction of noise.

  16. Functional Blocks and Biquadratic ARC Filters using Transimpedance Amplifiers

    OpenAIRE

    R. Sarman; R. Prokop; T. Dostal

    1997-01-01

    The aims of the article are design and analysis of modern circuits including high performance functional blocks and biquadratic filters using transimpedance amplifiers. Here are given various types of these circuits, that works in classical voltage, current or hybrid mode. In this paper are also compared various possibilities of connection of single amplifier filters as for reduction of influence of transimpedance amplifier parasitic elements.

  17. The Dynamics of Semiconductor Optical Amplifiers – Modeling and Applications

    DEFF Research Database (Denmark)

    Mørk, Jesper; Nielsen, Mads Lønstrup; Berg, Tommy Winther

    2003-01-01

    The importance of semiconductor optical amplifiers is discussed. A semiconductor optical amplifier (SOA) is a semiconductor laser with anti-reflection coated facets that amplifies an injected light signal by means of stimulated emission. SOAs have a number of unique properties that open up...

  18. A low-voltage sense amplifier with two-stage operational amplifier clamping for flash memory

    Science.gov (United States)

    Guo, Jiarong

    2017-04-01

    A low-voltage sense amplifier with reference current generator utilizing two-stage operational amplifier clamp structure for flash memory is presented in this paper, capable of operating with minimum supply voltage at 1 V. A new reference current generation circuit composed of a reference cell and a two-stage operational amplifier clamping the drain pole of the reference cell is used to generate the reference current, which avoids the threshold limitation caused by current mirror transistor in the traditional sense amplifier. A novel reference voltage generation circuit using dummy bit-line structure without pull-down current is also adopted, which not only improves the sense window enhancing read precision but also saves power consumption. The sense amplifier was implemented in a flash realized in 90 nm flash technology. Experimental results show the access time is 14.7 ns with power supply of 1.2 V and slow corner at 125 °C. Project supported by the National Natural Science Fundation of China (No. 61376028).

  19. Note: A high dynamic range, linear response transimpedance amplifier.

    Science.gov (United States)

    Eckel, S; Sushkov, A O; Lamoreaux, S K

    2012-02-01

    We have built a high dynamic range (nine decade) transimpedance amplifier with a linear response. The amplifier uses junction-gate field effect transistors (JFETs) to switch between three different resistors in the feedback of a low input bias current operational amplifier. This allows for the creation of multiple outputs, each with a linear response and a different transimpedance gain. The overall bandwidth of the transimpedance amplifier is set by the bandwidth of the most sensitive range. For our application, we demonstrate a three-stage amplifier with transimpedance gains of approximately 10(9)Ω, 3 × 10(7)Ω, and 10(4)Ω with a bandwidth of 100 Hz.

  20. Characterization of a Common-Source Amplifier Using Ferroelectric Transistors

    Science.gov (United States)

    Hunt, Mitchell; Sayyah, Rana; MacLeond, Todd C.; Ho, Pat D.

    2010-01-01

    This paper presents empirical data that was collected through experiments using a FeFET in the established common-source amplifier circuit. The unique behavior of the FeFET lends itself to interesting and useful operation in this widely used common-source amplifier. The paper examines the effect of using a ferroelectric transistor for the amplifier. It also examines the effects of varying load resistance, biasing, and input voltages on the output signal and gives several examples of the output of the amplifier for a given input. The difference between a commonsource amplifier using a ferroelectric transistor and that using a MOSFET is addressed.

  1. Characterization of a Common-Gate Amplifier Using Ferroelectric Transistors

    Science.gov (United States)

    Hunt, Mitchell; Sayyah, Rana; MacLeod, Todd C.; Ho, Fat D.

    2011-01-01

    In this paper, the empirical data collected through experiments performed using a FeFET in the common-gate amplifier circuit is presented. The FeFET common-gate amplifier was characterized by varying all parameters in the circuit, such as load resistance, biasing of the transistor, and input voltages. Due to the polarization of the ferroelectric layer, the particular behavior of the FeFET common-gate amplifier presents interesting results. Furthermore, the differences between a FeFET common-gate amplifier and a MOSFET common-gate amplifier are examined.

  2. Class D audio amplifiers for high voltage capacitive transducers

    DEFF Research Database (Denmark)

    Nielsen, Dennis

    of high volume, weight, and cost. High efficient class D amplifiers are now widely available offering power densities, that their linear counterparts can not match. Unlike the technology of audio amplifiers, the loudspeaker is still based on the traditional electrodynamic transducer invented by C.W. Rice......Audio reproduction systems contains two key components, the amplifier and the loudspeaker. In the last 20 – 30 years the technology of audio amplifiers have performed a fundamental shift of paradigm. Class D audio amplifiers have replaced the linear amplifiers, suffering from the well-known issues...... with the low level of acoustical output power and complex amplifier requirements, have limited the commercial success of the technology. Horn or compression drivers are typically favoured, when high acoustic output power is required, this is however at the expense of significant distortion combined...

  3. Low noise amplifier for ZnS(Ag) scintillation chamber

    International Nuclear Information System (INIS)

    Do Hoang Cuong

    1998-01-01

    A new pulse amplifier that can be used with standard photomultiplier tubes coupled with Zn(Ag) scintillation chamber is presented. The amplifier based on an IC operational amplifier LF 356N consists of a low-noise charge sensitive preamplifier and pulse shaping circuits for optimization of signal to noise ratio. Temperature instability is ≤ 0.05%/ o C. Dynamic range for linear output signals is equal +7 V. The presented amplifier is used in a measuring head for 0.17 L Lucas chambers developed in Department of Nuclear Instruments and Methods of the INCT in laboratory investigations aimed to develop methods and instruments for measurement of radon concentration in the air. The amplifier can also be employed for measurement of ionizing radiation by means of other scintillators coupled to PM tube. The amplifier is followed by a pulse discriminator with adjustable discrimination level. The amplifier output signal and discriminator output pulses are fed to external devices. (author)

  4. A new semicustom integrated bipolar amplifier for silicon strip detectors

    International Nuclear Information System (INIS)

    Zimmerman, T.

    1989-01-01

    The QPA02 is a four channel DC coupled two stage transimpedance amplifier designed at Fermilab on a semicustom linear array (Quickchip 2S) manufactured by Tektronix. The chip was developed as a silicon strip amplifier but may have other applications as well. Each channel consists of a preamplifier and a second stage amplifier/sharper with differential output which can directly drive a transmission line (90 to 140 ohms). External bypass capacitors are the only discrete components required. QPA02 has been tested and demonstrated to be an effective silicon strip amplifier. Other applications may exist which can use this amplifier or a modified version of this amplifier. For example, another design is now in progress for a wire chamber amplifier, QPA03, to be reported later. Only a relatively small effort was required to modify the design and layout for this application. 11 figs

  5. High sensitivity amplifier/discriminator for PWC's

    International Nuclear Information System (INIS)

    Hansen, S.

    1983-01-01

    The facility support group at Fermilab is designing and building a general purpose beam chamber for use in several locations at the laboratory. This pwc has 128 wires per plane spaced 1 mm apart. An initial production of 25 signal planes is anticipated. In proportional chambers, the size of the signal depends exponentially on the charge stored per unit of length along the anode wire. As the wire spacing decreases, the capacitance per unit length decreases, thereby requiring increased applied voltage to restore the necessary charge per unit length. In practical terms, this phenomenon is responsible for difficulties in constructing chambers with less than 2 mm wire spacing. 1 mm chambers, therefore, are frequently operated very near to their breakdown point and/or a high gain gas containing organic compounds such as magic gas is used. This argon/iso-butane mixture has three drawbacks: it is explosive when exposed to the air, it leaves a residue on the wires after extended use and is costly. An amplifier with higher sensitivity would reduce the problems associated with operating chambers with small wire spacings and allow them to be run a safe margin below their breakdown voltage even with an inorganic gas mixture such as argon/CO2, this eliminating the need to use magic gas. Described here is a low cost amplifier with a usable threshold of less than 0.5 μA. Data on the performance of this amplifier/discriminator in operation on a prototype beam chamber are given. This data shows the advantages of the high sensitivity of this design

  6. Waveguide harmonic damper for klystron amplifier

    International Nuclear Information System (INIS)

    Kang, Y.

    1998-01-01

    A waveguide harmonic damper was designed for removing the harmonic frequency power from the klystron amplifiers of the APS linac. Straight coaxial probe antennas are used in a rectangular waveguide to form a damper. A linear array of the probe antennas is used on a narrow wall of the rectangular waveguide for damping klystron harmonics while decoupling the fundamental frequency in dominent TE 01 mode. The klystron harmonics can exist in the waveguide as waveguide higher-order modes above cutoff. Computer simulations are made to investigate the waveguide harmonic damping characteristics of the damper

  7. Active isotropic slabs: conditions for amplified reflection

    Science.gov (United States)

    Perez, Liliana I.; Matteo, Claudia L.; Etcheverry, Javier; Duplaá, María Celeste

    2012-12-01

    We analyse in detail the necessary conditions to obtain amplified reflection (AR) in isotropic interfaces when a plane wave propagates from a transparent medium towards an active one. First, we demonstrate analytically that AR is not possible if a single interface is involved. Then, we study the conditions for AR in a very simple configuration: normal incidence on an active slab immersed in transparent media. Finally, we develop an analysis in the complex plane in order to establish a geometrical method that not only describes the behaviour of active slabs but also helps to simplify the calculus.

  8. Active isotropic slabs: conditions for amplified reflection

    International Nuclear Information System (INIS)

    Perez, Liliana I; Duplaá, María Celeste; Matteo, Claudia L; Etcheverry, Javier

    2012-01-01

    We analyse in detail the necessary conditions to obtain amplified reflection (AR) in isotropic interfaces when a plane wave propagates from a transparent medium towards an active one. First, we demonstrate analytically that AR is not possible if a single interface is involved. Then, we study the conditions for AR in a very simple configuration: normal incidence on an active slab immersed in transparent media. Finally, we develop an analysis in the complex plane in order to establish a geometrical method that not only describes the behaviour of active slabs but also helps to simplify the calculus. (paper)

  9. Sm 3+-doped polymer optical waveguide amplifiers

    Science.gov (United States)

    Huang, Lihui; Tsang, Kwokchu; Pun, Edwin Yue-Bun; Xu, Shiqing

    2010-04-01

    Trivalent samarium ion (Sm 3+) doped SU8 polymer materials were synthesized and characterized. Intense red emission at 645 nm was observed under UV laser light excitation. Spectroscopic investigations show that the doped materials are suitable for realizing planar optical waveguide amplifiers. About 100 μm wide multimode Sm 3+-doped SU8 channel waveguides were fabricated using a simple UV exposure process. At 250 mW, 351 nm UV pump power, a signal enhancement of ˜7.4 dB at 645 nm was obtained for a 15 mm long channel waveguide.

  10. Observation and analysis of self-amplified spontaneous emission at the APS low-energy undulator test line

    Science.gov (United States)

    Arnold, N. D.; Attig, J.; Banks, G.; Bechtold, R.; Beczek, K.; Benson, C.; Berg, S.; Berg, W.; Biedron, S. G.; Biggs, J. A.; Borland, M.; Boerste, K.; Bosek, M.; Brzowski, W. R.; Budz, J.; Carwardine, J. A.; Castro, P.; Chae, Y.-C.; Christensen, S.; Clark, C.; Conde, M.; Crosbie, E. A.; Decker, G. A.; Dejus, R. J.; DeLeon, H.; Den Hartog, P. K.; Deriy, B. N.; Dohan, D.; Dombrowski, P.; Donkers, D.; Doose, C. L.; Dortwegt, R. J.; Edwards, G. A.; Eidelman, Y.; Erdmann, M. J.; Error, J.; Ferry, R.; Flood, R.; Forrestal, J.; Freund, H.; Friedsam, H.; Gagliano, J.; Gai, W.; Galayda, J. N.; Gerig, R.; Gilmore, R. L.; Gluskin, E.; Goeppner, G. A.; Goetzen, J.; Gold, C.; Gorski, A. J.; Grelick, A. E.; Hahne, M. W.; Hanuska, S.; Harkay, K. C.; Harris, G.; Hillman, A. L.; Hogrefe, R.; Hoyt, J.; Huang, Z.; Jagger, J. M.; Jansma, W. G.; Jaski, M.; Jones, S. J.; Keane, R. T.; Kelly, A. L.; Keyser, C.; Kim, K.-J.; Kim, S. H.; Kirshenbaum, M.; Klick, J. H.; Knoerzer, K.; Koldenhoven, R. J.; Knott, M.; Labuda, S.; Laird, R.; Lang, J.; Lenkszus, F.; Lessner, E. S.; Lewellen, J. W.; Li, Y.; Lill, R. M.; Lumpkin, A. H.; Makarov, O. A.; Markovich, G. M.; McDowell, M.; McDowell, W. P.; McNamara, P. E.; Meier, T.; Meyer, D.; Michalek, W.; Milton, S. V.; Moe, H.; Moog, E. R.; Morrison, L.; Nassiri, A.; Noonan, J. R.; Otto, R.; Pace, J.; Pasky, S. J.; Penicka, J. M.; Pietryla, A. F.; Pile, G.; Pitts, C.; Power, J.; Powers, T.; Putnam, C. C.; Puttkammer, A. J.; Reigle, D.; Reigle, L.; Ronzhin, D.; Rotela, E. R.; Russell, E. F.; Sajaev, V.; Sarkar, S.; Scapino, J. C.; Schroeder, K.; Seglem, R. A.; Sereno, N. S.; Sharma, S. K.; Sidarous, J. F.; Singh, O.; Smith, T. L.; Soliday, R.; Sprau, G. A.; Stein, S. J.; Stejskal, B.; Svirtun, V.; Teng, L. C.; Theres, E.; Thompson, K.; Tieman, B. J.; Torres, J. A.; Trakhtenberg, E. M.; Travish, G.; Trento, G. F.; Vacca, J.; Vasserman, I. B.; Vinokurov, N. A.; Walters, D. R.; Wang, J.; Wang, X. J.; Warren, J.; Wesling, S.; Weyer, D. L.; Wiemerslage, G.; Wilhelmi, K.; Wright, R.; Wyncott, D.; Xu, S.; Yang, B.-X.; Yoder, W.; Zabel, R. B.

    2001-12-01

    Exponential growth of self-amplified spontaneous emission at 530 nm was first experimentally observed at the Advanced Photon Source low-energy undulator test line in December 1999. Since then, further detailed measurements and analysis of the results have been made. Here, we present the measurements and compare these with calculations based on measured electron beam properties and theoretical expectations.

  11. Observation and analysis of self-amplified spontaneous emission at the APS low-energy undulator test line

    CERN Document Server

    Arnold, N D; Banks, G; Bechtold, R; Beczek, K; Benson, C; Berg, S; Berg, W; Biedron, S G; Biggs, J A; Boerste, K; Borland, M; Bosek, M; Brzowski, W R; Budz, J; Carwardine, J A; Castro, P; Chae, Y C; Christensen, S; Clark, C; Conde, M; Crosbie, E A; Decker, G A; Dejus, Roger J; Deleon, H; Den Hartog, P K; Deriy, B N; Dohan, D; Dombrowski, P; Donkers, D; Doose, C L; Dortwegt, R J; Edwards, G A; Eidelman, Y; Erdmann, M J; Error, J J; Ferry, R; Flood, R; Forrestal, J; Freund, H; Friedsam, H; Gagliano, J; Gai, W; Galayda, J N; Gerig, R; Gilmore, R L; Gluskin, E; Goeppner, G A; Goetzen, J; Gold, C; Grelick, A E; Hahne, M W; Hanuska, S; Harkay, K C; Harris, G; Hillman, A L; Hogrefe, R; Hoyt, J; Huang, Z; Jagger, J M; Jansma, W G; Jaski, M; Jones, S J; Keane, R T; Kelly, A L; Keyser, C; Kim, K J; Kim, S H; Kirshenbaum, M; Klick, J H; Knoerzer, K; Knott, M; Koldenhoven, R J; Labuda, S; Laird, R; Lang, J; Lenkszus, F R; Lessner, E S; Lewellen, J W; Li, Y; Lill, R M; Lumpkin, Alex H; Makarov, O A; Markovich, G M; McDowell, M; McDowell, W P; McNamara, P E; Meier, T; Meyer, D; Michalek, W; Milton, S V; Moe, H; Moog, E; Morrison, L; Nassiri, A; Noonan, J R; Otto, R; Pace, J; Pasky, S J; Penicka, J M; Pietryla, A F; Pile, G; Pitts, C; Power, J; Powers, T; Putnam, C C; Puttkammer, A J; Reigle, D; Reigle, L; Ronzhin, D; Rotela, E R; Russell, E F; Sajaev, Vadim; Sarkar, S; Scapino, J C; Schröder, K; Seglem, R A; Sereno, N S; Sharma, S K; Sidarous, J F; Singh, O; Smith, T L; Soliday, R; Sprau, G A; Stein, S J; Stejskal, B; Svirtun, V; Teng, L C; Theres, E; Thompson, K; Tieman, B J; Torres, J A; Trakhtenberg, E; Travish, G; Trento, G F; Vacca, J; Vasserman, I B; Vinokurov, N A; Walters, D R; Wang, J; Wang, X J; Warren, J; Wesling, S; Weyer, D L; Wiemerslage, G; Wilhelmi, K; Wright, R; Wyncott, D; Xu, S; Yang, B X; Yoder, W; Zabel, R B

    2001-01-01

    Exponential growth of self-amplified spontaneous emission at 530 nm was first experimentally observed at the Advanced Photon Source low-energy undulator test line in December 1999. Since then, further detailed measurements and analysis of the results have been made. Here, we present the measurements and compare these with calculations based on measured electron beam properties and theoretical expectations.

  12. Trial manufacture of an insulated amplifier

    International Nuclear Information System (INIS)

    Okuno, Shigeo; Matsuura, Kiyokata.

    1978-10-01

    Trial manufacture of an insulated amplifier was carried out. The input signals are divided by filters Th and Tl into high frequency component and low frequency component. The high frequency component drives a transformer T 1 , and secondary signals are induced. The low frequency component drives a transformer T 2 through a buffer and a modulator. The secondary signals from both transformers are recombined to make the output signals. Compensation for the frequency characteristics of the high frequency transformer and that for the effect of a filter in the demodulation circuit for low frequency component are considered. The time constant of output signals for rectangular input signals was 30 microsec, when only the low frequency part is operated. The drift of the direct current level is within 5 mV. The characteristic features of the high frequency part was also investigated. The overall characteristic features of this amplifier were good for the frequency range of 0 to 500 kHz. (Kato, T.)

