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Sample records for chemoresistance acquisition induces

  1. Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells

    NARCIS (Netherlands)

    Michaelis, Martin; Klassert, Denise; Barth, Susanne; Suhan, Tatyana; Breitling, Rainer; Mayer, Bernd; Hinsch, Nora; Doerr, Hans W.; Cinatl, Jaroslav; Cinatl, Jindrich; Cinatl jr., Jindrich

    2009-01-01

    Background: Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. Results: Bioinformatics analysis of gene expression data revealed that expression of

  2. Oncologic trogocytosis of an original stromal cells induces chemoresistance of ovarian tumours.

    Directory of Open Access Journals (Sweden)

    Arash Rafii

    Full Text Available The microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.We isolated an original type of stromal cells, referred to as "Hospicells" from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.This is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient's tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.

  3. Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse.

    Science.gov (United States)

    Ogden, Angela; Rida, Padmashree C G; Knudsen, Beatrice S; Kucuk, Omer; Aneja, Ritu

    2015-10-28

    Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combatted by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

    International Nuclear Information System (INIS)

    Ricciardelli, Carmela; Ween, Miranda P; Lokman, Noor A; Tan, Izza A; Pyragius, Carmen E; Oehler, Martin K

    2013-01-01

    Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC

  5. CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.

    Science.gov (United States)

    Pasquier, Jennifer; Gosset, Marie; Geyl, Caroline; Hoarau-Véchot, Jessica; Chevrot, Audrey; Pocard, Marc; Mirshahi, Massoud; Lis, Raphael; Rafii, Arash; Touboul, Cyril

    2018-02-19

    Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation. We combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions. We demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation. These findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.

  6. Cyclophilin B induces chemoresistance by degrading wild type p53 via interaction with MDM2 in colorectal cancer.

    Science.gov (United States)

    Choi, Tae Gyu; Nguyen, Minh Nam; Kim, Jieun; Jo, Yong Hwa; Jang, Miran; Nguyen, Ngoc Ngo Yen; Yun, Hyeong Rok; Choe, Wonchae; Kang, Insug; Ha, Joohun; Tang, Dean G; Kim, Sung Soo

    2018-06-06

    Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Chemoresistance is a major problem for effective therapy in CRC. Here, we investigated the mechanism by which peptidylprolyl isomerase B (PPIB; cyclophilin B, CypB) regulates chemoresistance in CRC. We found that CypB is a novel wild type p53 (p53WT)-inducible gene but a negative regulator of p53WT in response to oxaliplatin treatment. Overexpression of CypB shortens the half-life of p53WT and inhibits oxaliplatin-induced apoptosis in CRC cells, whereas knockdown of CypB lengthens the half-life of p53WT and stimulates p53WT dependent apoptosis. CypB interacts directly with MDM2, and enhances MDM2-dependent p53WT ubiquitination and degradation. Furthermore, we firmly validated using bioinformatics analyses that overexpression of CypB is associated with poor prognosis in CRC progression and chemoresistance. Hence, we suggest a novel mechanism of chemoresistance caused by overexpressed CypB, which may help to develop new anti-cancer drugs. We also propose that CypB may be utilized as a predictive biomarker in CRC patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

    Science.gov (United States)

    Bilyeu, Jennifer D; Panta, Ganesh R; Cavin, Lakita G; Barrett, Christina M; Turner, Eddie J; Sweatman, Trevor W; Israel, Mervyn; Lothstein, Leonard; Arsura, Marcello

    2004-04-01

    Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines. We show that the induction of NF-kappaB activity in response to drug treatment relies on the activation of PKC-delta and NF-kappaB-activating kinase (NAK), independent of ataxia telengectasia mutated and p53 activities. In turn, NAK activates the IKK complex through phosphorylation of the IKK-2 subunit. We find that neither NF-kappaB activation nor ectopic expression of Bcl-X(L) confers protection from AD 198-induced cell killing. Overall, our data indicate that activation of novel PKC isoforms by cytoplasmic-targeted 14-O-acylanthracyclines promotes an apoptotic response independent of DNA damage, which is unimpeded by inducible activation of NF-kappaB.

  8. Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline.

    Science.gov (United States)

    Wang, Tung Yuan; Peng, Chih-Yu; Lee, Shiuan-Shinn; Chou, Ming-Yung; Yu, Cheng-Chia; Chang, Yu-Chao

    2016-12-20

    Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3' UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.

  9. UPregulated single-stranded DNA-binding protein 1 induces cell chemoresistance to cisplatin in lung cancer cell lines.

    Science.gov (United States)

    Zhao, Xiang; He, Rong; Liu, Yu; Wu, Yongkai; Kang, Leitao

    2017-07-01

    Cisplatin and its analogues are widely used as anti-tumor drugs in lung cancer but many cisplatin-resistant lung cancer cases have been identified in recent years. Single-stranded DNA-binding protein 1 (SSDBP1) can effectively induce H69 cell resistance to cisplatin in our previous identification; thus, it is necessary to explore the mechanism underlying the effects of SSDBP1-induced resistance to cisplatin. First, SSDBP1-overexpressed or silent cell line was constructed and used to analyze the effects of SSDBP1 on chemoresistance of lung cancer cells to cisplatin. SSDBP1 expression was assayed by real-time PCR and Western blot. Next, the effects of SSDBP1 on cisplatin sensitivity, proliferation, and apoptosis of lung cancer cell lines were assayed by MTT and flow cytometry, respectively; ABC transporters, apoptosis-related genes, and cell cycle-related genes by real-time PCR, and DNA wound repair by comet assay. Low expression of SSDBP1 was observed in H69 cells, while increased expression in cisplatin-resistant H69 cells. Upregulated expression of SSDBP1 in H69AR cells was identified to promote proliferation and cisplatin resistance and inhibit apoptosis, while downregulation of SSDBP1 to inhibit cisplatin resistance and proliferation and promoted apoptosis. Moreover, SSDBP1 promoted the expression of P2gp, MRP1, Cyclin D1, and CDK4 and inhibited the expression of caspase 3 and caspase 9. Furthermore, SSDBP1 promoted the DNA wound repair. These results indicated that SSDBP1 may induce cell chemoresistance of cisplatin through promoting DNA repair, resistance-related gene expression, cell proliferation, and inhibiting apoptosis.

  10. Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

    Directory of Open Access Journals (Sweden)

    Zou Jie

    2013-01-01

    Full Text Available Abstract Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL. Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1 transfected with HIF-1α or Notch1 small interference RNA (siRNA were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2 and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation

  11. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

    Science.gov (United States)

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

    2016-10-15

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wei Z

    2018-03-01

    . Conclusion: Taken together, our results show that GPt demonstrates superiority in combating hypoxia-induced chemoresistance. It might serve as a novel strategy for future microenvironment-targeted cancer therapy. Keywords: hypoxia tumor microenvironment, graphene oxide quantum dots, chemoresistance, Pt-loaded nanocomplexes, oral squamous cell carcinoma

  13. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    Science.gov (United States)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-08-06

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

  14. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    International Nuclear Information System (INIS)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

  15. TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver cancer cells

    International Nuclear Information System (INIS)

    Flamant, Lionel; Roegiers, Edith; Pierre, Michael; Hayez, Aurélie; Sterpin, Christiane; De Backer, Olivier; Arnould, Thierry; Poumay, Yves; Michiels, Carine

    2012-01-01

    Hypoxia is a common characteristic of solid tumors associated with reduced response to radio- and chemotherapy, therefore increasing the probability of tumor recurrence. The aim of this study was to identify new mechanisms responsible for hypoxia-induced resistance in breast cancer cells. MDA-MB-231 and HepG2 cells were incubated in the presence of taxol or etoposide respectively under normoxia and hypoxia and apoptosis was analysed. A whole transcriptome analysis was performed in order to identify genes whose expression profile was correlated with apoptosis. The effect of gene invalidation using siRNA was studied on drug-induced apoptosis. MDA-MB-231 cells incubated in the presence of taxol were protected from apoptosis and cell death by hypoxia. We demonstrated that TMEM45A expression was associated with taxol resistance. TMEM45A expression was increased both in MDA-MB-231 human breast cancer cells and in HepG2 human hepatoma cells in conditions where protection of cells against apoptosis induced by chemotherapeutic agents was observed, i.e. under hypoxia in the presence of taxol or etoposide. Moreover, this resistance was suppressed by siRNA-mediated silencing of TMEM45A. Kaplan Meier curve showed an association between high TMEM45A expression and poor prognostic in breast cancer patients. Finally, TMEM45 is highly expressed in normal differentiated keratinocytes both in vitro and in vivo, suggesting that this protein is involved in epithelial functions. Altogether, our results unravel a new mechanism for taxol and etoposide resistance mediated by TMEM45A. High levels of TMEM45A expression in tumors may be indicative of potential resistance to cancer therapy, making TMEM45A an interesting biomarker for resistance

  16. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells

    OpenAIRE

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro

    2016-01-01

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance lo...

  17. 3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing

    International Nuclear Information System (INIS)

    Longati, Paola; Heuchel, Rainer L; Jia, Xiaohui; Eimer, Johannes; Wagman, Annika; Witt, Michael-Robin; Rehnmark, Stefan; Verbeke, Caroline; Toftgård, Rune; Löhr, Matthias

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance

  18. Chemoresistive gas sensor

    Science.gov (United States)

    Hirschfeld, T.B.

    1987-06-23

    A chemoresistive gas sensor is provided which has improved sensitivity. A layer of organic semiconductor is disposed between two electrodes which, in turn, are connected to a voltage source. High conductivity material is dispersed within the layer of organic semiconductor in the form of very small particles, or islands. The average interisland spacing is selected so that the predominant mode of current flow is by way of electron funneling. Adsorption of gaseous contaminant onto the layer of organic semiconductor modulates the tunneling current in a quantitative manner. 2 figs.

  19. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance

    International Nuclear Information System (INIS)

    Singh, Mohan; Chaudhry, Parvesh; Fabi, Francois; Asselin, Eric

    2013-01-01

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells

  20. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Fabi, Francois; Asselin, Eric

    2013-05-10

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells.

  1. Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

    LENUS (Irish Health Repository)

    McEvoy, Lynda M

    2015-01-01

    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.

  2. Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Massimiliano Cadamuro

    2017-01-01

    Full Text Available Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.

  3. First Fifty Years of Chemoresistive Gas Sensors

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    Giovanni Neri

    2015-01-01

    Full Text Available The first fifty years of chemoresistive sensors for gas detection are here reviewed, focusing on the main scientific and technological innovations that have occurred in the field over the course of these years. A look at advances made in fundamental and applied research and leading to the development of actual high performance chemoresistive devices is presented. The approaches devoted to the synthesis of novel semiconducting materials with unprecedented nanostructure and gas-sensing properties have been also presented. Perspectives on new technologies and future applications of chemoresistive gas sensors have also been highlighted.

  4. Ultrasound sensitizes chemotherapy in chemoresistant ovarian ...

    African Journals Online (AJOL)

    Administrator

    2011-09-26

    Sep 26, 2011 ... The addition of noncytotoxic insonation led to a higher cell-death ... Overcoming chemoresistance can efficiently deactivate cancer cells, ..... In: Nowak. FM (eds) Sonochemistry: Theory, Reactions, Syntheses, and. Applications ...

  5. Mechanisms of chemoresistance to alkylating agents in malignant glioma.

    Science.gov (United States)

    Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

    2008-05-15

    Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

  6. Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response.

    Science.gov (United States)

    Hombach-Klonisch, Sabine; Mehrpour, Maryam; Shojaei, Shahla; Harlos, Craig; Pitz, Marshall; Hamai, Ahmed; Siemianowicz, Krzysztof; Likus, Wirginia; Wiechec, Emilia; Toyota, Brian D; Hoshyar, Reyhane; Seyfoori, Amir; Sepehri, Zahra; Ande, Sudharsana R; Khadem, Forough; Akbari, Mohsen; Gorman, Adrienne M; Samali, Afshin; Klonisch, Thomas; Ghavami, Saeid

    2018-04-01

    Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype.