  13. Mechanical Amplifier for a Piezoelectric Transducer

    Science.gov (United States)

    Moore, James; Swain, Mark; Lawson, Peter; Calvet, Robert

    2003-01-01

    A mechanical amplifier has been devised to multiply the stroke of a piezoelectric transducer (PZT) intended for use at liquid helium temperatures. Interferometry holds the key to high angular resolution imaging and astrometry in space. Future space missions that will detect planets around other solar systems and perform detailed studies of the evolution of stars and galaxies will use new interferometers that observe at mid- and far-infrared wavelengths. Phase-measurement interferometry is key to many aspects of astronomical interferometry, and PZTs are ideal modulators for most methods of phase measurement, but primarily at visible wavelengths. At far infrared wavelengths of 150 to 300 m, background noise is a severe problem and all optics must be cooled to about 4 K. Under these conditions, piezos are ill-suited as modulators, because their throw is reduced by as much as a factor of 2, and even a wavelength or two of modulation is beyond their capability. The largest commercially available piezo stacks are about 5 in. (12.7 cm) long and have a throw of about 180 m at room temperature and only 90 m at 4 K. It would seem difficult or impossible to use PZTs for phase measurements in the far infrared were it not for the new mechanical amplifier that was designed and built.

  14. Direct solar-pumped iodine laser amplifier

    Science.gov (United States)

    Han, Kwang S.; Hwang, In Heon

    1990-01-01

    The optimum conditions of a solar pumped iodine laser are found in this research for the case of a continuous wave operation and a pulsed operation. The optimum product of the pressure(p) inside the laser tube and the tube diameter(d) was pd=40 approx. 50 torr-cm on the contrary to the case of a high intensity flashlamp pumped iodine laser where the optimum value of the product is known to be pd=150 torr-cm. The pressure-diameter product is less than 1/3 of that of the high power iodine laser. During the research period, various laser materials were also studied for solar pumping. Among the laser materials, Nd:YAG is found to have the lowest laser threshold pumping intensity of about 200 solar constant. The Rhodamine 6G was also tested as the solar pumped laser material. The threshold pumping power was measured to be about 20,000 solar constant. The amplification experiment for a continuously pumped iodine laser amplifier was performed using Vortek solar simulator and the amplification factors were measured for single pass amplification and triple pass amplification of the 15 cm long amplifier tube. The amplification of 5 was obtained for the triple pass amplification.

  15. Discretization analysis of bifurcation based nonlinear amplifiers

    Science.gov (United States)

    Feldkord, Sven; Reit, Marco; Mathis, Wolfgang

    2017-09-01

    Recently, for modeling biological amplification processes, nonlinear amplifiers based on the supercritical Andronov-Hopf bifurcation have been widely analyzed analytically. For technical realizations, digital systems have become the most relevant systems in signal processing applications. The underlying continuous-time systems are transferred to the discrete-time domain using numerical integration methods. Within this contribution, effects on the qualitative behavior of the Andronov-Hopf bifurcation based systems concerning numerical integration methods are analyzed. It is shown exemplarily that explicit Runge-Kutta methods transform the truncated normalform equation of the Andronov-Hopf bifurcation into the normalform equation of the Neimark-Sacker bifurcation. Dependent on the order of the integration method, higher order terms are added during this transformation.A rescaled normalform equation of the Neimark-Sacker bifurcation is introduced that allows a parametric design of a discrete-time system which corresponds to the rescaled Andronov-Hopf system. This system approximates the characteristics of the rescaled Hopf-type amplifier for a large range of parameters. The natural frequency and the peak amplitude are preserved for every set of parameters. The Neimark-Sacker bifurcation based systems avoid large computational effort that would be caused by applying higher order integration methods to the continuous-time normalform equations.

  16. Quantum dots for lasers, amplifiers and computing

    International Nuclear Information System (INIS)

    Bimberg, Dieter

    2005-01-01

    For InAs-GaAs based quantum dot lasers emitting at 1300 nm, digital modulation showing an open eye pattern up to 12 Gb s -1 at room temperature is demonstrated, at 10 Gb s -1 the bit error rate is below 10 -12 at -2 dB m receiver power. Cut-off frequencies up to 20 GHz are realised for lasers emitting at 1.1 μm. Passively mode-locked QD lasers generate optical pulses with repetition frequencies between 5 and 50 GHz, with a minimum Fourier limited pulse length of 3 ps. The uncorrelated jitter is below 1 ps. We use here deeply etched narrow ridge waveguide structures which show excellent performance similar to shallow mesa structures, but a circular far field at a ridge width of 1 μm, improving coupling efficiency into fibres. No beam filamentation of the fundamental mode, low a-factors and strongly reduced sensitivity to optical feedback are observed. QD lasers are thus superior to QW lasers for any system or network. Quantum dot semiconductor optical amplifier (QD SOAs) demonstrate gain recovery times of 120-140 fs, 4-7 times faster than bulk/QW SOAs, and a net gain larger than 0.4 dB/(mm*QD-layer) providing us with novel types of booster amplifiers and Mach-Zehnder interferometers. These breakthroughs became possible due to systematic development of self-organized growth technologies

  17. Development of FIR arrays with integrating amplifiers

    Science.gov (United States)

    Young, Erick T.

    1988-08-01

    The development of optimized photoconductor arrays suitable for far infrared space astronomical applications are described. Although the primary impetus is the production of a 16 by 16 element Ge:Ga demonstration array for SIRTF, the extension of this technology to Large Deployable Reflector (LDR) is considered. The optimization of Ge:Ga and Ge:Be photoconductor materials is discussed. In collaboration with Lawrence Berkeley Laboratory, measurements of FIR photoconductors with quantum efficiencies greater than 20 percent at 100 micrometers, and dark currents below 300 electrons/s are presented. Integrating J-FET amplifier technology is discussed. The current generation of integrating amplifiers has a demonstrated read noise of less than 20 electrons for an integration time of 100 s. The design is shown for a stackable 16 x n Ge:Ga array that utilizes a 16-channel monolithic version of the J-FET integrator. A part of the design is the use of a thin, thermally insulating substrate that allows the electronics to operate at the optimum temperature of 50 K while maintaining thermal and optical isolation from the detectors at 2 K. The power dissipation for the array is less than 16 mW. The array design may particularly be applicable to high resolution imaging spectrometers for LDR.

  18. Multipath interference test method for distributed amplifiers

    Science.gov (United States)

    Okada, Takahiro; Aida, Kazuo

    2005-12-01

    A method for testing distributed amplifiers is presented; the multipath interference (MPI) is detected as a beat spectrum between the multipath signal and the direct signal using a binary frequency shifted keying (FSK) test signal. The lightwave source is composed of a DFB-LD that is directly modulated by a pulse stream passing through an equalizer, and emits the FSK signal of the frequency deviation of about 430MHz at repetition rate of 80-100 kHz. The receiver consists of a photo-diode and an electrical spectrum analyzer (ESA). The base-band power spectrum peak appeared at the frequency of the FSK frequency deviation can be converted to amount of MPI using a calibration chart. The test method has improved the minimum detectable MPI as low as -70 dB, compared to that of -50 dB of the conventional test method. The detailed design and performance of the proposed method are discussed, including the MPI simulator for calibration procedure, computer simulations for evaluating the error caused by the FSK repetition rate and the fiber length under test and experiments on singlemode fibers and distributed Raman amplifier.

  19. Sequence-Related Amplified Polymorphism (SRAP Markers: A Potential Resource for Studies in Plant Molecular Biology

    Directory of Open Access Journals (Sweden)

    Daniel W. H. Robarts

    2014-07-01

    Full Text Available In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR, random-amplified polymorphic DNA (RAPD, and amplified fragment length polymorphism (AFLP to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use. highly variable marker with inherent biological significance.

  20. Direct coupled amplifiers using field effect transistors

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, E P [Control and Instrumentation Division, Atomic Energy Establishment, Winfrith, Dorchester, Dorset (United Kingdom)

    1964-03-15

    The concept of the uni-polar field effect transistor (P.E.T.) was known before the invention of the bi-polar transistor but it is only recently that they have been made commercially. Being produced as yet only in small quantities, their price imposes a restriction on use to circuits where their peculiar properties can be exploited to the full. One such application is described here where the combination of low voltage drift and relatively low input leakage current are necessarily used together. One of the instruments used to control nuclear reactors has a logarithmic response to the mean output current from a polarised ionisation chamber. The logarithmic signal is then differentiated electrically, the result being displayed on a meter calibrated to show the reactor divergence or doubling time. If displayed in doubling time the scale is calibrated reciprocally. Because of the wide range obtained in the logarithmic section and the limited supply voltage, an output of 1 volt per decade change in ionisation current is used. Differentiating this gives a current of 1.5 x 10{sup -8} A for p.s.D. (20 sec. doubling time) in the differentiating amplifier. To overcome some of the problems of noise due to statistical variations in input current, the circuit design necessitates a resistive path to ground at the amplifier input of 20 M.ohms. A schematic diagram is shown. 1. It is evident that a zero drift of 1% can be caused by a leakage current of 1.5 x 10{sup -10} A or an offset voltage of 3 mV at the amplifier input. Although the presently used electrometer valve is satisfactory from the point of view of grid current, there have been sudden changes in grid to grid voltage (the valve is a double triode) of up to 10 m.V. It has been found that a pair of F.E.T's. can be used to replace the electrometer valve so long as care is taken in correct balance of the two devices. An investigation has been made into the characteristics of some fourteen devices to see whether those with

  1. Single-mode operation of a coiled multimode fiber amplifier

    International Nuclear Information System (INIS)

    Koplow, Jeffrey P.; Kliner, Dahv A. V.; Goldberg, Lew

    2000-01-01

    We report a new approach to obtaining single-transverse-mode operation of a multimode fiber amplifier in which the gain fiber is coiled to induce significant bend loss for all but the lowest-order mode. We demonstrated this method by constructing a coiled amplifier using Yb-doped, double-clad fiber with a core diameter of 25 μm and a numerical aperture of ∼0.1 (V≅7.4) . When the amplifier was operated as an amplified-spontaneous-emission source, the output beam had an M 2 value of 1.09±0.09 ; when seeded at 1064 nm, the slope efficiency was similar to that of an uncoiled amplifier. This technique will permit scaling of pulsed fiber lasers and amplifiers to significantly higher pulse energies and peak powers and cw fiber sources to higher average powers while maintaining excellent beam quality. (c) 2000 Optical Society of America

  2. Realization of OFCC based Transimpedance Mode Instrumentation Amplifier

    Directory of Open Access Journals (Sweden)

    Neeta Pandey

    2016-01-01

    Full Text Available The paper presents an instrumentation amplifier suitable for amplifying the current source transducer signals. It provides a voltage output. It has a high gain, common mode rejection ratio and gain independent bandwidth. It uses three Operational Floating Current Conveyors (OFCCs and four resistors. The effect of nonidealities of OFCC on performance of proposed transimpedance instrumentation amplifier (TIA is also analyzed. The proposal has been verified through SPICE simulations using CMOS based schematicThe paper presents an instrumentation amplifier suitable for amplifying the current source transducer signals. It provides a voltage output. It has a high gain, common mode rejection ratio and gain independent bandwidth. It uses three operational floating current conveyors (OFCCs and four resistors. The effect of nonidealities of OFCC on performance of proposed transimpedance instrumentation amplifier (TIA is also analyzed. The proposal has been verified through SPICE simulations using CMOS based schematic.

  3. GaN-based Power amplifiers for microwave applications

    Directory of Open Access Journals (Sweden)

    Jorge Julián Moreno-Rubio

    2016-01-01

    Full Text Available This paper presents a discussion about the design strategies of different kind of power amplifiers for RF/Microwave appli- cations, such as the tuned load power amplifier, class F, class F-1 and Doherty. Furthermore, it is shown the continuous wave characterization of the amplifiers above mentioned. A comparison between the obtained results, in terms of gain, efficiency and output power is presented.

  4. InP Heterojunction Bipolar Transistor Amplifiers to 255 GHz

    Science.gov (United States)

    Radisic, Vesna; Sawdai, Donald; Scott, Dennis; Deal, William; Dang, Linh; Li, Danny; Cavus, Abdullah; To, Richard; Lai, Richard

    2009-01-01

    Two single-stage InP heterojunction bipolar transistor (HBT) amplifiers operate at 184 and 255 GHz, using Northrop Grumman Corporation s InP HBT MMIC (monolithic microwave integrated circuit) technology. At the time of this reporting, these are reported to be the highest HBT amplifiers ever created. The purpose of the amplifier design is to evaluate the technology capability for high-frequency designs and verify the model for future development work.

  5. Functional Blocks and Biquadratic ARC Filters using Transimpedance Amplifiers

    Directory of Open Access Journals (Sweden)

    R. Sarman

    1997-04-01

    Full Text Available The aims of the article are design and analysis of modern circuits including high performance functional blocks and biquadratic filters using transimpedance amplifiers. Here are given various types of these circuits, that works in classical voltage, current or hybrid mode. In this paper are also compared various possibilities of connection of single amplifier filters as for reduction of influence of transimpedance amplifier parasitic elements.

  6. Compressed magnetic flux amplifier with capacitive load

    International Nuclear Information System (INIS)

    Stuetzer, O.M.

    1980-03-01

    A first-order analysis is presented for a compressed magnetic flux (CMF) current amplifier working into a load with a capacitive component. Since the purpose of the investigation was to gain a general understanding of the arrangement, a number of approximations and limitations were accepted. The inductance of the transducer varies with time; the inductance/resistance/capacitance (LRC) circuit therefore is parametric and solutions are different for the stable regime (high C), the oscillation regime (low C), and the transition case. Solutions and performance depend strongly on circuit boundary conditions, i.e., energization of the circuit by either an injected current or by an applied capacitor charge. The behavior of current and energy amplification for the various cases are discussed in detail. A number of experiments with small CMF devices showed that the first-order theory presented predicts transducer performance well in the linear regime

  7. Noise-driven neuromorphic tuned amplifier

    Science.gov (United States)

    Fanelli, Duccio; Ginelli, Francesco; Livi, Roberto; Zagli, Niccoló; Zankoc, Clement

    2017-12-01

    We study a simple stochastic model of neuronal excitatory and inhibitory interactions. The model is defined on a directed lattice and internodes couplings are modulated by a nonlinear function that mimics the process of synaptic activation. We prove that such a system behaves as a fully tunable amplifier: the endogenous component of noise, stemming from finite size effects, seeds a coherent (exponential) amplification across the chain generating giant oscillations with tunable frequencies, a process that the brain could exploit to enhance, and eventually encode, different signals. On a wider perspective, the characterized amplification process could provide a reliable pacemaking mechanism for biological systems. The device extracts energy from the finite size bath and operates as an out of equilibrium thermal machine, under stationary conditions.

  8. Rippled beam free electron laser amplifier

    Science.gov (United States)

    Carlsten, Bruce E.

    1999-01-01

    A free electron laser amplifier provides a scalloping annular electron beam that interacts with the axial electric field of a TM.sub.0n mode. A waveguide defines an axial centerline and, a solenoid arranged about the waveguide produces an axial constant magnetic field within the waveguide. An electron beam source outputs a annular electron beam that interacts with the axial magnetic field to have an equilibrium radius and a ripple radius component having a variable radius with a ripple period along the axial centerline. An rf source outputs an axial electric field that propagates within the waveguide coaxial with the electron beam and has a radial mode that interacts at the electron beam at the equilibrium radius component of the electron beam.

  9. A highly linear power amplifier for WLAN

    International Nuclear Information System (INIS)

    Jin Jie; Shi Jia; Ai Baoli; Zhang Xuguang

    2016-01-01

    A three-stage power amplifier (PA) for WLAN application in 2.4-2.5 GHz is presented. The proposed PA employs an adaptive bias circuit to adjust the operating point of the PA to improve the linearity of the PA. Two methods to short the 2nd harmonic circuit are compared in the area of efficiency and gain of the PA. The PA is taped out in the process of 2 μm InGaP/GaAs HBT and is tested by the evaluation board. The measured results show that 31.5 dB power gain and 29.3 dBm P 1dB with an associated 40.4% power added efficiency (PAE) under the single tone stimulus. Up to 26.5 dBm output power can be achieved with an error vector magnitude (EVM) of lower than 3% under the 64QAM/OFDM WLAN stimulus. (paper)

  10. Optical oscillator-amplifier laser configuration

    International Nuclear Information System (INIS)

    McAllister, G.L.

    1975-01-01

    A laser is described that has incorporated therein an oscillator formed by a pair of mirrors, at least one of the mirrors being positioned outside of the envelope. The mirrors are dimensioned and spaced from each other so that the resonator has a relatively low Fresnel number and is operated unstably. The entire surface of one of these mirrors is convex and diffracts a portion of the energy outside of the oscillator region. Also incorporated into the laser is an amplifier region defined by a separate pair of mirrors which receive the energy diffracted from the oscillator region. The second pair of mirrors form an optical system with a high Fresnel number. A filter, modulator or other control for the laser signal may be placed outside the laser envelope in the optical path of the oscillator

  11. Coherent combination of ultrafast fiber amplifiers

    International Nuclear Information System (INIS)

    Hanna, Marc; Guichard, Florent; Druon, Frédéric; Georges, Patrick; Zaouter, Yoann; Papadopoulos, Dimitris N

    2016-01-01

    We review recent progress in coherent combining of femtosecond pulses amplified in optical fibers as a way to scale the peak and average power of ultrafast sources. Different methods of achieving coherent pulse addition in space (beam combining) and time (divided pulse amplification) domains are described. These architectures can be widely classified into active methods, where the relative phases between pulses are subject to a servomechanism, and passive methods, where phase matching is inherent to the geometry. Other experiments that combine pulses with different spectral contents, pulses that have been nonlinearly broadened or successive pulses from a mode-locked laser oscillator, are then presented. All these techniques allow access to unprecedented parameter range for fiber ultrafast sources. (topical review)

  12. Pulse shaping amplifier (PSA) for nuclear spectroscopy system

    International Nuclear Information System (INIS)

    Lombigit, L.; Maslina Mohd Ibrahim; Nolida Yusup; Nur Aira Abdul Rahman; Yong, C.F.

    2014-01-01

    Pulse Shaping Amplifier (PSA) is an essential components in nuclear spectroscopy system. This networks have two functions; to shape the output pulse and performs noise filtering. In this paper, we describes procedure for design and development of a pulse shaping amplifier which can be used for nuclear spectroscopy system. This prototype was developed using high performance electronics devices and assembled on a FR4 type printed circuit board. Performance of this prototype was tested by comparing it with an equivalent commercial spectroscopy amplifier (Model SILENA 7611). The test results show that the performance of this prototype is comparable to the commercial spectroscopic amplifier. (author)

  13. Ring cavity for a Raman capillary waveguide amplifier

    Science.gov (United States)

    Kurnit, N.A.