    Science.gov (United States)

    Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-11-24

    DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance.

  8. Design of remote laser-induced fluorescence system's acquisition circuit

    Science.gov (United States)

    Wang, Guoqing; Lou, Yue; Wang, Ran; Yan, Debao; Li, Xin; Zhao, Xin; Chen, Dong; Zhao, Qi

    2017-10-01

    Laser-induced fluorescence system(LIfS) has been found its significant application in identifying one kind of substance from another by its properties even it's thimbleful, and becomes useful in plenty of fields. Many superior works have reported LIfS' theoretical analysis , designs and uses. However, the usual LIPS is always constructed in labs to detect matter quite closely, for the system using low-power laser as excitation source and charge coupled device (CCD) as detector. Promoting the detectivity of LIfS is of much concern to spread its application. Here, we take a high-energy narrow-pulse laser instead of commonly used continuous wave laser to operate sample, thus we can get strong fluorescent. Besides, photomultiplier (PMT) with high sensitivity is adopted in our system to detect extremely weak fluorescence after a long flight time from the sample to the detector. Another advantage in our system, as the fluorescence collected into spectroscopy, multiple wavelengths of light can be converted to the corresponding electrical signals with the linear array multichannel PMT. Therefore, at the cost of high-powered incentive and high-sensitive detector, a remote LIFS is get. In order to run this system, it is of importance to turn light signal to digital signal which can be processed by computer. The pulse width of fluorescence is deeply associated with excitation laser, at the nanosecond(ns) level, which has a high demand for acquisition circuit. We design an acquisition circuit including, I/V conversion circuit, amplifying circuit and peak-holding circuit. The simulation of circuit shows that peak-holding circuit can be one effective approach to reducing difficulty of acquisition circuit.

  9. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    International Nuclear Information System (INIS)

    Meier, Julia C; Haendler, Bernard; Seidel, Henrik; Groth, Philip; Adams, Robert; Ziegelbauer, Karl; Kreft, Bertolt; Beckmann, Georg; Sommer, Anette; Kopitz, Charlotte

    2015-01-01

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer

  10. Chemoresistance of CD133{sup +} colon cancer may be related with increased survivin expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Genomic Cohort, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133{sup +} colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133{sup −} cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133{sup +} and siRNA-induced CD133{sup −} cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133{sup +} cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133{sup +} cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133{sup +} cells at 96 h after siRNA transfection. From this study, we conclude that CD133{sup +} cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133{sup +} colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133{sup +} cells and siRNA-induced CD133{sup −} cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133{sup +} colon cancer cells.

  11. A Histone Deacetylase Inhibitor Suppresses Epithelial-Mesenchymal Transition and Attenuates Chemoresistance in Biliary Tract Cancer.

    Directory of Open Access Journals (Sweden)

    Takuya Sakamoto

    Full Text Available Epithelial-mesenchymal transition (EMT is involved in the characteristics of malignancy, such as invasion, metastasis, and chemoresistance. In biliary tract cancer (BTC, EMT is induced by transforming growth factor-beta 1 (TGF-β1. The EMT is reversible; therefore, it is conceivable that it could be related to some epigenetic changes. We focused on histone deacetylase (HDAC inhibitors as regulators of TGF-β1 signaling, and investigated their effect on EMT and chemoresistance. We employed four BTC cell lines (MzChA-1, gemcitabine-resistant MzChA-1, TFK-1, and gemcitabine-resistant TFK-1 and used vorinostat as the HDAC inhibitor. The relative mRNA expression of an epithelial marker (CDH1 and mesenchymal markers (CDH2, vimentin, SNAI1 were measured by qRT-PCR to evaluate factors associated with EMT. MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was performed to evaluate the chemoresistance of each cell line. In addition, NOD/SCID mice were used to evaluate the effect of vorinostat in vivo. In the parent MzChA-1 and TFK-1 cell lines, TGF-β1 induced EMT and chemoresistance; while vorinostat inhibited the EMT and chemoresistance induced by TGF-β1. In gemcitabine-resistant cell lines that highly expressed TGF-β1, vorinostat inhibited EMT and attenuated chemoresistance. We showed that vorinostat inhibits nuclear translocation of SMAD4 which is a signaling factor of TGF-β1, and this is one of the mechanisms by which vorinostat regulates EMT. We also showed that vorinostat attenuates the binding affinity of SMAD4 to the CDH1-related transcription factors SNAI1, SNAI2, ZEB1, ZEB2, and TWIST. Furthermore, combination therapy with vorinostat and gemcitabine improved survival time in the mice xenografted with gemcitabine resistant MzChA-1 cells. In conclusion, vorinostat regulated TGF-β1-induced EMT and chemoresistance through inhibition of SMAD4 nuclear translocation.

  12. CLDN6 promotes chemoresistance through GSTP1 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Minlan Yang

    2017-11-01

    Full Text Available Abstract Background Claudin-6 (CLDN6, a member of CLDN family and a key component of tight junction, has been reported to function as a tumor suppressor in breast cancer. However, whether CLDN6 plays any role in breast cancer chemoresistance remains unclear. In this study, we investigated the role of CLDN6 in the acquisition of chemoresistance in breast cancer cells. Methods We manipulated the expression of CLDN6 in MCF-7 and MCF-7/MDR cells with lv-CLDN6 and CLDN6-shRNA and investigated whether CLDN6 manipulation lead to different susceptibilities to several chemotherapeutic agents in these cells. The cytotoxicity of adriamycin (ADM, 5-fluorouracil (5-FU, and cisplatin (DDP was tested by cck-8 assay. Cell death was determined by DAPI nuclear staining. The enzyme activity of glutanthione S-transferase-p1 (GSTP1 was detected by a GST activity kit. Then lv-GSTP1 and GSTP1-shRNA plasmids were constructed to investigate the potential of GSTP1 in regulating chemoresistance of breast cancer. The TP53-shRNA was adopted to explore the regulation mechanism of GSTP1. Finally, immunohistochemistry was used to explore the relationship between CLDN6 and GSTP1 expression in breast cancer tissues. Results Silencing CLDN6 increased the cytotoxicity of ADM, 5-FU, and DDP in MCF-7/MDR cells. Whereas overexpression of CLDN6 in MCF-7, the parental cell line of MCF-7/MDR expressing low level of CLDN6, increased the resistance to the above drugs. GSTP1 was upregulated in CLDN6-overexpressed MCF-7 cells. RNAi –mediated silencing of CLDN6 downregulated both GSTP1 expression and GST enzyme activity in MCF-7/MDR cells. Overexpresssion of GSTP1 in CLDN6 silenced MCF-7/MDR cells restored chemoresistance, whereas silencing GSTP1 reduced the chemoresistance due to ectopic overexpressed of CLDN6 in MCF-7 cells. These observations were also repeated in TNBC cells Hs578t. We further confirmed that CLDN6 interacted with p53 and promoted translocation of p53 from nucleus to

  13. Effects of subdiaphragmatic vagotomy on the acquisition of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Hunt, W.A.; Rabin, B.M.; Lee, J.

    1987-01-01

    The effect of subdiaphragmatic vagotomy on the acquisition of a radiation-induced taste aversion was examined to assess the importance of the vagus nerve in transmitting information on the peripheral toxicity of radiation to the brain. Vagotomy had no effect on taste aversion learning, consistent with reports using other toxins. The data support the involvement of a blood-borne factor in the acquisition of taste aversion induced by ionizing radiation

  14. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    Science.gov (United States)

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  15. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

    Science.gov (United States)

    Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar

    2012-05-01

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

  16. β-Elemene Reverses Chemoresistance of Breast Cancer Cells by Reducing Resistance Transmission via Exosomes

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    Jun Zhang

    2015-07-01

    Full Text Available Background: Currently, exosomes that act as mediators of intercellular communication are being researched extensively. Our previous studies confirmed that these exosomes contain microRNAs (miRNAs that could alter chemo-susceptibility, which is partly attributed to the successful intercellular transfer of multidrug resistance (MDR-specific miRNAs. We also confirmed that β-elemene could influence MDR-related miRNA expression and regulate the expression of the target genes PTEN and Pgp, which may lead to the reversal of the chemoresistant breast cancer (BCA cells. We are the first to report these findings, and we propose the following logical hypothesis: β-elemene can mediate MDR-related miRNA expression in cells, thereby affecting the exosome contents, reducing chemoresistance transmission via exosomes, and reversing the drug resistance of breast cancer cells. Methods: MTT-cytotoxic, miRNA microarray, real-time quantitative PCR, Dual Luciferase Activity Assay, and Western blot analysis were performed to investigate the impact of β-elemene on the expression of chemoresistance specific miRNA and PTEN as well as Pgp in chemoresistant BCA exosomes. Results: Drug resistance can be reversed by β-elemene related to exosomes. There were 104 differentially expressed miRNAs in the exosomes of two chemoresistant BCA cells: adriacin (Adr - resistant MCF-7 cells (MCF-7/Adr and docetaxel (Doc - resistant MCF-7 cells (MCF-7/Doc that underwent treatment. Of these, 31 miRNAs were correlated with the constant changes in the MDR. The expression of miR-34a and miR-452 can lead to changes in the characteristics of two chemoresistant BCA exosomes: MCF-7/Adr exosomes (A/exo and MCF-7/Doc exosomes (D/exo. The PTEN expression affected by β-elemene was significantly increased, and the Pgp expression affected by β-elemene was significantly decreased in both cells and exosomes. β-elemene induced a significant increase in the apoptosis rate in both MCF-7/Doc and MCF-7

  17. Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.

    Science.gov (United States)

    Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

    2015-07-31

    CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma

    Science.gov (United States)

    Qin, Z; Dai, L; Bratoeva, M; Slomiany, MG; Toole, BP; Parsons, C

    2013-01-01

    The Kaposi’s sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), for which cytotoxic chemotherapy represents the standard of care. The high mortality associated with PEL may be explained in part by resistance of these tumors to chemotherapy. The membrane-bound glycoprotein emmprin (CD147) enhances chemoresistance in tumors through effects on transporter expression, trafficking and interactions. Interactions between hyaluronan and hyaluronan receptors on the cell surface also facilitate emmprin-mediated chemoresistance. Whether emmprin or hyaluronan-receptor interactions regulate chemotherapeutic resistance for virus-associated malignancies is unknown. Using human PEL tumor cells, we found that PEL sensitivity to chemotherapy is directly proportional to expression of emmprin, the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and a drug transporter known as the breast cancer resistance protein/ABCG2 (BCRP), and that emmprin, LYVE-1 and BCRP interact with each other and colocalize on the PEL cell surface. In addition, we found that emmprin induces chemoresistance in PEL cells through upregulation of BCRP expression, and RNA interference targeting of emmprin, LYVE-1 or BCRP enhances PEL cell apoptosis induced by chemotherapy. Finally, disruption of hyaluronan-receptor interactions using small hyaluronan oligosaccharides reduces expression of emmprin and BCRP while sensitizing PEL cells to chemotherapy. Collectively, these data support interdependent roles for emmprin, LYVE-1 and BCRP in chemotherapeutic resistance for PEL. PMID:21660043

  19. Role of the pituitary-adrenal hormones in the acquisition of schedule-induced polydipsia.

    Science.gov (United States)

    Levine, R; Levine, S

    1989-06-01

    Adrenalectomized female rats failed to develop schedule-induced polydipsia (SIP). Dexamethasone (DEX) injections failed to reinstate SIP in adrenalectomized rats. They did not prevent intact rats from acquiring SIP but interfered with subsequent expression of this behavior. In contrast, corticosterone, the rats' normally occurring glucocorticoid, fully restored the acquisition and subsequent expression of SIP in adrenalectomized rats. This strongly suggests that corticosterone plays an essential role in the normal acquisition and development of this behavior. Data are interpreted in the context of current information concerning adrenal hormone receptors. It is hypothesized SIP acquisition is at least partly regulated by the Type I (mineralocorticoid) receptor.