    1981-01-27

    A regenerative ring amplifier and regenerative ring oscillator are described which function to feed back a portion of the Stokes signal to complete the ring cavity. The ring cavity configuration allows the CO/sub 2/ laser pump signal and Stokes signal to copropagate through the Raman capillary waveguide amplifier. A Raman capillary waveguide amplifier is also provided in the return leg of the ring cavity to increase gain without increasing the round trip time. Additionally, the ring cavity can be designed such that the amplified Stokes signal is synchronous with the mode-locked spikes of the incoming CO/sub 2/ laser pump signal.

  14. Simultaneous single-shot readout of multi-qubit circuits using a traveling-wave parametric amplifier

    Science.gov (United States)

    O'Brien, Kevin

    Observing and controlling the state of ever larger quantum systems is critical for advancing quantum computation. Utilizing a Josephson traveling wave parametric amplifier (JTWPA), we demonstrate simultaneous multiplexed single shot readout of 10 transmon qubits in a planar architecture. We employ digital image sideband rejection to eliminate noise at the image frequencies. We quantify crosstalk and infidelity due to simultaneous readout and control of multiple qubits. Based on current amplifier technology, this approach can scale to simultaneous readout of at least 20 qubits. This work was supported by the Army Research Office.

  15. Advances in high repetition rate, ultra-short, gigawatt laser systems for time-resolved spectroscopy

    International Nuclear Information System (INIS)

    DiMauro, L.F.

    1991-01-01

    The objective of this article is to emphasize the current advances in the development of high-repetition rate amplifier pumps. Although this review highlights amplifier pump development, any recent data from achieved outputs via the tunable amplifier section is also discussed. The first section describes desirable parameters attributable to the pump amplifier while the rest of the article deals with specific examples for various options. The pump amplifiers can be characterized into two distinct classes; those achieving operation in the hundred hertz regime and those performing at repetition rates ≥1kHz. 23 refs., 4 figs

  16. S-band 300 W pulsed solid state microwave amplifier development for driving high power klystrons for electron accelerators

    International Nuclear Information System (INIS)

    Mohania, Praveen; Shrivastava, Purushottam; Hannurkar, P.R.

    2005-01-01

    S-Band Microwave electron accelerators like microtrons and linear accelerators need pulsed microwaves from few megawatts to tens of megawatts to accelerator the electrons to desired energy and intensity. Klystron tube based driver amplifiers were used to drive the high power klystrons, which need microwave power from few tens of watts to 1 kW depending on tube output power and gain. A endeavour was initiated at Centre for Advanced Technology to develop state of art solid state S-band microwave amplifiers indigenously to drive the klystron tubes. A modular design approach was used and individual modules up to 160 W power levels were developed and tested. Finally combining 160 W modules will give up to 300 W output power. Several more modules can be combined to achieve even high power levels. Present paper describes the developmental efforts of 300 W S-band solid-state amplifiers and related microwave technologies. (author)

  17. FDML swept source at 1060 nm using a tapered amplifier

    DEFF Research Database (Denmark)

    Marschall, Sebastian; Klein, Thomas; Wieser, Wolfgang

    2010-01-01

    We present a novel frequency-swept light source working at 1060nm that utilizes a tapered amplifier as gain medium. These devices feature significantly higher saturation power than conventional semiconductor optical amplifiers and can thus improve the limited output power of swept sources in this...... an axial resolution of 15 µm in air (~11µm in tissue) for OCT applications can be achieved....

  18. Subjective test of class D amplifiers without output filter

    DEFF Research Database (Denmark)

    Agerkvist, Finn T.; Fenger, Lars M.

    2004-01-01

    This paper presents the results of subjective listening tests designed to determine whether the output filter on class D amplifiers used in active loudspeakers can be omitted without audible errors occurring. The frequency range of the amplifiers was limited to 0-3 kHz corresponding to a woofer...

  19. A Power Efficient Audio Amplifier Combining Switching and Linear Techniques

    NARCIS (Netherlands)

    van der Zee, Ronan A.R.; van Tuijl, Adrianus Johannes Maria

    1998-01-01

    Integrated Class D audio amplifiers are very power efficient, but require an external filter which prevents further integration. Also due to this filter, large feedback factors are hard to realise, so that the load influences the distortion- and transfer characteristics. The amplifier presented in

  20. Switching-mode Audio Power Amplifiers with Direct Energy Conversion

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    has been replaced with a high frequency AC link. When compared to the conventional Class D amplifiers with a separate DC power supply, the proposed single conversion stage amplifier provides simple and compact solution with better efficiency and higher level of integration, leading to reduced...

  1. Asymmetric gain-saturated spectrum in fiber optical parametric amplifiers

    DEFF Research Database (Denmark)

    Lali-Dastjerdi, Zohreh; Rottwitt, Karsten; Galili, Michael

    2012-01-01

    We demonstrate experimentally and numerically an unexpected spectral asymmetry in the saturated-gain spectrum of single-pump fiber optical parametric amplifiers. The interaction between higher-order four-wave mixing products and dispersive waves radiated as an effect of third-order dispersion inf...... characteristics of the amplifier and shows local maxima for specific dispersion values....

  2. A high performance electrometer amplifier of hybrid design

    International Nuclear Information System (INIS)

    Rao, N.V.; Nazare, C.K.

    1979-01-01

    A high performance, reliable, electrometer amplifier of hybrid design for low current measurements in mass spectrometers has been developed. The short term instability with a 5 x 10 11 ohms input resistor is less than 1 x 10sup(-15) Amp. The drift is better than 1 mV/hour. The design steps are illustrated with a typical amplifier performance details. (auth.)

  3. Amplified spontaneous emission in solar-pumped iodine laser

    Science.gov (United States)

    Cho, Yong S.; Hwang, In H.; Han, Kwang S.; Lee, Ja H.

    1992-01-01

    The amplified spontaneous emission (ASE) from a long pulse, solar-simulating radiation pumped iodine laser amplifier is studied. The ASE threshold pump intensity is almost proportional to the inverse of the laser gain length when the gas pressure is constant in the laser tube.

  4. A Review of High Voltage Drive Amplifiers for Capacitive Actuators

    DEFF Research Database (Denmark)

    Huang, Lina; Zhang, Zhe; Andersen, Michael A. E.

    2012-01-01

    This paper gives an overview of the high voltage amplifiers, which are used to drive capacitive actuators. The amplifiers for both piezoelectric and DEAP (dielectric electroactive polymer) actuator are discussed. The suitable topologies for driving capacitive actuators are illustrated in detail...

  5. Efficiency of random amplified polymorphic DNA (RAPD) and inter ...

    African Journals Online (AJOL)

    Efficiency of random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) markers for genotype fingerprinting and genetic diversity studies in canola ( ) ... The number of amplified fragments with RAPD primers ranged from 8 to 21, with the size of amplicons ranging from 162 to 3154 bp.

  6. Gain characteristics of a saturated fiber optic parametric amplifier

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Lorenzen, Michael Rodas; Noordegraaf, Danny

    2008-01-01

    In this work we discuss saturation performance of a fiber optic parametric amplifier. A simple numerical model is described and applied to specific cases. A system experiment using a saturated amplifier illustrates a 4 dB improvement in required signal to noise ratio for a fixed bit error ratio....

  7. 47 CFR 2.815 - External radio frequency power amplifiers.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false External radio frequency power amplifiers. 2... AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.815 External radio frequency power amplifiers. (a) As used in this part, an external radio frequency power...

  8. Ultrafast Dynamics of Quantum-Dot Semiconductor Optical Amplifiers

    DEFF Research Database (Denmark)

    Poel, Mike van der; Hvam, Jørn Märcher

    2007-01-01

    We report on a series of experiments on the dynamical properties of quantum-dot semiconductor optical amplifiers. We show how the amplifier responds to one or several ultrafast (170 fs) pulses in rapid succession and our results demonstrate applicability and ultimate limitations to application...

  9. Series-Tuned High Efficiency RF-Power Amplifiers

    DEFF Research Database (Denmark)

    Vidkjær, Jens

    2008-01-01

    An approach to high efficiency RF-power amplifier design is presented. It addresses simultaneously efficiency optimization and peak voltage limitations when transistors are pushed towards their power limits.......An approach to high efficiency RF-power amplifier design is presented. It addresses simultaneously efficiency optimization and peak voltage limitations when transistors are pushed towards their power limits....

  10. External Peltier Cooler For Low-Noise Amplifier

    Science.gov (United States)

    Soper, Terry A.

    1990-01-01

    Inexpensive Peltier-effect cooling module made of few commercially available parts used to reduce thermal noise in microwave amplifier. Retrofitted to almost any microwave low-noise amplifier or receiver preamplifier used in communication, telemetry, or radar. Includes copper or aluminum cold plate held tightly against unit to be cooled by strap-type worm-gear clamps.

  11. Slow Light at High Frequencies in an Amplifying Semiconductor Waveguide

    DEFF Research Database (Denmark)

    Öhman, Filip; Yvind, Kresten; Mørk, Jesper

    2006-01-01

    We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz.......We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz....

  12. Modeling Distortion Effects in Class-D Amplifier Filter Inductors

    DEFF Research Database (Denmark)

    Knott, Arnold; Stegenborg-Andersen, Tore; Thomsen, Ole Cornelius

    2010-01-01

    Distortion is generally accepted as a quantifier to judge the quality of audio power amplifiers. In switchmode power amplifiers various mechanisms influence this performance measure. After giving an overview of those, this paper focuses on the particular effect of the nonlinearity of the output f...

  13. CARM and harmonic gyro-amplifier experiments at 17 GHz

    International Nuclear Information System (INIS)

    Menninger, W.L.; Danly, B.G.; Alberti, S.; Chen, C.; Rullier, J.L.; Temkin, R.J.

    1993-01-01

    Cyclotron resonance maser amplifiers are possible sources for applications such as electron cyclotron resonance heating of fusion plasmas and driving high-gradient rf linear accelerators. For accelerator drivers, amplifiers or phase locked-oscillators are required. A 17 GHz cyclotron autoresonance maser (CARM) amplifier experiment and a 17 GHz third harmonic gyro-amplifier experiment are presently underway at the MIT Plasma Fusion Center. Using the SRL/MIT SNOMAD II introduction accelerator to provide a 380 kV, 180 A, 30 ns flat top electron beam, the gyro-amplifier experiment has produced 5 MW of rf power with over 50 dB of gain at 17 GHz. The gyro-amplifier operates in the TE 31 mode using a third harmonic interaction. Because of its high power output, the gyro-amplifier will be used as the rf source for a photocathode rf electron gun experiment also taking place at MIT. Preliminary gyro-amplifier results are presented, including measurement of rf power, gain versus interaction length, and the far-field pattern. A CARM experiment designed to operate in the TE 11 mode is also discussed

  14. A Transimpedance Amplifier for Remotely Located Quartz Tuning Forks

    OpenAIRE

    Kleinbaum, Ethan; Csathy, Gabor

    2012-01-01

    The cable capacitance in cryogenic and high vacuum applications of quartz tuning forks imposes severe constraints on the bandwidth and noise performance of the measurement. We present a single stage low noise transimpedance amplifier with a bandwidth exceeding 1 MHz and provide an in-depth analysis of the dependence of the amplifier parameters on the cable capacitance.

  15. Note: a transimpedance amplifier for remotely located quartz tuning forks.

    Science.gov (United States)

    Kleinbaum, Ethan; Csáthy, Gábor A

    2012-12-01

    The cable capacitance in cryogenic and high vacuum applications of quartz tuning forks imposes severe constraints on the bandwidth and noise performance of the measurement. We present a single stage low noise transimpedance amplifier with a bandwidth exceeding 1 MHz and provide an in-depth analysis of the dependence of the amplifier parameters on the cable capacitance.

  16. Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

    Science.gov (United States)

    Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

  17. PHEMT Distributed Power Amplifier Adopting Broadband Impedance Transformer

    DEFF Research Database (Denmark)

    Narendra, K.; Limiti, E.; Paoloni, C.

    2013-01-01

    A non-uniform drain line distributed power amplifier (DPA) employing a broadband impedance transformer is presented. The DPA is based on GaAs PHEMT technology. The impedance transformer employs asymmetric coupled lines and transforms a low output impedance of the amplifier to a standard 50 Ω...

  18. Traveling-Wave Tube Amplifier for THz Frequencies

    DEFF Research Database (Denmark)

    Kotiranta, Mikko; Krozer, Viktor; Zhurbenko, Vitaliy

    tubes and gas lasers, but the ones available are too expensive or large for many applications. This work is related to the European project OPTHER (Optically driven terahertz amplifiers) which aims to realise a compact, powerful and efficient vacuum tube amplifier for the frequency range of 0.3 – 2...

  19. Amplifying Islam : Pluralism, Secularism, and Religious Sounds in The Netherlands

    NARCIS (Netherlands)

    Tamimi Arab, P.

    2015-01-01

    This dissertation is an ethnographic study of the amplified azan, the Islamic call to prayer, in the Netherlands, adding a sonic dimension to analyses of the politics of Islamic aesthetics in the western world. Often rejected by opponents as noise pollution, facilitating the amplified azan is an

  20. Advances in microwaves

    CERN Document Server

    Young, Leo

    1967-01-01

    Advances in Microwaves, Volume 2 focuses on the developments in microwave solid-state devices and circuits. This volume contains six chapters that also describe the design and applications of diplexers and multiplexers. The first chapter deals with the parameters of the tunnel diode, oscillators, amplifiers and frequency converter, followed by a simple physical description and the basic operating principles of the solid state devices currently capable of generating coherent microwave power, including transistors, harmonic generators, and tunnel, avalanche transit time, and diodes. The next ch

  1. Quantum Dot Semiconductor Optical Amplifiers - Physics and Applications

    DEFF Research Database (Denmark)

    Berg, Tommy Winther

    2004-01-01

    This thesis describes the physics and applications of quantum dot semiconductor optical amplifiers based on numerical simulations. These devices possess a number of unique properties compared with other types of semiconductor amplifiers, which should allow enhanced performance of semiconductor...... respects is comparable to those of fiber amplifiers. The possibility of inverting the optically active states to a large degree is essential in order to achieve this performance. Optical signal processing through cross gain modulation and four wave mixing is modeled and described. For both approaches...... and QW devices and to experiments on quantum dot amplifiers. These comparisons outline the qualitative differences between the different types of amplifiers. In all cases focus is put on the physical processes responsible the differences....

  2. Low-cost amplifier for alpha detection with photodiode

    Energy Technology Data Exchange (ETDEWEB)

    Domienikan, Cláudio; Costa, Priscila; Genezini, Frederico A.; Zahn, Guilherme S., E-mail: clanikan@ipen.br, E-mail: pcosta@ipen.br, E-mail: fredzini@ipen.br, E-mail: gzahn@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    A low-cost amplifier for Hamamatsu S3590-09 PIN photodiode to be used in alpha detection is presented. This amplifier consists basically of two circuits: a pulse preamplifier and a shaper-driver. The PIN photodiode is reverse-biased and connected to a charge preamplifier input. Incident alpha particles generate a small current pulse in the photodiode. The integrating circuit of the low noise preamplifier transforms current pulse into a voltage pulse with amplitude proportional to the charge carried by the current pulse. The shaper-driver consists of a differentiator and an integrator and is responsible for filtering and further amplifying the preamplifier signal, generating a NIM-compatible energy pulse. The performance of the set photodiode-amplifier was successively tested through the use of a {sup 243}Am radioactive source. The low-cost photodiode amplifier was designed and constructed at IPEN - CNEN/SP using national components and expertise. (author)

  3. Efficient and Compact Optical Amplifier Using EYDF

    Directory of Open Access Journals (Sweden)

    Sulaiman Wadi Harun

    2010-09-01

    Full Text Available An efficient Erbium/Ytterbium doped fiber amplifier (EYDFA is demonstrated using a 1058nm pumping wavelength, where the amplification is assisted by energy transfer between Yb and Er ions. The energy transfer increases the limit of erbium doping concentration that is imposed by concentration quenching in Erbium-doped fiber (EDF. Therefore, the gain and noise figure are severely degraded with 1480 nm pumping, where the energy transfer cannot be achieved. The use of optical isolator improves the small signal gain and noise figure by about 4.8 dB and 1.6 dB, respectively. By employing a double-pass configuration, a higher gain can be obtained with an expense of a noise figure penalty. The gain improvement of 17.0 dB is obtained at 20 mW and -50 dBm of pump and input signal powers. This shows that the double-pass configuration is an important aspect to consider when designing an efficient EYDFA.

  4. Direct solar-pumped iodine laser amplifier

    Science.gov (United States)

    Han, Kwang S.

    1987-01-01

    This semiannual progress report covers the period from March 1, 1987 to September 30, 1987 under NASA grant NAG1-441 entitled 'Direct solar-pumped iodine laser amplifier'. During this period Nd:YAG and Nd:Cr:GSGG crystals have been tested for the solar-simulator pumped cw laser, and loss mechanisms of the laser output power in a flashlamp-pumped iodine laser also have been identified theoretically. It was observed that the threshold pump-beam intensities for both Nd:YAG and Nd:Cr:GSGG crystals were about 1000 solar constants, and the cw laser operation of the Nd:Cr:GSGG crystal was more difficult than that of the Nd:YAG crystal under the solar-simulator pumping. The possibility of the Nd:Cr:GSGG laser operation with a fast continuously chopped pumping was also observed. In addition, good agreement between the theoretical calculations and the experimental data on the loss mechanisms of a flashlamp-pumped iodine laser at various fill pressures and various lasants was achieved.

  5. Gold Nanoparticle Labels Amplify Ellipsometric Signals

    Science.gov (United States)

    Venkatasubbarao, Srivatsa

    2008-01-01

    The ellipsometric method reported in the immediately preceding article was developed in conjunction with a method of using gold nanoparticles as labels on biomolecules that one seeks to detect. The purpose of the labeling is to exploit the optical properties of the gold nanoparticles in order to amplify the measurable ellipsometric effects and thereby to enable ultrasensitive detection of the labeled biomolecules without need to develop more-complex ellipsometric instrumentation. The colorimetric, polarization, light-scattering, and other optical properties of nanoparticles depend on their sizes and shapes. In the present method, these size-and-shape-dependent properties are used to magnify the polarization of scattered light and the diattenuation and retardance of signals derived from ellipsometry. The size-and-shape-dependent optical properties of the nanoparticles make it possible to interrogate the nanoparticles by use of light of various wavelengths, as appropriate, to optimally detect particles of a specific type at high sensitivity. Hence, by incorporating gold nanoparticles bound to biomolecules as primary or secondary labels, the performance of ellipsometry as a means of detecting the biomolecules can be improved. The use of gold nanoparticles as labels in ellipsometry has been found to afford sensitivity that equals or exceeds the sensitivity achieved by use of fluorescence-based methods. Potential applications for ellipsometric detection of gold nanoparticle-labeled biomolecules include monitoring molecules of interest in biological samples, in-vitro diagnostics, process monitoring, general environmental monitoring, and detection of biohazards.