  20. Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

    Science.gov (United States)

    van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

    2013-01-01

    Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

  1. TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells.

    Science.gov (United States)

    Bartucci, M; Dattilo, R; Moriconi, C; Pagliuca, A; Mottolese, M; Federici, G; Benedetto, A Di; Todaro, M; Stassi, G; Sperati, F; Amabile, M I; Pilozzi, E; Patrizii, M; Biffoni, M; Maugeri-Saccà, M; Piccolo, S; De Maria, R

    2015-02-05

    Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.

  2. Cytogenetic Evolution of Human Ovarian Cell Lines Associated with Chemoresistance and Loss of Tumorigenicity

    Directory of Open Access Journals (Sweden)

    Stéphanie Struski

    2003-01-01

    Full Text Available In order to identify genomic changes associated with a resistant phenotype acquisition, we used comparative genomic hybridization (CGH to compare a human ovarian cell line, Igrov1, and four derived subcell lines, resistant to vincristine and presenting a reversion of malignant properties. Multicolor FISH (Multiplex‐FISH and Spectral Karyotype and conventional FISH are also used to elucidate the karyotype of parental cell line. The drug‐resistant subcell lines displayed many chromosomal abnormalities suggesting the implication of different pathways leading to a multidrug resistance phenotype. However, these cell lines shared two common rearrangements: an unbalanced translocation der(8t(8;13(p22;q? and a deletion of the 11p. These chromosomal imbalances could reflected the acquisition of the chemoresistance (der(8 or the loss of tumorigenicity properties (del(11p. Colour figure can be viewed on http://www.esacp.org/acp/2003/25‐3/struski.htm.

  3. Evidence for the Task-Induced Involvement Construct in Incidental Vocabulary Acquisition through Digital Gaming

    Science.gov (United States)

    Reynolds, Barry Lee

    2017-01-01

    This article reports on an investigation of the suitability of mobile vocabulary games for inducing a state of incidental vocabulary acquisition. Draw Something, a social digital drawing game in which players draw and guess words, was selected as a focus for this investigation. Results from an exploratory factor analysis of the questionnaire data…

  4. SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David Hamisi Mvunta

    2017-08-01

    Full Text Available BACKGROUND: SIRT1 is a longevity gene that forestalls aging and age-related diseases including cancer, and has recently attracted widespread attention due to its overexpression in some cancers. We previously identified the overexpression of SIRT1 in ovarian carcinoma (OvCa as a poor prognostic factor. However, mechanistic insights into the function of SIRT1 in OvCa have yet to be elucidated. METHODS: Quantitative real-time reverse PCR (qRT-PCR and Western blotting were employed to examine the expression of SIRT1 in a panel of human OvCa cell lines. si-RNA or sh-RNA and cDNA technologies were utilized to knockdown or overexpress SIRT1, respectively. The effects of SIRT1 on proliferation and chemoresistance were examined using a WST-1 assay, and the underlying mechanisms were confirmed using an apoptotic assay, and the quantification of glutathione (GSH, and reactive oxygen species (ROS. The aggressiveness of SIRT1 was analyzed using in vitro invasion and migration assays. RESULTS: SIRT1 was more strongly expressed in OvCa cell lines than in the immortalized ovarian epithelium at the gene and protein levels. Stress up-regulated the expression of SIRT1 in dose- and time-dependent manners. SIRT1 significantly enhanced the proliferation (P < .05, chemoresistance (P < .05, and aggressiveness of OvCa cells by up-regulating multiple antioxidant pathways to inhibit oxidative stress. Further study into the overexpression of SIRT1 demonstrated the up-regulation of several stemness-associated genes and enrichment of CD44v9 via an as-yet-unidentified pathway. CONCLUSIONS: Our results suggest that SIRT1 plays a role in the acquisition of aggressiveness and chemoresistance by OvCa, and has potential as a therapeutic target for OvCa.

  5. Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1983-01-01

    The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself

  6. Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

    Science.gov (United States)

    Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

    2018-06-01

    Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT activation

    Science.gov (United States)

    Cioce, M; Canino, C; Goparaju, C; Yang, H; Carbone, M; Pass, H I

    2014-01-01

    Clinical management of malignant pleural mesothelioma (MPM) is very challenging because of the uncommon resistance of this tumor to chemotherapy. We report here increased expression of macrophage colony-stimulating-factor-1-receptor (M-CSF/CSF-1R) mRNA in mesothelioma versus normal tissue specimens and demonstrate that CSF-1R expression identifies chemoresistant cells of mesothelial nature in both primary cultures and mesothelioma cell lines. By using RNAi or ligand trapping, we demonstrate that the chemoresistance properties of those cells depend on autocrine CSF-1R signaling. At the single-cell level, the isolated CSF-1Rpos cells exhibit a complex repertoire of pluripotency, epithelial–mesenchymal transition and detoxifying factors, which define a clonogenic, chemoresistant, precursor-like cell sub-population. The simple activation of CSF-1R in untransformed mesothelial cells is sufficient to confer clonogenicity and resistance to pemetrexed, hallmarks of mesothelioma. In addition, this induced a gene expression profile highly mimicking that observed in the MPM cells endogenously expressing the receptor and the ligands, suggesting that CSF-1R expression is mainly responsible for the phenotype of the identified cell sub-populations. The survival of CSF1Rpos cells requires active AKT (v-akt murine thymoma viral oncogene homolog 1) signaling, which contributed to increased levels of nuclear, transcriptionally competent β-catenin. Inhibition of AKT reduced the transcriptional activity of β-catenin-dependent reporters and sensitized the cells to senescence-induced clonogenic death after pemetrexed treatment. This work expands what is known on the non-macrophage functions of CSF-1R and its role in solid tumors, and suggests that CSF-1R signaling may have a critical pathogenic role in a prototypical, inflammation-related cancer such as MPM and therefore may represent a promising target for therapeutic intervention. PMID:24722292