  6. Status Report on the Energy Amplifier

    CERN Document Server

    Rubbia, Carlo

    1994-01-01

    0ne year after its first presentation,the Energy Amplifier (EA) Project holds its promises for a environmentally acceptable form of energy extraction from nuclei, namely to eliminate or at least greatly reduce(i) the environmental impact of the long-lived highly radioactive waste;(ii) the possibility of diversions toward military applications;(iii) the risks of an accidental divergence related to the critical operation of the chain reaction and (iv) make a more efficient use of a fuel which is less radio-toxic to extract and more abundant on Earth than Uranium. In these respects the EA (or equivalent scenarios from Los Alamos and elsewhere) is comparable in performance to Thermonuclear Fusion. Bot h approches offer pratically unl;imited fuel resources: the energetic content of Lithium on the Earth's crust needed by Fusion is estimated to be seven times the one of Thorium and they are both adequate for millions of years of very intensived utilisation.However the EA can be built economically,in a variety of siz...

  7. Stochastic phenomena in a fiber Raman amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Kalashnikov, Vladimir [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Institute of Photonics, Vienna University of Technology (Austria); Sergeyev, Sergey V. [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Ania-Castanon, Juan Diego [Instituto de Optica CSIC, Madrid (Spain); Jacobsen, Gunnar [Acreo, Kista (Sweden); Popov, Sergei [Royal Institute of Technology (KTH), Stockholm (Sweden)

    2017-01-15

    The interplay of such cornerstones of modern nonlinear fiber optics as a nonlinearity, stochasticity and polarization leads to variety of the noise induced instabilities including polarization attraction and escape phenomena harnessing of which is a key to unlocking the fiber optic systems specifications required in high resolution spectroscopy, metrology, biomedicine and telecommunications. Here, by using direct stochastic modeling, the mapping of interplay of the Raman scattering-based nonlinearity, the random birefringence of a fiber, and the pump-to-signal intensity noise transfer has been done in terms of the fiber Raman amplifier parameters, namely polarization mode dispersion, the relative intensity noise of the pump laser, fiber length, and the signal power. The obtained results reveal conditions for emergence of the random birefringence-induced resonance-like enhancement of the gain fluctuations (stochastic anti-resonance) accompanied by pulse broadening and rare events in the form of low power output signals having probability heavily deviated from the Gaussian distribution. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. A highly linear power amplifier for WLAN

    Science.gov (United States)

    Jie, Jin; Jia, Shi; Baoli, Ai; Xuguang, Zhang

    2016-02-01

    A three-stage power amplifier (PA) for WLAN application in 2.4-2.5 GHz is presented. The proposed PA employs an adaptive bias circuit to adjust the operating point of the PA to improve the linearity of the PA. Two methods to short the 2nd harmonic circuit are compared in the area of efficiency and gain of the PA. The PA is taped out in the process of 2 μm InGaP/GaAs HBT and is tested by the evaluation board. The measured results show that 31.5 dB power gain and 29.3 dBm P1dB with an associated 40.4% power added efficiency (PAE) under the single tone stimulus. Up to 26.5 dBm output power can be achieved with an error vector magnitude (EVM) of lower than 3% under the 64QAM/OFDM WLAN stimulus. Project supported by the National Natural Science Foundation of China (No. 61201244) and the Natural Science Fund of SUES (No. E1-0501-14-0168).

  9. Spectral hole-burning and carrier-heating dynamics in quantum-dot amplifiers: Comparison with bulk amplifiers

    DEFF Research Database (Denmark)

    Borri, P.; Langbein, W.; Hvam, Jørn Märcher

    2001-01-01

    The ultrafast gain dynamics in an electrically pumped InAs/InGaAs/GaAs quantum-dot amplifier are measured at room temperature with femtosecond resolution, and compared with results on an InGaAsP bulk amplifier. The role of spectral hole burning and carrier heating in the recovery of the gain...

  10. AN APPLICATION OF ELECTRONIC AMPLIFIER STETHOSCOPE

    Directory of Open Access Journals (Sweden)

    Alper KAÇAR

    2014-05-01

    Full Text Available Electronic stethoscopes are one of the important medical devices which affects the self-diagnostic or remote diagnostic in medical area. Rather the general stethoscopes, electronic ones increases the sound amplitude and quality. By filtering ambient noise, they can be used for advance analysis of heart or lung related diseases.

  11. Nitric oxide amplifies the rat electroretinogram.

    Science.gov (United States)

    Vielma, Alex; Delgado, Luz; Elgueta, Claudio; Osorio, Rodrigo; Palacios, Adrián G; Schmachtenberg, Oliver

    2010-11-01

    It is well established that nitric oxide (NO) participates in retinal signal processing through stimulation of its receptor enzyme, soluble guanylyl cyclase (sGC). However, under pathological conditions such as uveoretinitis, diabetic or ischemic retinopathy, elevated NO concentrations may cause protein S-nitrosation and peroxynitrite formation in the retina, promoting cellular injury and apoptosis. Previous electroretinogram (ERG) studies demonstrated deleterious effects of NO on the retinal light response, but showed no evidence for a role in normal signal processing. To better understand the function of NO in ocular physiology, we investigated the effects of exogenous NO, produced by NO donors with different release kinetics, on the flash ERG of the rat. Within a limited concentration range, NO strongly amplified ERG a- and b-waves, oscillatory potentials, and the scotopic threshold response. Amplification exceeded 100% under dark adaptation, whereas the photopic ERG and the isolated cone response were increased by less than 50%. Blocking photoreceptor-bipolar cell synapses by AP-4 demonstrated a significant increase of the isolated a-wave by NO, and modeling the ERG generator PIII supported photoreceptors as primary NO targets. The sGC inhibitors ODQ and NS2028 did not reduce NO-dependent ERG amplification, ruling out an involvement of the classical NO effector cyclic GMP. Using immunohistochemistry, we show that illumination and exogenous NO altered the S-nitrosation level of the photoreceptor layer, suggesting that direct protein modifications caused by elevated levels of NO may be responsible for the observed phenomenon. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Methylphenidate alters selective attention by amplifying salience.

    Science.gov (United States)

    ter Huurne, Niels; Fallon, Sean James; van Schouwenburg, Martine; van der Schaaf, Marieke; Buitelaar, Jan; Jensen, Ole; Cools, Roshan

    2015-12-01

    Methylphenidate, the most common treatment of attention deficit hyperactivity disorder (ADHD), is increasingly used by healthy individuals as a "smart drug" to enhance cognitive abilities like attention. A key feature of (selective) attention is the ability to ignore irrelevant but salient information in the environment (distractors). Although crucial for cognitive performance, until now, it is not known how the use of methylphenidate affects resistance to attentional capture by distractors. The present study aims to clarify how methylphenidate affects distractor suppression in healthy individuals. The effect of methylphenidate (20 mg) on distractor suppression was assessed in healthy subjects (N = 20), in a within-subject double-blind placebo-controlled crossover design. We used a visuospatial attention task with target faces flanked by strong (faces) or weak distractors (scrambled faces). Methylphenidate increased accuracy on trials that required gender identification of target face stimuli (methylphenidate 88.9 ± 1.4 [mean ± SEM], placebo 86.0 ± 1.2 %; p = .003), suggesting increased processing of the faces. At the same time, however, methylphenidate increased reaction time when the target face was flanked by a face distractor relative to a scrambled face distractor (methylphenidate 34.9 ± 3.73, placebo 26.7 ± 2.84 ms; p = .027), suggesting enhanced attentional capture by distractors with task-relevant features. We conclude that methylphenidate amplifies salience of task-relevant information at the level of the stimulus category. This leads to enhanced processing of the target (faces) but also increased attentional capture by distractors drawn from the same category as the target.

  13. Direct solar-pumped iodine laser amplifier

    Science.gov (United States)

    Han, Kwang S.; Hwang, In Heon; Kim, Khong Hon; Stock, Larry V.

    1988-01-01

    A XeCl laser pumped iodine laser oscillator was developed which will be incorporated into the Master Oscillator Power Amplifier (MOPA) system. The developed XeCl laser produces output energy of about 60 mJ per pulse. The pulse duration was about 10 nsec. The kinetic model for the solar-pumped laser was refined and the algorithm for the calculation of a set of rate equations was improved to increase the accuracy and the efficiency of the calculation. The improved algorithm was applied to explain the existing experimental data taken from a flashlamp pumped iodine laser for three kinds of lasants, i-C3F7I, n-C4F9I, and t-C4F9I. Various solid laser materials were evaluated for solar-pumping. The materials studied were Nd:YAG, Nd:YLF, and Cr:Nd:GSGG crystals. The slope efficiency of 0.17 percent was measured for the Nd:YLF near the threshold pump intensity which was 211 solar constants (29W/sq cm). The threshold pump intensity of the Nd:YAG was measured to be 236 solar constants (32W/sq cm) and the near-threshold slope efficiency was 0.12 percent. True CW laser operation of Cr:Nd:GSGG was possible only at pump intensities less than or equal to 1,500 solar constants (203 W/sq cm). This fact was attributed to the high thermal focusing effect of the Cr:Nd:GSGG rod.

  14. A modular positive feedback-based gene amplifier

    Directory of Open Access Journals (Sweden)

    Bhalerao Kaustubh D

    2010-02-01

    Full Text Available Abstract Background Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors. Results We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity. Conclusions The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

  15. Detection of weak optical signals with a laser amplifier

    International Nuclear Information System (INIS)

    Kozlovskii, A. V.

    2006-01-01

    Detection of weak and extremely weak light signals amplified by linear and four-wave mixing laser amplifiers is analyzed. Photoelectron distributions are found for different input photon statistics over a wide range of gain. Signal-to-noise ratios are calculated and analyzed for preamplification schemes using linear and four-wave mixing amplifiers. Calculations show that the high signal-to-noise ratio (much higher than unity), ensuring reliable detection of weak input signals, can be attained only with a four-wave mixing preamplification scheme. Qualitative dependence of the signal-to-noise ratio on the quantum statistical properties of both signal and idler waves is demonstrated

  16. Class-D audio amplifiers with negative feedback

    OpenAIRE

    Cox, Stephen M.; Candy, B. H.

    2006-01-01

    There are many different designs for audio amplifiers. Class-D, or switching, amplifiers generate their output signal in the form of a high-frequency square wave of variable duty cycle (ratio of on time to off time). The square-wave nature of the output allows a particularly efficient output stage, with minimal losses. The output is ultimately filtered to remove components of the spectrum above the audio range. Mathematical models are derived here for a variety of related class-D amplifier de...

  17. Efficient performance simulation of class D amplifier output stages

    DEFF Research Database (Denmark)

    Nyboe, Flemming; Risbo, Lars; Andreani, Pietro

    2005-01-01

    Straightforward simulation of amplifier distortion involves transient simulation of operation on a sine wave input signal, and a subsequent FFT of the output voltage. This approach is very slow on class D amplifiers, since the switching behavior forces simulation time steps that are many orders...... of magnitude smaller than the duration of one period of an audio sine wave. This work presents a method of simulating the amplifier transfer characteristic using a minimum amount of simulation time, and then deriving THD from the results....

  18. Integrated wide-band low-background amplifiers

    International Nuclear Information System (INIS)

    Il'yushchenko, I.I.

    1980-01-01

    Ways of increasing stability and reproduction of characteristics of wide-band integral amplifiers that would to the least extent increase their background noises, are discussed. Considered are some certain flowsheets of integral wide-band amplifiers with low background noise of foreign production which differ from one another by construction of inlet cascades as well as by the applied feedback type. The principal flowsheets of the amplifiers and their main performances are presented. The analysis of the data obtained has revealed that microcircuits made of cascades with a common emitter and local combined feedback are most wide-band among all the considered microcircuits [ru

  19. Model of pulse extraction from a copper laser amplifier

    International Nuclear Information System (INIS)

    Boley, C.D.; Warner, B.E.

    1997-03-01

    A computational model of pulse propagation through a copper laser amplifier has been developed. The model contains a system of 1-D (in the axial direction), time-dependent equations for the laser intensity and amplified spontaneous emission (ASE), coupled to rate equations for the atomic levels. Detailed calculations are presented for a high-power amplifier at Lawrence Livermore National Laboratory. The extracted power agrees with experiment near saturation. At lower input power the calculation overestimates experiment, probably because of increased ASE effects. 6 refs., 6 figs

  20. Using MEMS Capacitive Switches in Tunable RF Amplifiers

    OpenAIRE

    Danson John; Plett Calvin; Tait Niall

    2006-01-01

    A MEMS capacitive switch suitable for use in tunable RF amplifiers is described. A MEMS switch is designed, fabricated, and characterized with physical and RF measurements for inclusion in simulations. Using the MEMS switch models, a dual-band low-noise amplifier (LNA) operating at GHz and GHz, and a tunable power amplifier (PA) at GHz are simulated in m CMOS. MEMS switches allow the LNA to operate with 11 dB of isolation between the two bands while maintaining dB of gain and sub- dB no...

  1. Influence of mode competition on beam quality of fiber amplifier

    International Nuclear Information System (INIS)

    Xiao Qi-Rong; Yan Ping; Sun Jun-Yi; Chen Xiao; Ren Hai-Cui; Gong Ma-Li

    2014-01-01

    Theoretical and experimental studies of the influence of the mode competition on the output beam quality of fiber amplifiers are presented. Rate equations and modal decomposition method are used in the theoretical model. In the experiment, the output beam-quality factor of a fiber amplifier, which is based on a Yb-doped double-clad large mode area fiber as a function of the seed beam quality and the pump power of the amplifier, is measured. The experimental results are consistent with the theoretical analysis. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  2. Minimizing Crosstalk in Self Oscillating Switch Mode Audio Power Amplifiers

    DEFF Research Database (Denmark)

    Knott, Arnold; Ploug, Rasmus Overgaard

    2012-01-01

    a method to minimize this phenomenon by improving the integrity of the various power distribution systems of the amplifier. The method is then applied to an amplifier built for this investigation. The results show that the crosstalk is suppressed with 30 dB, but is not entirely eliminated......The varying switching frequencies of self oscillating switch mode audio amplifiers have been known to cause interchannel intermodulation disturbances in multi channel configurations. This crosstalk phenomenon has a negative impact on the audio performance. The goal of this paper is to present...

  3. Radiofrequency amplifier based on a DC superconducting quantum interference device

    International Nuclear Information System (INIS)

    Martinis, J.M.; Hilbert, C.; Clarke, J.

    1986-01-01

    A method is described of amplifying a radiofrequency signal consisting of: disposing a single symmetrically biased dc SQUID and an input coil within a superconducting shield, the dc SQUID having a superconducting ring interrupted by two shunted Josephson junctions, and the input coil being inductively coupled solely to the ring of the single SQUID, establishing a constant magnetic flux threading the SQUID ring, applying the radiofrequency signal to the input coil from outside of the superconducting shield, obtaining an amplified radiofrequency signal solely from across the ring of the single SQUID, transmitting the amplified radiofrequency signal from across the SQUID ring to the outside of the superconducting shield

  4. Design and Fabrication of a 1 THz Backward Wave Amplifier

    DEFF Research Database (Denmark)

    Paoloni, Claudio; Di Carlo, Aldo; Brunetti, Francesca

    2011-01-01

    , to get a level of output power to enable applications at these frequencies. The OPTHER (Optically driven THz amplifier) project, funded by the European Community, is on the road to realize the first 1 THz vacuum tube amplifier. Technology at the state of the art has been used for the realization...... of the parts with dimensions supporting THz frequencies. A backward wave amplifier configuration is chosen to make the parts realizable. A carbon nanotube cold cathode has been considered for electron generation. A thermionic micro electron gun is designed to test the tube. A novel slow-wave structure (SWS...

  5. Introduction to RF power amplifier design and simulation

    CERN Document Server

    Eroglu, Abdullah

    2015-01-01

    Introduction to RF Power Amplifier Design and Simulation fills a gap in the existing literature by providing step-by-step guidance for the design of radio frequency (RF) power amplifiers, from analytical formulation to simulation, implementation, and measurement. Featuring numerous illustrations and examples of real-world engineering applications, this book:Gives an overview of intermodulation and elaborates on the difference between linear and nonlinear amplifiersDescribes the high-frequency model and transient characteristics of metal-oxide-semiconductor field-effect transistorsDetails activ

  6. Gyrocon: a deflection-modulated, high-power microwave amplifier

    International Nuclear Information System (INIS)

    Tallerico, P.J.

    1977-10-01

    A large-signal, relativistic theory of the electron-field interaction in a new class of microwave amplifiers is presented and applied to the analysis of a high-power, 450-MHz amplifier for accelerator applications. The analysis indicates that electronic efficiencies in excess of 90 percent are obtainable and that overall efficiencies of 90 percent are possible. The amplifier is unique in several respects; the electron velocity is perpendicular to the circuit energy flow, the device uses a fast-wave circuit, and the electron beam is deflection modulated

  7. Designing and development of a synchronous analogic amplifier

    International Nuclear Information System (INIS)

    De la Hoz, E.; Ortiz, A.

    1989-01-01

    A large number of electronic systems used in the measurement and analysis of weak signals involve a ''lock-in'' amplifier, because it provides an effective method for the recovery of signals buried below a considerable high level of noise. The use of the ''lock-in'' amplifier in our institutions is very limited due to the high expense and the lack of warranties for its maintenance. The purpose of the present work is to design and build a low cost ''lock-in'' amplifier using components available in the local market. Its optimization has allowed us to increase the sensitivity and linearity of the systems, making it very versatile for dedicated applications

  8. Amplify scientific discovery with artificial intelligence

    Energy Technology Data Exchange (ETDEWEB)

    Gil, Yolanda; Greaves, Mark T.; Hendler, James; Hirsch, Hyam

    2014-10-10

    Computing innovations have fundamentally changed many aspects of scientific inquiry. For example, advances in robotics, high-end computing, networking, and databases now underlie much of what we do in science such as gene sequencing, general number crunching, sharing information between scientists, and analyzing large amounts of data. As computing has evolved at a rapid pace, so too has its impact in science, with the most recent computing innovations repeatedly being brought to bear to facilitate new forms of inquiry. Recently, advances in Artificial Intelligence (AI) have deeply penetrated many consumer sectors, including for example Apple’s Siri™ speech recognition system, real-time automated language translation services, and a new generation of self-driving cars and self-navigating drones. However, AI has yet to achieve comparable levels of penetration in scientific inquiry, despite its tremendous potential in aiding computers to help scientists tackle tasks that require scientific reasoning. We contend that advances in AI will transform the practice of science as we are increasingly able to effectively and jointly harness human and machine intelligence in the pursuit of major scientific challenges.