  8. Evidence of galectin-1 involvement in glioma chemoresistance

    International Nuclear Information System (INIS)

    Le Mercier, Marie; Lefranc, Florence; Mijatovic, Tatjana; Debeir, Olivier; Haibe-Kains, Benjamin; Bontempi, Gianluca; Decaestecker, Christine; Kiss, Robert; Mathieu, Veronique

    2008-01-01

    Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy; a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) whose expression is stimulated by hypoxia is a potent modulator of GBM cell migration and a pro-angiogenic molecule. Hypoxia is also known to confer cancer cells with resistance to chemotherapy and radiotherapy and to modulate the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. The present study investigates whether decreasing Gal1 expression (by means of a siRNA approach) in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs. The data reveal that temozolomide, the standard treatment for glioma patients, increases Gal1 expression in Hs683 cells both in vitro and in vivo. However, reducing Gal1 expression in these cells by siRNA increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide both in vitro and in vivo. This decrease in Gal1 expression in Hs683 cells does not induce apoptotic or autophagic features, but is found to modulate p53 transcriptional activity and decrease p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5 ATF3 and GADD45A. The decrease in Gal1 expression also impairs the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61, some of which are located in the ER and whose expression is also known to be modified by hypoxia. This novel facet of Gal1 involvement in glioblastoma biology may be amenable to therapeutic manipulation

  9. Acquisition of MDMA self-administration: pharmacokinetic factors and MDMA-induced serotonin release.

    Science.gov (United States)

    Bradbury, Sarah; Bird, Judith; Colussi-Mas, Joyce; Mueller, Melanie; Ricaurte, George; Schenk, Susan

    2014-09-01

    The current study aimed to elucidate the role of pharmacokinetic (PK) parameters and neurotransmitter efflux in explaining variability in (±) 3, 4-methylenedioxymethamphetamine (MDMA) self-administration in rats. PK profiles of MDMA and its major metabolites were determined after the administration of 1.0 mg/kg MDMA (iv) prior to, and following, the acquisition of MDMA self-administration. Synaptic levels of 5-hydroxytryptamine (5HT) and dopamine (DA) in the nucleus accumbens were measured following administration of MDMA (1.0 and 3.0 mg/kg, iv) using in vivo microdialysis and compared for rats that acquired or failed to acquire MDMA self-administration. Effects of the 5HT neurotoxin, 5,7 dihydroxytryptamine (5, 7-DHT), on the acquisition of MDMA and cocaine self-administration were also determined. In keeping with previous findings, approximately 50% of rats failed to meet a criterion for acquisition of MDMA self-administration. The PK profiles of MDMA and its metabolites did not differ between rats that acquired or failed to acquire MDMA self-administration. MDMA produced more overflow of 5HT than DA. The MDMA-induced 5HT overflow was lower in rats that acquired MDMA self-administration compared with those that did not acquire self-administration. In contrast, MDMA-induced DA overflow was comparable for the two groups. Prior 5,7-DHT lesions reduced tissue levels of 5HT and markedly increased the percentage of rats that acquired MDMA self-administration and also decreased the latency to acquisition of cocaine self-administration. These data suggest that 5HT limits the initial sensitivity to the positively reinforcing effects of MDMA and delays the acquisition of reliable self-administration. © 2013 Society for the Study of Addiction.

  10. Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells.

    Science.gov (United States)

    Wang, Xin; Low, Xinyi Casuarine; Hou, Weixin; Abdullah, Lissa Nurrul; Toh, Tan Boon; Mohd Abdul Rashid, Masturah; Ho, Dean; Chow, Edward Kai-Hua

    2014-12-23

    Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond-drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers.

  11. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

    2011-01-01

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  12. Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

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    Zhiqiang Meng

    Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

  13. Application of a digital data acquisition system for time of flight Positron annihilation-induced Auger Electron Spectroscopy

    Science.gov (United States)

    Gladen, R. W.; Chirayath, V. A.; McDonald, A. D.; Fairchild, A. J.; Chrysler, M. D.; Imam, S. K.; Koymen, A. R.; Weiss, A. H.

    We describe herein a digital data acquisition system for a time-of-flight Positron annihilation-induced Auger Electron Spectrometer. This data acquisition system consists of a high-speed digitizer collecting signals induced by Auger electrons and annihilation gammas in a multi-channel plate electron detector and a BaF2 gamma detector, respectively. The time intervals between these two signals is used to determine the times of flight of the Auger electrons, which are analyzed by algorithms based on traditional nuclear electronics methods. Ultimately, this digital data acquisition system will be expanded to incorporate the first coincidence measurements of Auger electron and annihilation gamma energies.

  14. Involvement of brain catalase activity in the acquisition of ethanol-induced conditioned place preference.

    Science.gov (United States)

    Font, Laura; Miquel, Marta; Aragon, Carlos M G

    2008-03-18

    It has been suggested that some of the behavioral effects produced by ethanol are mediated by its first metabolite, acetaldehyde. The present research addressed the hypothesis that catalase-dependent metabolism of ethanol to acetaldehyde in the brain is an important step in the production of ethanol-related affective properties. Firstly, we investigated the contribution of brain catalase in the acquisition of ethanol-induced conditioned place preference (CPP). Secondly, the specificity of the catalase inhibitor 3-amino-1,2,4-triazole (AT) was evaluated with morphine- and cocaine-induced CPP. Finally, to investigate the role of catalase in the process of relapse to ethanol seeking caused by re-exposure to ethanol, after an initial conditioning and extinction, mice were primed with saline and ethanol or AT and ethanol and tested for reinstatement of CPP. Conditioned place preference was blocked in animals treated with AT and ethanol. Morphine and cocaine CPP were unaffected by AT treatment. However, the reinstatement of place preference was not modified by catalase inhibition. Taken together, the results of the present study indicate that the brain catalase-H(2)O(2) system contributes to the acquisition of affective-dependent learning induced by ethanol, and support the involvement of centrally-formed acetaldehyde in the formation of positive affective memories produced by ethanol.