  9. Modeling FWM and impairments aware amplifiers placement technique for an optical MAN/WAN: Inline amplifiers case

    Science.gov (United States)

    Singh, Gurpreet; Singh, Maninder Lal

    2015-08-01

    A new four wave mixing (FWM) model for an optical network with amplifiers and a comparative analysis among three proposed amplifiers placement techniques have been presented in this paper. The FWM model is validated with the experimental measured data. The novelty of this model is its uniqueness that on direct substitutions of network parameters like length, it works even for unequal inter amplifier separations. The novelty of the analysis done among three schemes is that it presents fair choice of amplifiers placement methods for varied total system length. The appropriateness of these three schemes has been analyzed on the basis of critical system length, critical number of amplifiers and critical bit error rate (10-9) in presence of four wave mixing (FWM) and amplified spontaneous emission noise (ASE). The implementation of analysis done has been given with the help of an example of a regenerative metropolitan area network (MAN). The results suggest that the decreasing fiber section scheme should be avoided for placements of amplifiers and schemes IUFS and EFS shows their importance interchangeably for different set of parameters.

  10. Compact solid state radio frequency amplifiers in kW regime for ...

    Indian Academy of Sciences (India)

    RF amplifier; solid state amplifier; power combiner and divider; .... was designed using planar and coaxial transmission line baluns with minimum lumped variable ..... Cripps S C 1999 RF power amplifiers for wireless communication. Norwood: ...

  11. Role of Integrin Alpha 5 in ErbB2-Mediated Breast Cancer

    Science.gov (United States)

    2009-09-01

    AD__ ( Leave blank) _______________ Award Number: W81XWH-08-1...3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 using Guava Technologies EasyCyte Plus, and data analyzed with Guava ...dilution, washed, and incubated with secondary antibody (AlexaFluor mouse 488, Invitrogen) at a 1:200 dilution. Cells were read on a Guava Technologies

  12. LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

    DEFF Research Database (Denmark)

    Chang, Joan; Nicolau, Monica; Cox, Thomas R

    2013-01-01

    Lysyl oxidase-like 2 (LOXL2) is a matrix remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigate the effects of LOXL2 expression in normal mammary...... epithelial cells in order to gain insight into how LOXL2 mediates cancer progression....

  13. The Effects of Bisphenol A (BPA) on ErbB2 Positive Breast Cancer

    Science.gov (United States)

    2010-11-01

    adolescence [2]. As this population of women prenatally exposed to DES has aged, it has become increasingly apparent that they are also more susceptible...of action is implicated. Fertil Steril, 2008. 89(2 Suppl): p. e41. 27. Timms, B.G., et al., Estrogenic chemicals in plastic and oral contraceptives

  14. Erbb2 Is Required for Cardiac Atrial Electrical Activity during Development

    Czech Academy of Sciences Publication Activity Database

    Tenin, G.; Clowes, Ch.; Wolton, K.; Krejčí, Eliška; Wright, J. A.; Lovell, S. C.; Sedmera, David; Hentges, K. E.

    2014-01-01

    Roč. 9, č. 9 (2014), e107041 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA13-12412S; GA ČR(CZ) GAP302/11/1308 Institutional support: RVO:67985823 Keywords : mouse * embryo * atrium * conduction * optical mapping * ENU mutagenesis Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.234, year: 2014

  15. ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

    OpenAIRE

    Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I.; Creighton, Chad J.; Kheradmand, Farrah; DeMayo, Francesco J.

    2015-01-01

    Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 resul...

  16. Role of Stat3 and ErbB2 in Breast Cancer

    Science.gov (United States)

    2013-12-01

    Nemoto, K.E. Pestell , K. Cooley, E.C. Southwick, D.A. Mitchell, W. Furey, R. Gussio, D.W. Zaharevitz, B. Joo, P. Wipf, Identification of a potent...7). Inorg Chem 2008, 47:2798–2804. 26. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al: Stat3 as an oncogene. Cell...Biochem Biophys Res Commun 382: 440-444, 2009. 7 Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C and Darnell JE Jr.: Stat3 as an

  17. Role of Stat3 and ErbB2 in Breast Cancer

    Science.gov (United States)

    2011-10-01

    49631-49637 (2002). 35. Razani,B. et al. Caveolin-1 expression is down-regulated in cells transformed by the human papilloma virus in a p53...polio vaccines, whose prevalence in humans is not clear (Garcea and Imperiale, 2003). The response of cultured cells to DNA tumor virus infection... human papilloma viruses 16 and 18 have been implicated in the development of epithelial malignancies, especially cancer of the uterine cervix and other

  18. High Energy Single Frequency Resonant Amplifier, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR phase I project proposes a single frequency high energy resonant amplifier for remote sensing. Current state-of-art technologies can not provide all...

  19. Distributed CMOS Bidirectional Amplifiers Broadbanding and Linearization Techniques

    CERN Document Server

    El-Khatib, Ziad; Mahmoud, Samy A

    2012-01-01

    This book describes methods to design distributed amplifiers useful for performing circuit functions such as duplexing, paraphrase amplification, phase shifting power splitting and power combiner applications.  A CMOS bidirectional distributed amplifier is presented that combines for the first time device-level with circuit-level linearization, suppressing the third-order intermodulation distortion. It is implemented in 0.13μm RF CMOS technology for use in highly linear, low-cost UWB Radio-over-Fiber communication systems. Describes CMOS distributed amplifiers for optoelectronic applications such as Radio-over-Fiber systems, base station transceivers and picocells; Presents most recent techniques for linearization of CMOS distributed amplifiers; Includes coverage of CMOS I-V transconductors, as well as CMOS on-chip inductor integration and modeling; Includes circuit applications for UWB Radio-over-Fiber networks.

  20. Optical crosstalk reduction using Amplified Spontaneous Emission (ASE)

    NARCIS (Netherlands)

    Chen, H.; Fontaine, N.K.; Ryf, R.; Alvarado, J.C.; van Weerdenburg, J.A.A.; Amezcua-Correa, R.; Okonkwo, C.; Koonen, A.M.J.

    2018-01-01

    We employ spectrally filtered amplified spontaneous emission as the signal carrier and matched local oscillator to mitigate optical crosstalk. We demonstrate polarization crosstalk reduction in single-mode fiber transmission and modal crosstalk reduction over multimode fiber.

  1. Waveguide source of amplified spontaneous emission ASE 1550 nm

    International Nuclear Information System (INIS)

    Razik, M.; Budnicki, A.; Abramski, M.

    2003-01-01

    Light source of amplified spontaneous emission (ASE) type has been built on the base of double-clad waveguide doped with ytterbium and erbium. The characteristics and applications of the ASE source have been also presented

  2. Directional amplifier in an optomechanical system with optical gain

    Science.gov (United States)

    Jiang, Cheng; Song, L. N.; Li, Yong

    2018-05-01

    Directional amplifiers are crucial nonreciprocal devices in both classical and quantum information processing. Here we propose a scheme for realizing a directional amplifier between optical and microwave fields based on an optomechanical system with optical gain, where an active optical cavity and two passive microwave cavities are coupled to a common mechanical resonator via radiation pressure. The two passive cavities are coupled via hopping interaction to facilitate the directional amplification between the active and passive cavities. We obtain the condition of achieving optical directional amplification and find that the direction of amplification can be controlled by the phase differences between the effective optomechanical couplings. The effects of the gain rate of the active cavity and the effective coupling strengths on the maximum gain of the amplifier are discussed. We show that the noise added to this amplifier can be greatly suppressed in the large cooperativity limit.

  3. Characterization and Optimization of the Magnetron Directional Amplifier

    National Research Council Canada - National Science Library

    Hatfield, Michael

    1999-01-01

    .... A conventional microwave oven magnetron may be converted into a two-port amplifier capable of delivering over 30 dB of gain, while remaining phase-locked to the input signal over a wide frequency range...

  4. High power X-band coaxial amplifier experiments

    International Nuclear Information System (INIS)

    Davis, T.J.; Nation, J.A.

    1991-01-01

    Studies are continuing on the development of X-band coaxial microwave amplifiers as a source for next generation linear colliders. Coaxial amplifiers employ an annular electron beam propagating between inner and outer drift tube conductors, a configuration which allows large increases in beam current over standard pencil beam amplifiers. Large average diameter systems may still be used without mode competition since TM mode cutoff frequencies are controlled by the separation between conductors. A number of amplifier configurations are being studied, all primed by a driven initial cavity which resonates around 9 GHz. Simple theory of coaxial systems and particle-in-cell simulations are presented, as well as initial experimental results using a 420 keV, 7-8 kA, 9 cm diameter annular beam

  5. Pole-zero adjustment of spectroscopy amplifiers using multichannel analyzers

    Energy Technology Data Exchange (ETDEWEB)

    Ianakiev, K; Grigorov, T [Inst. for Nuclear Research and Nuclear Energy, Sofia (Bulgaria)

    1996-12-31

    The technique to eliminate the undesirable undershoot in the output signal of a spectroscopy amplifier is considered. The functional scheme of the pole-zero monitoring circuit is presented as well as its operation principles are considered. 3 refs.

  6. Free-electron laser system with Raman amplifier outcoupling

    Energy Technology Data Exchange (ETDEWEB)

    Linford, G.J.

    1988-05-03

    A free-electron laser system is described comprising: a free-electron laser pump beam generator producing a high-power optical output beam in a vacuum environement; a Raman amplifier cell located in the path of the output beam from the pump beam generator; means for generating and introducing a Stokes seed beam into the Raman amplifier cell, a pair of gaseous windows through which the output beam enters and leaves the Raman amplifier cell, each window having a stream of gas moving continuously in a direction generally perpendicular to the beam; and a mirror positioned in the path of the output beam from the Raman amplifier, the mirror functioning to reflect and further direct the output beam, but not the unwanted spectral components.

  7. Rare-Earth Doped Photonic Crystal Fibre Lasers and Amplifiers

    DEFF Research Database (Denmark)

    Hougaard, Kristian G.

    2005-01-01

    In this thesis, a theoretical and numerical study of the use of rare-earthdoped photonic crystal fibres as optical amplifiers and lasers, has been performed. Photonic crystal fibres or microstructured optical fibres is a new kind of optical fibre in which the cladding region typically consist....... Their novel properties allow for design of optical fibre amplifiers and fibre lasers with superior performance, compared to solutions based on conventional fibres. The primary applications considered are high efficiency fibre amplifiers based on index guiding photonic crystal fibres, and cladding pumped....... The thesis also presents the basic properties of optical amplification, and describes the numerical model developed to model the behaviour of lasers and amplifiers based on photonic crystal fibres. The developed numerical tools are then used to investigate specific applications of photonic crystal fibres...

  8. Fiber amplifiers under thermal loads leading to transverse mode instability

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Hansen, Kristian Rymann; Alkeskjold, Thomas Tanggaard

    2014-01-01

    Transverse mode instability (TMI) in rare-earth doped fiber amplifiers operating above an average power threshold is caused by intermodal stimulated thermal Rayleigh scattering due to quantum defect heating. We investigate thermally induced longitudinal waveguide perturbations causing power...

  9. Programmable gain equalizer for multi-core fiber amplifiers

    NARCIS (Netherlands)

    Fontaine, N.K.; Guan, B.; Ryf, R.; Chen, H.; Koonen, A.M.J.; Ben Yoo, S.J.; Abedin, K.; Fini, J.; Taunay, T.F.; Neilson, D.T.

    2014-01-01

    We demonstrate a programmable gain equalizer for 7-core fiber that can independently equalize spectra or block wavelengths in each core across the C-band. It is spliced directly to a side-pumped multi-core amplifying fiber.

  10. Parametric Amplifiers for Microwave Kinectic Inductance Detector (MKID) Readout

    Data.gov (United States)

    National Aeronautics and Space Administration — Build a microwave amplifier with near quantum-limited sensitivity, octave or greater bandwidth, gain > 20 dB for input signals in the frequency range 1 – 10 GHz,...

  11. Development of microwave amplifier based on gallium nitride semiconductor structures

    International Nuclear Information System (INIS)

    Pavlov, D.Yi.; Prokopenko, O.V.; Tsvyirko, Yu.A.; Pavlov, Yi.L.

    2014-01-01

    Microwave properties of microwave amplifier based on gallium nitride (GN) semiconductor structures has been calculated numerically. We proposed the method of numerical calculation of device. This method is accurately sets the value of its characteristics depending on the elements that are used in design of amplifier. It is shown that the device based on GN HEMT-transistors could have amplification factor about 50 dB, while its sizes are 27x18x5.5 mm 3 . Also was provided the absolute stability an amplifier in the whole operating frequency range. It is quite important when using this type of amplifiers in different conditions of exploitation and various fields of use the radioelectronic equipment

  12. Ka-Band Klystron Amplifier for CUBESATs, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — We offer an ultra-compact klystron amplifier for remote sensing on CubeSats. It will operate at 35.7 GHz, have 400 MHz bandwidth, and output greater than 32 watts...

  13. On the unlimited gain of a nonlinear parametric amplifier

    DEFF Research Database (Denmark)

    Sorokin, Vladislav

    2014-01-01

    The present paper is concerned with analysis of the response of a nonlinear parametric amplifier in abroad range of system parameters, particularly beyond resonance. Such analysis is of particular interestfor micro- and nanosystems, since many small-scale parametric amplifiers exhibit a distinctly...... nonlinearbehavior when amplitude of their response is sufficiently large. The modified method of direct separa-tion of motions is employed to study the considered system. As the result it is obtained that steady-stateamplitude of the nonlinear parametric amplifier response can reach large values in the case...... of arbitrarilysmall amplitude of external excitation, so that the amplifier gain tends to infinity. Very large amplifiergain can be achieved in a broad range of system parameters, in particular when the amplitude of para-metric excitation is comparatively small. The obtained results clearly demonstrate that very...

  14. Hearing Aids and Personal Sound Amplifiers: Know the Difference

    Science.gov (United States)

    ... Products For Consumers Home For Consumers Consumer Updates Hearing Aids and Personal Sound Amplifiers: Know the Difference ... that FDA launched today. Signs of Loss of Hearing Mann says that consumers who suspect they suffer ...

  15. Effects of entanglement in an ideal optical amplifier

    Science.gov (United States)

    Franson, J. D.; Brewster, R. A.

    2018-04-01

    In an ideal linear amplifier, the output signal is linearly related to the input signal with an additive noise that is independent of the input. The decoherence of a quantum-mechanical state as a result of optical amplification is usually assumed to be due to the addition of quantum noise. Here we show that entanglement between the input signal and the amplifying medium can produce an exponentially-large amount of decoherence in an ideal optical amplifier even when the gain is arbitrarily close to unity and the added noise is negligible. These effects occur for macroscopic superposition states, where even a small amount of gain can leave a significant amount of which-path information in the environment. Our results show that the usual input/output relation of a linear amplifier does not provide a complete description of the output state when post-selection is used.

  16. A Cost-Effective Amplifier for Electromagnetic Field Strength Measurement

    National Research Council Canada - National Science Library

    Rusek, A

    2001-01-01

    .... This paper presents an inexpensive broadband amplifier designed to increase the overall gain of a measurement system consisting of a 50 ohm broadband antenna coupled to a 50 ohm input spectrum analyzer...

  17. Amplifying mirrors with saturated gain without and with a resonator

    DEFF Research Database (Denmark)

    Skettrup, Torben

    2007-01-01

    An investigation of amplifying mirrors with a view to their use in resonator structures has been performed. Both non-saturated and saturated amplifying mirrors are demonstrated. It was found that relatively high values of gain (typical 5-10 times) can be obtained even when saturation is taken...... into account. Several resonator structures containing from two up to four mirrors, some including beamsplitters, are investigated. It was found that the gain to a first approximation depends only on the ratio between the pumping power and the input power on the amplifying mirror. It was also found...... that the configuration with four mirrors is well suited as an amplifier device working as an optical transistor since high values of gain up to 40 times could be obtained....

  18. Wideband multi-element Er-doped fiber amplifier

    International Nuclear Information System (INIS)

    Thipparapu, N K; Jain, S; May-Smith, T C; Sahu, J K

    2014-01-01

    A multi-element Er-doped fiber amplifier (MEEDFA) is demonstrated in which the gain profile is extended into the S and L bands. Each fiber element of the MEEDFA is found to provide a maximum gain of 37 dB and a noise figure of < 4 dB in the C-band. The gain profile of the amplifier is shifted towards longer wavelength by cascading fiber elements. The novel geometry of the multi-element fiber (MEF) could allow for the development of a broadband amplifier in a split-band configuration. The proposed amplifier can operate in the wavelength band of 1520 to 1595 nm (75 nm), with a minimum gain of 20 dB. (letter)

  19. Amplifiers with ground-isolated inputs and outputs

    International Nuclear Information System (INIS)

    Da Costa Vieira, David; Merite, Bernard; Tattegrain, Alain

    1969-06-01

    The amplifiers described in this note aim at ensuring a connection between different apparatuses with grounds being at a different potential. They will be inserted in the measurement channels of the Cabri reactor

  20. induced by cadmium using random amplified polymorphic DNA

    African Journals Online (AJOL)

    darya

    2013-04-17

    Apr 17, 2013 ... metallurgy, painting, plastic production, etc., and is being released into the biosphere, and ...... aquatic macrophytes: Random amplified polymorphic DNA analysis and identification of ... ecotoxicology. Toxicol. Ecotoxicol.

  1. High Efficiency S-Band 20 Watt Amplifier

    Data.gov (United States)

    National Aeronautics and Space Administration — This project includes the design and build of a prototype 20 W, high efficiency, S-Band amplifier.   The design will incorporate the latest semiconductor technology,...

  2. Resistor-less charge sensitive amplifier for semiconductor detectors

    Energy Technology Data Exchange (ETDEWEB)

    Pelczar, K., E-mail: krzysztof.pelczar@doctoral.uj.edu.pl; Panas, K.; Zuzel, G.

    2016-11-01

    A new concept of a Charge Sensitive Amplifier without a high-value resistor in the feedback loop is presented. Basic spectroscopic parameters of the amplifier coupled to a coaxial High Purity Germanium detector (HPGe) are discussed. The amplifier signal input is realized with an n-channel J-FET transistor. The feedback capacitor is discharged continuously by the second, forward biased n-channel J-FET, driven by an RC low–pass filter. Both the analog—with a standard spectroscopy amplifier and a multi-channel analyzer—and the digital—by applying a Flash Analog to Digital Converter—signal readouts were tested. The achieved resolution in the analog and the digital readouts was 0.17% and 0.21%, respectively, at the Full Width at Half Maximum of the registered {sup 60}Co 1332.5 keV gamma line.

  3. Linear and nonlinear analysis of high-power rf amplifiers

    International Nuclear Information System (INIS)

    Puglisi, M.

    1983-01-01

    After a survey of the state variable analysis method the final amplifier for the CBA is analyzed taking into account the real beam waveshape. An empirical method for checking the stability of a non-linear system is also considered

  4. Ferrite bead effect on Class-D amplifier audio quality

    OpenAIRE

    Haddad , Kevin El; Mrad , Roberto; Morel , Florent; Pillonnet , Gael; Vollaire , Christian; Nagari , Angelo

    2014-01-01

    International audience; This paper studies the effect of ferrite beads on the audio quality of Class-D audio amplifiers. This latter is a switch-ing circuit which creates high frequency harmonics. Generally, a filter is used at the amplifier output for the sake of electro-magnetic compatibility (EMC). So often, in integrated solutions, this filter contains ferrite beads which are magnetic components and present nonlinear behavior. Time domain measurements and their equivalence in frequency do...

  5. Ripple compensation for a class-D amplifier

    OpenAIRE

    Cox, Stephen M.; du Toit Mouton, Hendrik

    2015-01-01

    This paper presents the first detailed mathematical analysis of the ripple compensation technique for reducing audio distortion in a class-D amplifier with negative feedback. The amplifier converts a relatively low-frequency audio signal to a high-frequency train of rectangular pulses whose widths are slowly modulated according to the audio signal (pulse-width modulation, PWM). Distortion manifests itself through unwanted audio-frequency harmonics that arise in the output due to nonlinearitie...

  6. An amplifier for VUV photomultiplier operating in cryogenic environment

    International Nuclear Information System (INIS)

    Arneodo, F.; Benabderrahmane, M.L.; Dahal, S.; Di Giovanni, A.; D'Inzeo, M.; Franchi, G.; Pazos Clemens, L.

    2016-01-01

    We present the characterisation of an amplifier potentially interesting for noble liquid detectors. The design has been conceived considering the requirements of low power consumption (less than 30 mW), low noise, amplification factor of 10 at 100 MHz and use of commercial components. The amplifier has been integrated onto an electronic board with a voltage divider to operate an Hamamatsu R11410 photomultiplier tube (used in XENON1T, Aprile et al. (2014) [1] dark matter experiment).

  7. An amplifier for VUV photomultiplier operating in cryogenic environment

    Energy Technology Data Exchange (ETDEWEB)

    Arneodo, F.; Benabderrahmane, M.L.; Dahal, S. [New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Di Giovanni, A., E-mail: adriano.digiovanni@nyu.edu [New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); D' Inzeo, M.; Franchi, G. [Age Scientific srl – Capezzano Pianore (Italy); Pazos Clemens, L. [New York University Abu Dhabi, Abu Dhabi (United Arab Emirates)

    2016-07-11

    We present the characterisation of an amplifier potentially interesting for noble liquid detectors. The design has been conceived considering the requirements of low power consumption (less than 30 mW), low noise, amplification factor of 10 at 100 MHz and use of commercial components. The amplifier has been integrated onto an electronic board with a voltage divider to operate an Hamamatsu R11410 photomultiplier tube (used in XENON1T, Aprile et al. (2014) [1] dark matter experiment).

  8. Design of low noise transimpedance amplifier for intravascular ultrasound

    KAUST Repository

    Reda, Dina

    2009-11-01

    In this paper, we study transimpedance amplifiers for capacitive sensing applications with a focus on Intravascular Ultra Sound (IVUS). We employ RF noise cancellation technique on capacitive feedback based transimpedance amplifiers. This technique eliminates the input-referred noise of TIAs completely and enhances the dynamic range of front-end electronics. Simulation results verify the proposed technique used in two different TIA topologies employing shunt-shunt feedback. ©2009 IEEE.

  9. Remote optically-tunable transimpedance amplifiers for quantum well diodes

    Energy Technology Data Exchange (ETDEWEB)

    Carraresi, L.; Landi, G.; Rocchi, S.; Vignoli, V

    1999-08-01

    In a previous paper we discussed the advantages in using linear optical transmission systems based on quantum well diodes in modern high energy physics experiments. In this paper, after a short summary of the quantum well theory, the electronics section of the above optical transmission system is presented. In particular the basic configuration of a transimpedance amplifier and the arrangement of an optical remote control system for the amplifier gain and bandwidth tuning are discussed.

  10. Remote optically-tunable transimpedance amplifiers for quantum well diodes

    International Nuclear Information System (INIS)

    Carraresi, L.; Landi, G.; Rocchi, S.; Vignoli, V.

    1999-01-01

    In a previous paper we discussed the advantages in using linear optical transmission systems based on quantum well diodes in modern high energy physics experiments. In this paper, after a short summary of the quantum well theory, the electronics section of the above optical transmission system is presented. In particular the basic configuration of a transimpedance amplifier and the arrangement of an optical remote control system for the amplifier gain and bandwidth tuning are discussed

  11. An analog integrated front-end amplifier for neural applications

    OpenAIRE

    Zhou, Zhijun; Warr, Paul

    2017-01-01

    The front-end amplifier forms the critical element for signal detection and pre-processing within neural monitoring systems. It determines not only the fidelity of the biosignal, but also impacts power consumption and detector size. In this paper, a combined feedback loop-controlled approach is proposed to neutralize for the input leakage currents generated by low noise amplifiers when in integrated circuit form, alongside signal leakage into the input bias network. Significantly, this loop t...

  12. Progress on the gyrocon deflection-modulated amplifier

    International Nuclear Information System (INIS)

    Tallerico, P.J.

    1982-01-01

    The gyrocon is a high-power deflection-modulated amplifier that can have excellent spatial bunching and, hence, high dc-to-rf conversion efficiency. A program to design and build a prototype amplifier at 450 MHz is discussed. Peak powers of 150 kW and conversion efficiencies of 23% have been measured; the testing program is being pursued to improve this performance. Some possible mechanisms for the difference between the experimental and calculated performance are discussed

  13. Ultrafast optical signal processing using semiconductor quantum dot amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper

    2002-01-01

    The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing.......The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing....

  14. Self-amplifying autocrine actions of BDNF in axon development

    OpenAIRE

    Cheng, Pei-Lin; Song, Ai-Hong; Wong, Yu-Hui; Wang, Sheng; Zhang, Xiang; Poo, Mu-Ming

    2011-01-01

    A critical step in neuronal development is the formation of axon/dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine f...

  15. A high-power compact regenerative amplifier FEL

    International Nuclear Information System (INIS)

    Nguyen, D.C.; Sheffield, R.L.; Fortgang, C.M.; Kinross-Wright, J.M.; Ebrahim, N.A.; Goldstein, J.C.

    1997-01-01

    The Regenerative Amplifier FEL (RAFEL) is a new FEL approach aimed at achieving the highest optical power from a compact rf-linac FEL. The key idea is to feed back a small fraction ( 5 in single pass) wiggler to enable the FEL to reach saturation in a few passes. This paper summarizes the design of a high-power compact regenerative amplifier FEL and describes the first experimental demonstration of the RAFEL concept

  16. Design And Construction Of 300W Audio Power Amplifier For Classroom

    Directory of Open Access Journals (Sweden)

    Shune Lei Aung

    2015-07-01

    Full Text Available Abstract This paper describes the design and construction of 300W audio power amplifier for classroom. In the construction of this amplifier microphone preamplifier tone preamplifier equalizer line amplifier output power amplifier and sound level indicator are included. The output power amplifier is designed as O.C.L system and constructed by using Class B among many types of amplifier classes. There are two types in O.C.L system quasi system and complementary system. Between them the complementary system is used in the construction of 300W audio power amplifier. The Multisim software is utilized for the construction of audio power amplifier.

  17. Photonic-band-gap gyrotron amplifier with picosecond pulses

    Science.gov (United States)

    Nanni, Emilio A.; Jawla, Sudheer; Lewis, Samantha M.; Shapiro, Michael A.; Temkin, Richard J.

    2017-12-01

    We report the amplification of 250 GHz pulses as short as 260 ps without observation of pulse broadening using a photonic-band-gap circuit gyrotron traveling-wave-amplifier. The gyrotron amplifier operates with a device gain of 38 dB and an instantaneous bandwidth of 8 GHz. The operational bandwidth of the amplifier can be tuned over 16 GHz by adjusting the operating voltage of the electron beam and the magnetic field. The amplifier uses a 30 cm long photonic-band-gap interaction circuit to confine the desired TE03-like operating mode while suppressing lower order modes which can result in undesired oscillations. The circuit gain is >55 dB for a beam voltage of 23 kV and a current of 700 mA. These results demonstrate the wide bandwidths and a high gain achievable with gyrotron amplifiers. The amplification of picosecond pulses of variable lengths, 260-800 ps, shows good agreement with the theory using the coupled dispersion relation and the gain-spectrum of the amplifier as measured with quasi-CW input pulses.

  18. Power Amplifier Design for E-band Wireless System Communications

    DEFF Research Database (Denmark)

    Hadziabdic, Dzenan; Krozer, Viktor; Johansen, Tom Keinicke

    2008-01-01

    E-band wireless communications will become important as the microwave backhaul for high-speed data transmission. One of the most critical components is the front-end power amplifier in this system. The paper analyzes different technologies with potential in the E-band frequency range and present...... a power amplifier design satisfying the E-band system specifications. The designed power amplifier achieves a maximum output power of ges 20 dBm with a state-of-the-art power-added efficiency of 15%. The power is realized using InP DHBT technology. To the best of our knowledge it is the highest output...... power and efficiency reported for an InP HBT power amplifier in this frequency range. The predicted power-added efficiency is higher than that of power amplifiers based on SiGe HBT and GaAs pHEMT technologies. The design shows the capabilities of InP DHBT for power amplifier applications...

  19. AlGaN/GaN-HEMT power amplifiers with optimized power-added efficiency for X-band applications

    OpenAIRE

    Kühn, J.

    2011-01-01

    This work has arisen out of the strong demand for a superior power-added efficiency (PAE) of AlGaN/GaN high electron mobility transistor (HEMT) high-power amplifiers (HPAs) that are part of any advanced wireless multifunctional RF-system with limited prime energy. Different concepts and approaches on device and design level for PAE improvements are analyzed, e.g. structural and layout changes of the GaN transistor and advanced circuit design techniques for PAE improvements of GaN HEMT HPAs.

  20. Redox cycling-based amplifying electrochemical sensor for in situ clozapine antipsychotic treatment monitoring

    International Nuclear Information System (INIS)

    Ben-Yoav, Hadar; Winkler, Thomas E.; Kim, Eunkyoung; Chocron, Sheryl E.; Kelly, Deanna L.; Payne, Gregory F.; Ghodssi, Reza

    2014-01-01

    Highlights: • A new concept for clozapine in situ sensing with minimal pre-treatment procedures. • A catechol-chitosan redox cycling system amplifies clozapine oxidation current. • The modified amplifier signal is 3 times greater than the unmodified system. • Differentiation between clozapine and its metabolite norclozapine has been shown. • The sensor has the capability to detect clozapine in human serum. - Abstract: Schizophrenia is a lifelong mental disorder with few recent advances in treatment. Clozapine is the most effective antipsychotic for schizophrenia treatment. However, it remains underutilized since frequent blood draws are required to monitor adverse side effects, and maintain clozapine concentrations in a therapeutic range. Micro-system technology utilized towards real-time monitoring of efficacy and safety will enable personalized medicine and better use of this medication. Although work has been reported on clozapine detection using its electrochemical oxidation, no in situ monitoring of clozapine has been described. In this work, we present a new concept for clozapine in situ sensing based on amplifying its oxidation current. Specifically, we use a biofabricated catechol-modified chitosan redox cycling system to provide a significant amplification of the generated oxidizing current of clozapine through a continuous cycle of clozapine reduction followed by re-oxidation. The amplified signal has improved the signal-to-noise ratio and provided the required limit-of-detection and dynamic range for clinical applications with minimal pre-treatment procedures. The sensor reports on the functionality and sensitivity of clozapine detection between 0.1 and 10 μg/mL. The signal generated by clozapine using the catechol-modified chitosan amplifier has shown to be 3 times greater than the unmodified system. The sensor has the ability to differentiate between clozapine and its metabolite norclozapine, as well as the feasibility to detect clozapine in

  1. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    Science.gov (United States)

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  2. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

    Science.gov (United States)

    Robarts, Daniel W H; Wolfe, Andrea D

    2014-07-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

  3. High power rf amplifiers for accelerator applications: The large orbit gyrotron and the high current, space charge enhanced relativistic klystron

    International Nuclear Information System (INIS)

    Stringfield, R.M.; Fazio, M.V.; Rickel, D.G.; Kwan, T.J.T.; Peratt, A.L.; Kinross-Wright, J.; Van Haaften, F.W.; Hoeberling, R.F.; Faehl, R.; Carlsten, B.; Destler, W.W.; Warner, L.B.

    1991-01-01

    Los Alamos is investigating a number of high power microwave (HPM) sources for their potential to power advanced accelerators. Included in this investigation are the large orbit gyrotron amplifier and oscillator (LOG) and the relativistic klystron amplifier (RKA). LOG amplifier development is newly underway. Electron beam power levels of 3 GW, 70 ns duration, are planned, with anticipated conversion efficiencies into RF on the order of 20 percent. Ongoing investigations on this device include experimental improvement of the electron beam optics (to allow injection of a suitable fraction of the electron beam born in the gun into the amplifier structure), and computational studies of resonator design and RF extraction. Recent RKA studies have operated at electron beam powers into the device of 1.35 GW in microsecond duration pulses. The device has yielded modulated electron beam power approaching 300 MW using 3-5 kW of RF input drive. RF powers extracted into waveguide have been up to 70 MW, suggesting that more power is available from the device than has been converted to-date in the extractor

  4. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

    International Nuclear Information System (INIS)

    Mackenzie, Robertson; Kommoss, Stefan; Winterhoff, Boris J.; Kipp, Benjamin R.; Garcia, Joaquin J.; Voss, Jesse; Halling, Kevin; Karnezis, Anthony; Senz, Janine; Yang, Winnie; Prigge, Elena-Sophie; Reuschenbach, Miriam; Doeberitz, Magnus Von Knebel; Gilks, Blake C.; Huntsman, David G.; Bakkum-Gamez, Jamie; McAlpine, Jessica N.; Anglesio, Michael S.

    2015-01-01

    populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event. Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway “double-hits” supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations. The online version of this article (doi:10.1186/s12885-015-1421-8) contains supplementary material, which is available to authorized users

  5. Ways to suppress click and pop for class D amplifiers

    International Nuclear Information System (INIS)

    Wang Haishi; Zhang Bo; Sun Jiang

    2012-01-01

    Undesirable audio click and pop may be generated in a speaker or headphone. Compared to linear (class A/B/AB) amplifiers, class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop. This article analyzes sources that generate click and pop in class D amplifiers, and corresponding ways to suppress them. For a class D amplifier with a single-ended input, click and pop is likely to be due to two factors. One is from a voltage difference (V DIF ) between the voltage of an input capacitance (V CIN ) and a reference voltage (V REF ) of the input stage, and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage. In this article, a fast charging loop is introduced into the input stage to charge V CIN to roughly near V REF . Then a correction loop further charges or discharges V CIN , substantially equalizing it with V REF . Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC, and the power switches are disabled until the BFVC are set up successfully. A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process. Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop. (semiconductor integrated circuits)

  6. Amplified spontaneous emission measurements on the Aurora large aperture module

    International Nuclear Information System (INIS)

    Oertel, J.A.; Czuchlewski, S.J.; Leland, W.T.; Turner, T.P.

    1990-01-01

    The large aperture module (LAM) of the Aurora KrF laser can be used to address a number of issues that relate to the scaling of KrF amplifiers to larger ICF systems. Perhaps foremost among these are the possible effects of amplified spontaneous emission (ASE) on laser performance. To assess this problem a 3-D computer code has been developed to model these ASE effects. The code uses an iterative procedure to arrive at a self-consistent steady state solution to the 3-D distribution of coherent and incoherent fluxes within the amplifier. Two-pass energy extraction, wall reflectivity, and nonuniform excitation are included in the model. The authors previously reported the effects of ASE on the small signal gains measured in the 1- x 1- x 2-m 3 LAM. The code also makes quantitative predictions of the ASE that should be generated in the amplifier. This paper indicates the radiance expected for a medium of uniform gain in terms of the (g - ν)L product and the parameter g/a. The quantity (g - ν)L is the product of the net gain and the path length along the direction of observation. The present experiments compare values of ASE measured at various locations around the LAM with the code predictions. The impact of ASE on amplifier output, is also discussed

  7. Power neodymium-glass amplifier of a repetitively pulsed laser

    Energy Technology Data Exchange (ETDEWEB)

    Vinogradov, Aleksandr V; Gaganov, V E; Garanin, Sergey G; Zhidkov, N V; Krotov, V A; Martynenko, S P; Pozdnyakov, E V; Solomatin, I I [Russian Federal Nuclear Center ' All-Russian Research Institute of Experimental Physics' , Sarov, Nizhnii Novgorod region (Russian Federation)

    2011-11-30

    A neodymium-glass diode-pumped amplifier with a zigzag laser beam propagation through the active medium was elaborated; the amplifier is intended for operation in a repetitively pulsed laser. An amplifier unit with an aperture of 20 Multiplication-Sign 25 mm and a {approx}40-cm long active medium was put to a test. The energy of pump radiation amounts to 140 J at a wavelength of 806 nm for a pump duration of 550 {mu}s. The energy parameters of the amplifier were experimentally determined: the small-signal gain per pass {approx}3.2, the linear gain {approx}0.031 cm{sup -1} with a nonuniformity of its distribution over the aperture within 15%, the stored energy of 0.16 - 0.21 J cm{sup -3}. The wavefront distortions in the zigzag laser-beam propagation through the active element of the amplifier did not exceed 0.4{lambda} ({lambda} = 0.63 {mu}m is the probing radiation wavelength).

  8. Power neodymium-glass amplifier of a repetitively pulsed laser

    International Nuclear Information System (INIS)

    Vinogradov, Aleksandr V; Gaganov, V E; Garanin, Sergey G; Zhidkov, N V; Krotov, V A; Martynenko, S P; Pozdnyakov, E V; Solomatin, I I

    2011-01-01

    A neodymium-glass diode-pumped amplifier with a zigzag laser beam propagation through the active medium was elaborated; the amplifier is intended for operation in a repetitively pulsed laser. An amplifier unit with an aperture of 20 × 25 mm and a ∼40-cm long active medium was put to a test. The energy of pump radiation amounts to 140 J at a wavelength of 806 nm for a pump duration of 550 μs. The energy parameters of the amplifier were experimentally determined: the small-signal gain per pass ∼3.2, the linear gain ∼0.031 cm -1 with a nonuniformity of its distribution over the aperture within 15%, the stored energy of 0.16 - 0.21 J cm -3 . The wavefront distortions in the zigzag laser-beam propagation through the active element of the amplifier did not exceed 0.4λ (λ = 0.63 μm is the probing radiation wavelength).