  15. HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

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    Doublier Sophie

    2012-01-01

    Full Text Available Abstract Background Invasive micropapillary carcinoma (IMPC of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1 activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. Methods HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. Results In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl-1-benzylindazole (a widely used HIF-1α inhibitor or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. Conclusions MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance.

  16. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    Science.gov (United States)

    Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Zhang, Y.; Karmakar, A.; Casciano, D.; Ali, S.; Biris, A.

    2013-02-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

  17. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    International Nuclear Information System (INIS)

    Mahmood, M; Xu, Y; Dantuluri, V; Mustafa, T; Karmakar, A; Casciano, D; Biris, A; Zhang, Y; Ali, S

    2013-01-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells. (paper)

  18. Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.

    1983-01-01

    A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning

  19. Phosphoproteome profiling reveals critical role of JAK-STAT signaling in maintaining chemoresistance in breast cancer

    NARCIS (Netherlands)

    Nascimento, A.S. (Augusto S.); Peres, L.L. (Luisa L.); Faria, A.V.S. (Alessandra V.S.); R. Milani (Renato); R.A. Fraga-Silva (Rodrigo); Fernandes, C.C. (Celio da Costa); M.P. Peppelenbosch (Maikel); Ferreira-Halder, C.V. (Carmen V.); W.F. Zambuzzi (Willian)

    2017-01-01

    textabstractBreast cancer is responsible for 25% of cancer cases and 15% of cancer death among women. Treatment is usually prolonged and hampered by the development of chemoresistance. The molecular mechanisms maintaining the chemoresistant phenotype remains, however, largely obscure. As kinase

  20. Phase II study of concomitant chemoradiotherapy in bulky refractory or chemoresistant relapsed lymphomas

    International Nuclear Information System (INIS)

    Girinsky, Theodore; Lapusan, Simona; Ribrag, Vincent; Koscielny, Serge; Ferme, Christophe; Carde, Patrice

    2005-01-01

    Purpose: To evaluate the local efficacy of concomitant chemoradiotherapy in patients with mostly refractory lymphoma. Methods and materials: Patients with refractory or chemoresistant-relapsed lymphoma and bulky life-threatening masses were included in this study. A split course of concomitant radiotherapy and chemotherapy (mostly cisplatin and etoposide) was delivered during a 6-week period. Weekly blood tests and a clinical examination using the Radiation Therapy Oncology Group guidelines were performed to assess acute toxicity. The tumor response was evaluated 1-3 months after treatment and at regular follow-up visits. Results: We enrolled 21 patients in the study between January 1998 and April 2003. Of the 21 patients, 60% had disseminated disease with bulky tumor masses and 85% had refractory lymphoma, of which most had been treated with at least two different chemotherapy regimens before concomitant chemoradiotherapy. Seventy-five percent received regimens containing cisplatinum and etoposide. The median radiation dose was 40 Gy (range, 12-62.5 Gy). Grade 3-4 hematologic toxicity and mucositis was observed in 70% and 30% of cases respectively, without any deaths. The overall response and complete remission rate was 70% and 20%, respectively. The 1-year overall survival and local progression-free survival rate was 20.4% and 54%, respectively. Three patients with localized disease were still alive 16, 33, and 48 months after treatment. Conclusion: Concomitant chemoradiotherapy for refractory or chemoresistant-relapsed lymphoma induced high hematologic toxicity, but seemed adequate for controlling local bulky tumor masses. No toxicity-related death was observed

  1. Studies on the role of central histamine in the acquisition of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1982-01-01

    The experiments described in this report were designed to test two hypotheses about how exposure to low-level radiation can affect the behavior of an organism: first, tht radiation effects on behavior are mediated by a radiation-induced release of histamine; and second, that this radiation-induced histamine release can exert relatively direct effects on the central nervous system. The results of the first experiment showed that microinjection of histamine directly into the fourth ventricle of rats produced a taste aversion to a novel sucrose solution. Pretreating rats with intraventricular H 1 or H 2 blockers was not effective in preventing the acquisition of the radiation-induced aversion, although the H 1 blocker did prevent the acquisition of a histamine-induced taste aversion. It also was not possible to establish a cross-tolerance between centrally administered histamine and radiation. The results are interpreted as not supporting the hypothesis that a radiation-induced release of central histamine mediates the acquisition of a conditioned taste aversion following exposure to low-level radiation

  2. CD133 expression in chemo-resistant Ewing sarcoma cells

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    Kovar Heinrich

    2010-03-01

    Full Text Available Abstract Background Some human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance. Methods Expression of the CD133-encoding PROM1 gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and in vivo tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl-5-(3-carboxy-methoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium assays. Results PROM1 expression was either absent or extremely low in most tumors. However, PROM1 was highly over-expressed in 4 of 48 cases. Two of the 4 patients with PROM1 over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of PROM1 in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny. Conclusions Up to 10% of ESFT express high levels of PROM1. In some tumors and cell

  3. The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0297 TITLE: The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma PRINCIPAL INVESTIGATOR: Vu Ngo...AND SUBTITLE The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma 5a. CONTRACT NUMBER The Role of Cyclin D1 in the Chemoresistance of...Mantle Cell Lymphoma 5b. GRANT NUMBER GRANT1173 9905 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Vu Ngo 5e. TASK NUMBER E

  4. Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.

    Science.gov (United States)

    Gomez-Miragaya, Jorge; González-Suárez, Eva

    2017-01-01

    Taxanes are mainstay treatment of triple negative breast cancer (TNBC) patients but resistance often develops. Using TNBC patient-derived orthoxenografts (PDX) we have recently discovered that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands in tumors that have acquired resistance. Importantly, sensitivity to taxanes is recovered after long-term drug interruption. The characterization of this chemoresistant CD49f+ cells provides a unique opportunity to identify novel targets for the treatment of chemoresistant TNBC.