  9. Spectroscopic amplifier for pin diode; Amplificador espectroscopico para diodo Pin

    Energy Technology Data Exchange (ETDEWEB)

    Alonso M, M. S.; Hernandez D, V. M.; Vega C, H. R., E-mail: bebe.luna_s@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

    2014-10-15

    The photodiode remains the basic choice for the photo-detection and is widely used in optical communications, medical diagnostics and field of corpuscular radiation. In detecting radiation it has been used for monitoring radon and its progeny and inexpensive spectrometric systems. The development of a spectroscopic amplifier for Pin diode is presented which has the following characteristics: canceler Pole-Zero (P/Z) with a time constant of 8 μs; constant gain of 57, suitable for the acquisition system; 4th integrator Gaussian order to waveform change of exponential input to semi-Gaussian output and finally a stage of baseline restorer which prevents Dc signal contribution to the next stage. The operational amplifier used is the TLE2074 of BiFET technology of Texas Instruments with 10 MHz bandwidth, 25 V/μs of slew rate and a noise floor of 17 nv/(Hz)1/2. The integrated circuit has 4 operational amplifiers and in is contained the total of spectroscopic amplifier that is the goal of electronic design. The results show like the exponential input signal is converted to semi-Gaussian, modifying only the amplitude according to the specifications in the design. The total system is formed by the detector, which is the Pin diode, a sensitive preamplifier to the load, the spectroscopic amplifier that is what is presented and finally a pulse height analyzer (Mca) which is where the spectrum is shown. (Author)

  10. GAME EDUKASI PERAKITAN AMPLIFIER BERBASIS ANDROID UNTUK USER UMUM

    Directory of Open Access Journals (Sweden)

    Fundhi Fanju Hafili

    2015-04-01

    Full Text Available ABSTRAK Seiring dengan perkembangan dan kebutuhan teknologi saat ini pembelajaran elektro dapat dibuat menjadi lebih praktis dan menarik di ponsel berbasis android Mempelajari elektronika juga memerlukan usaha-usaha nyata yang ber-kesinambungan dan mengarah kepada tumbuhnya kesadaran untuk menjadikan elektronika sebagai perkembangan teknologi. Dengan adanya metode game, merupakan salah satu metode belajar merakit amplifier yang disusun secara praktis dan sistematis sehingga memudahkan setiap orang untuk belajar maupun mengajarkan merancang amplifier. Sementara itu metode pembelajaran yang ada saat ini yaitu melalui buku maupun dengan cara bertatap muka langsung dengan tentor dirasa masih kurang efektif. Untuk mengatasi masalah tersebut maka penulis membuat game edukasi elektro merancang amplifier, karena mudah dipahami dan memudahkan para calon teknisi elektro dalam belajar merancang amplifier. Perancangan ini dilakukan dengan pendekatan metode Research and Development adalah metode penelitian yang digunakan untuk menghasilkan produk tertentu dan menguji keefektifan produk tersebut. Dengan aplikasi ini diharapkan dapat membantu para pengguna yang ingin belajar merakit amplifier berbasis android. . Kata kunci: elektro, game, research and development.

  11. Integrated circuit amplifiers for multi-electrode intracortical recording.

    Science.gov (United States)

    Jochum, Thomas; Denison, Timothy; Wolf, Patrick

    2009-02-01

    Significant progress has been made in systems that interpret the electrical signals of the brain in order to control an actuator. One version of these systems senses neuronal extracellular action potentials with an array of up to 100 miniature probes inserted into the cortex. The impedance of each probe is high, so environmental electrical noise is readily coupled to the neuronal signal. To minimize this noise, an amplifier is placed close to each probe. Thus, the need has arisen for many amplifiers to be placed near the cortex. Commercially available integrated circuits do not satisfy the area, power and noise requirements of this application, so researchers have designed custom integrated-circuit amplifiers. This paper presents a comprehensive survey of the neural amplifiers described in publications prior to 2008. Methods to achieve high input impedance, low noise and a large time-constant high-pass filter are reviewed. A tutorial on the biological, electrochemical, mechanical and electromagnetic phenomena that influence amplifier design is provided. Areas for additional research, including sub-nanoampere electrolysis and chronic cortical heating, are discussed. Unresolved design concerns, including teraohm circuitry, electrical overstress and component failure, are identified.

  12. Design and development of digital seismic amplifier recorder

    Energy Technology Data Exchange (ETDEWEB)

    Samsidar, Siti Alaa; Afuar, Waldy; Handayani, Gunawan, E-mail: gunawanhandayani@gmail.com [Department of Physics, ITB (Indonesia)

    2015-04-16

    A digital seismic recording is a recording technique of seismic data in digital systems. This method is more convenient because it is more accurate than other methods of seismic recorders. To improve the quality of the results of seismic measurements, the signal needs to be amplified to obtain better subsurface images. The purpose of this study is to improve the accuracy of measurement by amplifying the input signal. We use seismic sensors/geophones with a frequency of 4.5 Hz. The signal is amplified by means of 12 units of non-inverting amplifier. The non-inverting amplifier using IC 741 with the resistor values 1KΩ and 1MΩ. The amplification results were 1,000 times. The results of signal amplification converted into digital by using the Analog Digital Converter (ADC). Quantitative analysis in this study was performed using the software Lab VIEW 8.6. The Lab VIEW 8.6 program was used to control the ADC. The results of qualitative analysis showed that the seismic conditioning can produce a large output, so that the data obtained is better than conventional data. This application can be used for geophysical methods that have low input voltage such as microtremor application.

  13. Low Loss Nanostructured Polymers for Chip-scale Waveguide Amplifiers.

    Science.gov (United States)

    Chen, George F R; Zhao, Xinyu; Sun, Yang; He, Chaobin; Tan, Mei Chee; Tan, Dawn T H

    2017-06-13

    On-chip waveguide amplifiers offer higher gain in small device sizes and better integration with photonic devices than the commonly available fiber amplifiers. However, on-chip amplifiers have yet to make its way into the mainstream due to the limited availability of materials with ideal light guiding and amplification properties. A low-loss nanostructured on-chip channel polymeric waveguide amplifier was designed, characterized, fabricated and its gain experimentally measured at telecommunication wavelength. The active polymeric waveguide core comprises of NaYF 4 :Yb,Er,Ce core-shell nanocrystals dispersed within a SU8 polymer, where the nanoparticle interfacial characteristics were tailored using hydrolyzed polyhedral oligomeric silsesquioxane-graft-poly(methyl methacrylate) to improve particle dispersion. Both the enhanced IR emission intensity from our nanocrystals using a tri-dopant scheme and the reduced scattering losses from our excellent particle dispersion at a high solid loading of 6.0 vol% contributed to the outstanding optical performance of our polymeric waveguide. We achieved one of the highest reported gain of 6.6 dB/cm using a relatively low coupled pump power of 80 mW. These polymeric waveguide amplifiers offer greater promise for integrated optical circuits due to their processability and integration advantages which will play a key role in the emerging areas of flexible communication and optoelectronic devices.

  14. Ways to suppress click and pop for class D amplifiers

    Science.gov (United States)

    Haishi, Wang; Bo, Zhang; Jiang, Sun

    2012-08-01

    Undesirable audio click and pop may be generated in a speaker or headphone. Compared to linear (class A/B/AB) amplifiers, class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop. This article analyzes sources that generate click and pop in class D amplifiers, and corresponding ways to suppress them. For a class D amplifier with a single-ended input, click and pop is likely to be due to two factors. One is from a voltage difference (VDIF) between the voltage of an input capacitance (VCIN) and a reference voltage (VREF) of the input stage, and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage. In this article, a fast charging loop is introduced into the input stage to charge VCIN to roughly near VREF. Then a correction loop further charges or discharges VCIN, substantially equalizing it with VREF. Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC, and the power switches are disabled until the BFVC are set up successfully. A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process. Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop.

  15. 47 CFR 97.315 - Certification of external RF power amplifiers.

    Science.gov (United States)

    2010-10-01

    .... (2) The amplifier was manufactured before April 28, 1978, and has been issued a marketing waiver by... that operator's station. (3) The amplifier is sold to an amateur radio operator or to a dealer, the amplifier is purchased in used condition by a dealer, or the amplifier is sold to an amateur radio operator...

  16. A numerical design approach for single amplifier, Active-RC Butterworth filter of order 5

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    2007-01-01

    filter applying just one operational amplifier coupled as a unity gain amplifier. It is shown that the influence from the real operational amplifier may be reduced by trimming just one resistor in the circuit. The unity gain amplifiers have the advantage of providing low power consumption, yielding...

  17. A Holistic In silico Approach to Develop Novel Inhibitors Targeting ...

    African Journals Online (AJOL)

    Purpose: To design a dual inhibitor of natural origin capable of targeting ErbB1 and ErbB2 kinases for the treatment of lung cancer. Method: Advanced In silico drug designing techniques were explored in this study. Sequence and structure analysis of ErbB1 and ErbB2 was followed by three dimensional (3D) ...

  18. Dynamic absorption coefficients of chemically amplified resists and nonchemically amplified resists at extreme ultraviolet

    Science.gov (United States)

    Fallica, Roberto; Stowers, Jason K.; Grenville, Andrew; Frommhold, Andreas; Robinson, Alex P. G.; Ekinci, Yasin

    2016-07-01

    The dynamic absorption coefficients of several chemically amplified resists (CAR) and non-CAR extreme ultraviolet (EUV) photoresists are measured experimentally using a specifically developed setup in transmission mode at the x-ray interference lithography beamline of the Swiss Light Source. The absorption coefficient α and the Dill parameters ABC were measured with unprecedented accuracy. In general, the α of resists match very closely with the theoretical value calculated from elemental densities and absorption coefficients, whereas exceptions are observed. In addition, through the direct measurements of the absorption coefficients and dose-to-clear values, we introduce a new figure of merit called chemical sensitivity to account for all the postabsorption chemical reaction ongoing in the resist, which also predicts a quantitative clearing volume and clearing radius, due to the photon absorption in the resist. These parameters may help provide deeper insight into the underlying mechanisms of the EUV concepts of clearing volume and clearing radius, which are then defined and quantitatively calculated.

  19. Spatial chirp in Ti:sapphire multipass amplifier

    International Nuclear Information System (INIS)

    Li Wenkai; Lu Jun; Li Yanyan; Guo Xiaoyang; Wu Fenxiang; Yu Linpeng; Wang Pengfei; Xu Yi; Leng Yuxin

    2017-01-01

    The spatial chirp generated in the Ti:sapphire multipass amplifier is numerically investigated based on the one-dimensional (1D) and two-dimensional (2D) Frantz–Nodvik equations. The simulation indicates that the spatial chirp is induced by the spatially inhomogeneous gain, and it can be almost eliminated by utilization of proper beam profiles and spot sizes of the signal and pump pulses, for example, the pump pulse has a top-hatted beam profile and the signal pulse has a super-Gaussian beam profile with a relatively larger spot size. In this way, a clear understanding of spatial chirp mechanisms in the Ti:sapphire multipass amplifier is proposed, therefore we can effectively almost eliminate the spatial chirp and improve the beam quality of a high-power Ti:sapphire chirped pulse amplifier system. (paper)

  20. Efficiency Optimization in Class-D Audio Amplifiers

    DEFF Research Database (Denmark)

    Yamauchi, Akira; Knott, Arnold; Jørgensen, Ivan Harald Holger

    2015-01-01

    This paper presents a new power efficiency optimization routine for designing Class-D audio amplifiers. The proposed optimization procedure finds design parameters for the power stage and the output filter, and the optimum switching frequency such that the weighted power losses are minimized under...... the given constraints. The optimization routine is applied to minimize the power losses in a 130 W class-D audio amplifier based on consumer behavior investigations, where the amplifier operates at idle and low power levels most of the time. Experimental results demonstrate that the optimization method can...... lead to around 30 % of efficiency improvement at 1.3 W output power without significant effects on both audio performance and the efficiency at high power levels....

  1. Embedded control system for high power RF amplifiers

    International Nuclear Information System (INIS)

    Sharma, Deepak Kumar; Gupta, Alok Kumar; Jain, Akhilesh; Hannurkar, P.R.

    2011-01-01

    RF power devices are usually very sensitive to overheat and reflected RF power; hence a protective interlock system is required to be embedded with high power solid state RF amplifiers. The solid state RF amplifiers have salient features of graceful degradation and very low mean time to repair (MTTR). In order to exploit these features in favour of lowest system downtime, a real-time control system is embedded with high power RF amplifiers. The control system is developed with the features of monitoring, measurement and network publishing of various parameters, historical data logging, alarm generation, displaying data to the operator and tripping the system in case of any interlock failure. This paper discusses the design philosophy, features, functions and implementation details of the embedded control system. (author)

  2. Using MEMS Capacitive Switches in Tunable RF Amplifiers

    Directory of Open Access Journals (Sweden)

    Danson John

    2006-01-01

    Full Text Available A MEMS capacitive switch suitable for use in tunable RF amplifiers is described. A MEMS switch is designed, fabricated, and characterized with physical and RF measurements for inclusion in simulations. Using the MEMS switch models, a dual-band low-noise amplifier (LNA operating at GHz and GHz, and a tunable power amplifier (PA at GHz are simulated in m CMOS. MEMS switches allow the LNA to operate with 11 dB of isolation between the two bands while maintaining dB of gain and sub- dB noise figure. MEMS switches are used to implement a variable matching network that allows the PA to realize up to 37% PAE improvement at low input powers.

  3. Multi-path interferometric Josephson directional amplifier for qubit readout

    Science.gov (United States)

    Abdo, Baleegh; Bronn, Nicholas T.; Jinka, Oblesh; Olivadese, Salvatore; Brink, Markus; Chow, Jerry M.

    2018-04-01

    We realize and characterize a quantum-limited, directional Josephson amplifier suitable for qubit readout. The device consists of two nondegenerate, three-wave-mixing amplifiers that are coupled together in an interferometric scheme, embedded in a printed circuit board. Nonreciprocity is generated by applying a phase gradient between the same-frequency pumps feeding the device, which plays the role of the magnetic field in a Faraday medium. Directional amplification and reflection-gain elimination are induced via wave interference between multiple paths in the system. We measure and discuss the main figures of merit of the device and show that the experimental results are in good agreement with theory. An improved version of this directional amplifier is expected to eliminate the need for bulky, off-chip isolation stages that generally separate quantum systems and preamplifiers in high-fidelity, quantum-nondemolition measurement setups.

  4. Electronically Tunable Transimpedance Instrumentation Amplifier Based on OTRA

    Directory of Open Access Journals (Sweden)

    Rajeshwari Pandey

    2013-01-01

    Full Text Available Operational transresistance amplifier (OTRA is the most suitable analog building block (ABB for transimpedance type signal processing due to its very nature of current input and voltage output. In this paper, OTRA-based transimpedance instrumentation amplifier (TIA is presented. It provides high differential gain and bandwidth, which is independent of gain. It also offers high common-mode rejection ratio (CMRR. The amplifier gain can be controlled electronically by implementing resistors using MOS transistors operating in linear region. The circuit can be made fully integrated. The proposed circuit is insensitive to parasitic input capacitances and input resistances due to the internally grounded input terminals of OTRA. Theoretical analysis is verified through PSPICE simulations and experimentation.

  5. A transimpedance amplifier using a novel current mode feedback loop

    CERN Document Server

    Anghinolfi, Francis; Delagnes, E; Jarron, Pierre; Scharfetter, L H H

    1995-01-01

    We present a transimpedance amplifier stage based on a novel current mode feedback topology. This circuit employs NMOS and PMOS transistors exclusively and requires neither capacitor for stabilizing the transimpedance loop nor resistor for the transresistance feedback and transistor loading. This amplifier circuit is fully compatible with submicron digital CMOS processes. The active feedback network consists of two grounded-gate MOS devices which split the output current in both the feedback and output branches. The transresistance and the phase margin are adjustable through external DC signals. The measured rise time of the impulse response of the amplifier implemented in an industrial 0,7µm CMOS process is 18 ns for a transresistance of 180 k‡ and 30 ns for a transresistance of 560 k‡. The measured Equivalent Noise Charge (ENC) is 800 rms e¯ for an input capacitance of 20 pF with the transresistance adjusted to 560 k‡.

  6. A digitally assisted, signal folding neural recording amplifier.

    Science.gov (United States)

    Chen, Yi; Basu, Arindam; Liu, Lei; Zou, Xiaodan; Rajkumar, Ramamoorthy; Dawe, Gavin Stewart; Je, Minkyu

    2014-08-01

    A novel signal folding and reconstruction scheme for neural recording applications that exploits the 1/f(n) characteristics of neural signals is described in this paper. The amplified output is 'folded' into a predefined range of voltages by using comparison and reset circuits along with the core amplifier. After this output signal is digitized and transmitted, a reconstruction algorithm can be applied in the digital domain to recover the amplified signal from the folded waveform. This scheme enables the use of an analog-to-digital convertor with less number of bits for the same effective dynamic range. It also reduces the transmission data rate of the recording chip. Both of these features allow power and area savings at the system level. Other advantages of the proposed topology are increased reliability due to the removal of pseudo-resistors, lower harmonic distortion and low-voltage operation. An analysis of the reconstruction error introduced by this scheme is presented along with a behavioral model to provide a quick estimate of the post reconstruction dynamic range. Measurement results from two different core amplifier designs in 65 nm and 180 nm CMOS processes are presented to prove the generality of the proposed scheme in the neural recording applications. Operating from a 1 V power supply, the amplifier in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise of 3.8 μVrms and power dissipation of 2.52 μW leading to a NEF of 3.1 in spike band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band. It also reduces system level power (by reducing the number of bits in the ADC by 2) as well as data rate to 80% of a conventional design. In vivo measurements validate the ability of this amplifier to simultaneously record spike and LFP signals.

  7. Development of high power CW and pulsed RF test facility based on 1 MW, 352.2 MHz klystron amplifier

    International Nuclear Information System (INIS)

    Badapanda, M.K.; Tripathi, Akhilesh; Upadhyay, Rinki; Rao, J.N.; Tiwari, Ashish; Jain, Akhilesh; Lad, M.R.; Hannurkar, P.R.

    2013-01-01

    A high power 1 MW, 352.2 MHz RF Test facility having CW and Pulse capability is being developed at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore for performance evaluation of various RF components, accelerating structures and related subsystems. Thales make 1 MW, 352.2 MHz klystron amplifier (TH 2089) will be employed in this high power test facility, which is thoroughly tested for its performance parameters at rated operating conditions. Auxiliary power supplies like filament, electromagnet, ion pump and mod anode power supply as well as 200 W solid state driver amplifier necessary for this high power test facility have been developed. A high voltage floating platform is created for floating filament and mod anode power supplies. Interconnection of various power supplies and other subsystems of this test facility are being carried out. A high voltage 100 kV, 25 Amp DC crowbar less power supply and low conductivity water (LCW) plant required for this klystron amplifier are in advanced stage of development. NI make cRIO 9081 real time (RT) controller based control and interlock system has been developed to realize proper sequence of operation of various power supplies and to monitor the status of crucial parameters in this test facility. This RF test facility will provide confidence for development of RF System of future accelerators like SNS and ADSS. (author)

  8. A second-order class-D audio amplifier

    OpenAIRE

    Cox, Stephen M.; Tan, M.T.; Yu, J.

    2011-01-01

    Class-D audio amplifiers are particularly efficient, and this efficiency has led to their ubiquity in a wide range of modern electronic appliances. Their output takes the form of a high-frequency square wave whose duty cycle (ratio of on-time to off-time) is modulated at low frequency according to the audio signal. A mathematical model is developed here for a second-order class-D amplifier design (i.e., containing one second-order integrator) with negative feedback. We derive exact expression...

  9. Population structure of Salmonella investigated by amplified fragment length polymorphism

    DEFF Research Database (Denmark)

    Torpdahl, M.; Ahrens, Peter

    2004-01-01

    Aims: This study was undertaken to investigate the usefulness of amplified fragment length polymorphism (AFLP) in determining the population structure of Salmonella. Methods and Results: A total of 89 strains were subjected to AFLP analysis using the enzymes BglII and BspDI, a combination...... that is novel in Salmonella. Both species S. bongori and S. enterica and all subsp. of S. enterica were represented with emphasis on S. enterica subsp. enterica using a local strain collection and strains from the Salmonella Reference Collection B (SARB). The amplified fragments were used in a band...

  10. Tapered amplifier laser with frequency-shifted feedback

    Directory of Open Access Journals (Sweden)

    A. Bayerle, S. Tzanova, P. Vlaar, B. Pasquiou, F. Schreck

    2016-10-01

    Full Text Available We present a frequency-shifted feedback (FSF laser based on a tapered amplifier. The laser operates as a coherent broadband source with up to 370GHz spectral width and 2.3us coherence time. If the FSF laser is seeded by a continuous-wave laser a frequency comb spanning the output spectrum appears in addition to the broadband emission. The laser has an output power of 280mW and a center wavelength of 780nm. The ease and flexibility of use of tapered amplifiers makes our FSF laser attractive for a wide range of applications, especially in metrology.

  11. Current-Driven Switch-Mode Audio Power Amplifiers

    DEFF Research Database (Denmark)

    Knott, Arnold; Buhl, Niels Christian; Andersen, Michael A. E.

    2012-01-01

    The conversion of electrical energy into sound waves by electromechanical transducers is proportional to the current through the coil of the transducer. However virtually all audio power amplifiers provide a controlled voltage through the interface to the transducer. This paper is presenting...... a switch-mode audio power amplifier not only providing controlled current but also being supplied by current. This results in an output filter size reduction by a factor of 6. The implemented prototype shows decent audio performance with THD + N below 0.1 %....

  12. A Method To ModifyCorrect The Performance Of Amplifiers

    Directory of Open Access Journals (Sweden)

    Rohith Krishnan R

    2015-01-01

    Full Text Available Abstract The actual response of the amplifier may vary with the replacement of some aged or damaged components and this method is to compensate that problem. Here we use op-amp Fixator as the design tool. The tool helps us to isolate the selected circuit component from rest of the circuit adjust its operating point to correct the performance deviations and to modify the circuit without changing other parts of the circuit. A method to modifycorrect the performance of amplifiers by properly redesign the circuit is presented in this paper.

  13. Dispersion-Engineered Traveling Wave Kinetic Inductance Parametric Amplifier

    Science.gov (United States)

    Zmuidzinas, Jonas (Inventor); Day, Peter K. (Inventor)

    2014-01-01

    A traveling wave kinetic inductance parametric amplifier comprises a superconducting transmission line and a dispersion control element. The transmission line can include periodic variations of its dimension along its length. The superconducting material can include a high normal state resistivity material. In some instances the high normal state resistivity material includes nitrogen and a metal selected from the group consisting of titanium, niobium and vanadium. The traveling wave kinetic inductance parametric amplifier is expected to exhibit a noise temperature below 100 mK/GHz.

  14. A European Project on Vacuum Tube Amplifiers for THz Amplification

    DEFF Research Database (Denmark)

    Paoloni, Claudio; Di Carlo, Aldo; Brunetti, Francesca

    2012-01-01

    The OPTHER (Optically Driven THz amplifier) project supported by the European Commission within the Seventh Framework Program (FP7) represents the first joint European attempt to realize vacuum electron devices in THz range. The target of the project was to design and realize the first 1 THz vacuum...... tube amplifier. The challenges of the presented task and the innovative solutions adopted established a new level of knowledge in the field. The main aspects of the OPTHER project are described, focusing on challenges and adopted innovative solutions....

  15. Gain dynamics and saturation in semiconductor quantum dot amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper; Hvam, Jørn Märcher

    2004-01-01

    Quantum dot (QD)-based semiconductor optical amplifiers offer unique properties compared with conventional devices based on bulk or quantum well material. Due to the bandfilling properties of QDs and the existence of a nearby reservoir of carriers in the form of a wetting layer, QD semiconductor...... optical amplifiers may be operated in regimes of high linearity, i.e. with a high saturation power, but can also show strong and fast nonlinearities by breaking the equilibrium between discrete dot states and the continuum of wetting layer states. In this paper, we analyse the interplay of these two...

  16. Thermal-recovery of modal instability in rod fiber amplifiers

    DEFF Research Database (Denmark)

    Jørgensen, Mette Marie; Laurila, Marko; Noordegraaf, Danny

    2013-01-01

    We investigate the temporal dynamics of Modal instabilities (MI) in ROD fiber amplifiers using a 100 μm core rod fiber in a single-pass amplifier configuration, and we achieve ~200W of extracted output power before the onset of MI. Above the MI threshold, we investigate the temporal dynamics of b...... and thermally annealed between each test series. We find that the MI threshold degrades as it is reached multiple times, but is recovered by thermal annealing. We also find that the test history of the rods affects the temporal dynamics....

  17. Nonclassical photon streams using rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    Ledingham, Patrick M.; Naylor, William R.; Longdell, Jevon J.; Beavan, Sarah E.; Sellars, Matthew J.

    2010-01-01

    We present a fully quantum mechanical treatment of optically rephased photon echoes. These echoes exhibit noise due to amplified spontaneous emission; however, this noise can be seen as a consequence of the entanglement between the atoms and the output light. With a rephasing pulse one can get an 'echo' of the amplified spontaneous emission, leading to light with nonclassical correlations at points separated in time, which is of interest in the context of building wide bandwith quantum repeaters. We also suggest a wideband version of DLCZ protocol based on the same ideas.

  18. 1000 kW ICRH amplifiers for MFTF-B

    International Nuclear Information System (INIS)

    Boksberger, U.

    1986-01-01

    For the startup of the MFTF-B ICRH heating will be applied. Two commercial amplifiers derived from standard broadcast transmitters provide 1000 kW RF power each into a matching system for any VSWR as high as 1.5. Emphasis is put on the specific environment of magnetic fields and seismic loads as well as to the particular RF power control requirements and remote operation. Also addressed is the amplifier's performance into a typical load. The load variations due to the MFTF-B plasma coupling were calculated by TRW

  19. Optimal Operation of a Josephson Parametric Amplifier for Vacuum Squeezing

    Science.gov (United States)

    Malnou, M.; Palken, D. A.; Vale, Leila R.; Hilton, Gene C.; Lehnert, K. W.

    2018-04-01

    A Josephson parametric amplifier (JPA) can create squeezed states of microwave light, lowering the noise associated with certain quantum measurements. We experimentally study how the JPA's pump influences the phase-sensitive amplification and deamplification of a coherent tone's amplitude when that amplitude is commensurate with vacuum fluctuations. We predict and demonstrate that, by operating the JPA with a single current pump whose power is greater than the value that maximizes gain, the amplifier distortion is reduced and, consequently, squeezing is improved. Optimizing the singly pumped JPA's operation in this fashion, we directly observe 3.87 ±0.03 dB of vacuum squeezing over a bandwidth of 30 MHz.

  20. Efficient trigger signal generation from wasted backward amplified stimulated emission at optical amplifiers for optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Kim Seung Taek

    2015-01-01

    Full Text Available This paper propose an optical structure to generate trigger signals for optical coherence tomography (OCT using backward light which is usually disposed. The backward light is called backward amplified stimulated emission generated from semiconductor optical amplifier (SOA when using swept wavelength tunable laser (SWTL. A circulator is applied to block undesirable lights in the SWTL instead of an isolator in common SWTL. The circulator also diverts backward amplified spontaneous lights, which finally bring out trigger signals for a high speed digitizer. The spectra of the forward lights at SOA and the waveform of the backward lights were measured to check the procedure of the trigger formation in the experiment. The results showed that the trigger signals from the proposed SWTL with the circulator was quite usable in OCT.

  1. Design of a high-gain laser diode-array pumped Nd:YAG alternating precessive slab amplifier (APS amplifier)

    Science.gov (United States)

    Coyle, D. B.

    1991-01-01

    In the design of space-qualifiable laser systems for ranging and altimetry, such as NASA's Geodynamic Laser Ranging System (GLRS), the transmitter must be kept small, powerful yet efficient, and must consist of as few components as possible. A novel preamplifier design is examined which requires no external beam steering optics, yielding a compact component with simple alignment procedures. The gains achieved are comparable to multipass zigzag amplifiers using two or more sets of external optics for extra passes through the amplifying medium.

  2. 2R Regeneration in Concatenated Semiconductor Optical Amplifiers and Electroabsorbers

    DEFF Research Database (Denmark)

    Christiansen, Lotte Jin; Xu, Lin; Yvind, Kresten

    2004-01-01

    We present a novel 2R regenerator with a large level separation and steep step a sharp, adjustable threshold based on concatenated semiconductor optical amplifiers and electroabsorbers. We demonstrate demonstrate improvements in both extinction-ratio and BER sensitivity atfor a 10 Gb/s NRZ signal....

  3. Giant Geometrically Amplified Piezoresistance in Metal-Semiconductor Hybrid Resistors

    DEFF Research Database (Denmark)

    Hansen, Ole; Reck, Kasper; Thomsen, Erik Vilain

    2008-01-01

    We show that very high geometrically amplified piezoresistance can indeed be obtained in microstructured metal-semiconductor hybrid devices, even significantly higher amplification factors than the factor of approximately 8 demonstrated recently by Rowe and co-workers may be achieved. However, we...... than the sensitivity of conventional piezoresistors fabricated in the same piezoresistive material. ©2008 American Institute of Physics...

  4. Trial manufacture of inside ellipse mirror for laser amplifier

    International Nuclear Information System (INIS)

    Kodama, Kenzo; Numajiri, Fumio; Kikuta, Yozo; Takasawa, Minoru; Oohira, Susumu; Nagaoka, Isao

    1984-01-01

    Inside ellipse mirrors have been trially manufactured for high power glass laser amplifiers. Their cutting process, machining, surface roughness, usage of cutting tools, materials, and processing process are given. Trial manufacture of supplementary devices for adjusting the direction of laser beam axis is also given. (author)

  5. Development and energization of IOT based RF amplifier

    International Nuclear Information System (INIS)

    Mandal, A.; Som, S.; Raj, P.R.; Manna, S.K.; Ghosh, S.; Seth, S.; Thakurta, S.; Thakur, S.K.; Saha, S.; Panda, U.S.

    2013-01-01

    A 704 MHz IOT based CW RF amplifier has been developed in VECC. It can also be used with proper tuning to power cavity modules operating at 650 MHz in high energy high intensity proton linear accelerator proposed to be built for ADSS/SNS programme in India and Project-X at Fermilab, USA. This IOT based amplifier provides up to 60 kW continuous wave RF power at 700 MHz. It required various power supplies, LCW cooling and forced air cooling for its operation. The auxiliary power supplies like Grid, Filament and Ion-pump, are floated and mounted on an isolated frame, i.e., HV deck. The mains inputs are electrically isolated by means of isolation transformer. Also, a Programmable Logic Controller (PLC) based interlocks along with high voltage collector power supply has been designed and developed for the safe operation of the RF amplifier. This paper discusses about various developments and energization of the IOT based RF amplifier with high power dummy load. (author)

  6. Short pulse mid-infrared amplifier for high average power

    CSIR Research Space (South Africa)

    Botha, LR

    2006-09-01

    Full Text Available High pressure CO2 lasers are good candidates for amplifying picosecond mid infrared pulses. High pressure CO2 lasers are notorious for being unreliable and difficult to operate. In this paper a high pressure CO2 laser is presented based on well...

  7. Application of amplified fragment length polymorphism (AFLPs) for ...

    African Journals Online (AJOL)

    Uapaca kirkiana Muell. Årg is a dioecious fruit tree species for priority domestication in Southern Africa. It reaches reproductive maturity in eight to ten years with male plants making up 50% of breeding populations. Early identification of sex of seedlings is a prerequisite for selection and tree improvement. The amplified ...

  8. Frequency resolved transverse mode instability in rod fiber amplifiers

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Laurila, Marko; Maack, Martin D.

    2013-01-01

    Frequency dynamics of transverse mode instabilities (TMIs) are investigated by testing three 285/100 rod fibers in a single-pass amplifier setup reaching up to ~200W of extracted output power without beam instabilities. The pump power is increased well above the TMI threshold to uncover output dy...

  9. Temporal and transverse coherence of self-amplified spontaneous emission

    International Nuclear Information System (INIS)

    Kim, K.J.

    1997-06-01

    The authors review the coherence properties of the self-amplified spontaneous emission (SASE). Temporally, SASE is similar to the spontaneous undulator radiation except that the spectral bandwidth is about ten times narrower compared with typical undulator radiation. The situation is quite different in the transverse dimension, where SASE is fully coherent

  10. Using a sequence characterized amplified region (SCAR) marker for ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-13

    Sep 13, 2010 ... This work used sequence characterized amplified region (SCAR) marker to detect the Bacillus cereus strain in strawberry fields. The purpose was to develop an effective molecular method for detecting the functional target microorganisms applied in agricultural fields. A 3×109. CFU/ml vegetative cell.

  11. Design of wideband hybrid amplifiers for local area networks

    Czech Academy of Sciences Publication Activity Database

    Karásek, Miroslav; Menif, M.; Bellemare, A.

    2001-01-01

    Roč. 148, č. 3 (2001), s. 150-155 ISSN 1350-2433 Grant - others:EU COST(XE) OC 265.10 Institutional research plan: CEZ:AV0Z2067918 Keywords : optical fibre amplifiers * wavelength division multiplexing * Raman spectra Subject RIV: BH - Optics, Masers, Lasers Impact factor: 0.611, year: 2001

  12. Development of a sequence characterized amplified region (SCAR ...

    African Journals Online (AJOL)

    The varieties of rice are difficult to be distinguished because of their similar morphological characters, therefore rice variety identification or differentiation is very important. The authentication by using molecular marker or DNA fingerprinting is the most accurate method. In this study, random amplified polymorphic DNA ...

  13. Entanglement-based linear-optical qubit amplifier

    Czech Academy of Sciences Publication Activity Database

    Meyer-Scott, E.; Bula, M.; Bartkiewicz, K.; Černoch, Antonín; Soubusta, Jan; Jennewein, T.; Lemr, Karel

    2013-01-01

    Roč. 87, č. 1 (2013), "012327-1"-"012327-7" ISSN 1050-2947 R&D Projects: GA ČR GAP205/12/0382 Institutional support: RVO:68378271 Keywords : quantum physics * photonics qubits * qubit amplifier Subject RIV: BH - Optics, Masers, Lasers Impact factor: 2.991, year: 2013

  14. Detection of somaclonal variation by random amplified polymorphic ...

    African Journals Online (AJOL)

    Detection of somaclonal variation by random amplified polymorphic DNA analysis during micropropagation of Phalaenopsis bellina (Rchb.f.) Christenson. ... Among the primers used, P 16 produced the highest number of bands (29), while primer OPU 10 produced the lowest number (15). The range of similarity coefficient ...

  15. Inter simple sequence repeats (ISSR) and random amplified ...

    African Journals Online (AJOL)

    21 of 30 random amplified polymorphic DNA (RAPD) primers produced 220 reproducible bands with average of 10.47 bands per primer and 80.12% of polymorphism. OPR02 primer showed the highest number of effective allele (Ne), Shannon index (I) and genetic diversity (H). Some of the cultivars had specific bands, ...

  16. Detailed design analysis of erbium-doped fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, Bo; Bjarklev, Anders Overgaard; Lumholt, Ole

    1991-01-01

    When pumping the erbium-doped fiber amplifier at 0.98 and 1.48 mu m, the optimum cutoff wavelength for step profiles with arbitrary numerical aperture is shown to be 0.80 and 0.90 mu m, respectively. The use of a confined erbium profile can improve the gain coefficient up to 45%. The index raising...

  17. Accurate simulation of Raman amplified lightwave synthesized frequency sweeper

    DEFF Research Database (Denmark)

    Pedersen, Anders Tegtmeier; Olesen, Anders Sig; Rottwitt, Karsten

    2011-01-01

    A lightwave synthesized frequency sweeper using a Raman amplifier for loss compensation is presented together with a numerical model capable of predicting the shape of individual pulses as well as the overall envelope of more than 100 pulses. The generated pulse envelope consists of 116 pulses wi...

  18. Application of random amplified polymorphic DNA (RAPD) markers ...

    African Journals Online (AJOL)

    The random amplified polymorphic DNA (RAPD) technique has been widely applied to identify different varieties of plants for molecular breeding. However, application of RAPD markers to identify parthenogenesis in plants has not been reported. In this investigation, we used pedigree and RAPD markers to differentiate ...

  19. Self-pulsation threshold of Raman amplified Brillouin fiber cavities

    DEFF Research Database (Denmark)

    Ott, Johan Raunkjær; Pedersen, Martin Erland Vestergaard; Rottwitt, Karsten

    2009-01-01

    An implicit equation for the oscillation threshold of stimulated Brillouin scattering from Raman amplified signals in fibers with external feedback is derived under the assumption of no depletion. This is compared to numerical investigations of Raman amplification schemes showing good agreement...

  20. Random amplified polymorphic DNA (RAPD) markers reveal genetic ...

    African Journals Online (AJOL)

    The present study evaluated genetic variability of superior bael genotypes collected from different parts of Andaman Islands, India using fruit characters and random amplified polymorphic DNA (RAPD) markers. Genomic DNA extracted from leaf material using cetyl trimethyl ammonium bromide (CTAB) method was ...