  5. Prereader to beginning reader: changes induced by reading acquisition in print and speech brain networks.

    Science.gov (United States)

    Chyl, Katarzyna; Kossowski, Bartosz; Dębska, Agnieszka; Łuniewska, Magdalena; Banaszkiewicz, Anna; Żelechowska, Agata; Frost, Stephen J; Mencl, William Einar; Wypych, Marek; Marchewka, Artur; Pugh, Kenneth R; Jednoróg, Katarzyna

    2018-01-01

    Literacy acquisition is a demanding process that induces significant changes in the brain, especially in the spoken and written language networks. Nevertheless, large-scale paediatric fMRI studies are still limited. We analyzed fMRI data to show how individual differences in reading performance correlate with brain activation for speech and print in 111 children attending kindergarten or first grade and examined group differences between a matched subset of emergent-readers and prereaders. Across the entire cohort, individual differences analysis revealed that reading skill was positively correlated with the magnitude of activation difference between words and symbol strings in left superior temporal, inferior frontal and fusiform gyri. Group comparisons of the matched subset of pre- and emergent-readers showed higher activity for emergent-readers in left inferior frontal, precentral, and postcentral gyri. Individual differences in activation for natural versus vocoded speech were also positively correlated with reading skill, primarily in the left temporal cortex. However, in contrast to studies on adult illiterates, group comparisons revealed higher activity in prereaders compared to readers in the frontal lobes. Print-speech coactivation was observed only in readers and individual differences analyses revealed a positive correlation between convergence and reading skill in the left superior temporal sulcus. These results emphasise that a child's brain undergoes several modifications to both visual and oral language systems in the process of learning to read. They also suggest that print-speech convergence is a hallmark of acquiring literacy. © 2017 Association for Child and Adolescent Mental Health.

  6. Chemoresistance of human monocyte-derived dendritic cells is regulated by IL-17A.

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    Selma Olsson Åkefeldt

    Full Text Available Dendritic cells initiate adaptive immune responses, leading either to control cancer by effector T cells or to exacerbate cancer by regulatory T cells that inhibit IFN-γ-mediated Th1-type response. Dendritic cells can also induce Th17-type immunity, mediated by IL-17A. However, the controversial role of this cytokine in cancer requires further investigations. We generated dendritic cells from peripheral blood monocytes to investigate lifespan, phenotype and chemoresistance of dendritic cells, treated with IL-17A with or without IFN-γ. Studying the expression of Bcl-2 family members, we demonstrated that dendritic cells constitutively express one pro-survival Bcl-2 member: MCL1. Immature dendritic cells were CD40(lowHLADR(low CD1a(+ MCL1(+, did not express CD14, CD68 or BCL2A1, and displayed a short 2-day lifespan. IL-17A-treated DC exhibited a semi-mature (CD40(high HLADR(low pre-M2 (CCL22(+ CD206(+ CD163(+ IL1RN(+ IL-10(- CXCL10(- IL-12(- mixed (CD1a(+ CD14+ CD68(+ macrophage-dendritic cell phenotype. They efficiently exerted mannose receptor-mediated endocytosis and did not produce superoxide anions, in the absence of TLR engagement. Interestingly, IL-17A promoted a long-term survival of dendritic cells, beyond 12 days, that correlated to BCL2A1 induction, a pro-survival Bcl-2 family member. BCL2A1 transcription was activated by NF-κB, downstream of IL-17A transduction. Thus, immature dendritic cells only express MCL1, whereas IL-17A-treated dendritic cells concomitantly expressed two pro-survival Bcl-2 family members: MCL1 and BCL2A1. These latter developed chemoresistance to 11 of the 17 chemotherapy agents tested. However, high doses of either vinblastine or cytarabine decreased MCL1 expression and induced dendritic cell death. When IL-17A is produced in vivo, administration of anti-IL-17A biotherapy may impair dendritic cell survival by targeting BCL2A1 expression. Consequently, depending on the effector or regulatory role of dendritic

  7. Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer

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    Xiang Yang

    2017-10-01

    Full Text Available Background/Aims: Although small cell lung cancer (SCLC is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.

  8. Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance

    Directory of Open Access Journals (Sweden)

    Gorka Ruiz de Garibay

    2018-05-01

    Full Text Available Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs, we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2 is associated with this process. A triple-negative BRCA1-mutated PDX was used to study the genetics of chemoresistance. The PDX was treated in parallel with four chemotherapies for five iterative cycles. Exome sequencing identified few genes with de novo or enriched mutations in common among the different therapies, whereas many common depleted mutations/genes were observed. Analysis of somatic mutations from The Cancer Genome Atlas (TCGA supported the prognostic relevance of the identified genes. A mutation in TCF4 was found de novo in all treatments, and analysis of drug sensitivity profiles across cancer cell lines supported the link to chemoresistance. Loss of TCF4 conferred chemoresistance in breast cancer cell models, possibly by altering cell cycle regulation. Targeted sequencing in chemoresistant tumors identified an intronic variant of TCF4 that may represent an expression quantitative trait locus associated with relapse outcome in TCGA. Immunohistochemical studies suggest a common loss of nuclear TCF4 expression post-chemotherapy. Together, these results from tumor xenograft modeling depict a link between altered TCF4 expression and breast cancer chemoresistance.

  9. Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10.

    Science.gov (United States)

    Stern, Louisa; Giese, Nathalia; Hackert, Thilo; Strobel, Oliver; Schirmacher, Peter; Felix, Klaus; Gaida, Matthias M

    2018-01-01

    Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines. Caffeine, a known ligand for T2R10, rendered the tumor cells more susceptible to two standard chemotherapeutics, Gemcitabine and 5-Fluoruracil. Knocking down T2R10 in the cell line BxPC-3 reduced the caffeine-induced effect. As possible underlying mechanism, we found that caffeine via triggering T2R10 inhibited Akt phosphorylation and subsequently downregulated expression of ABCG2, the so-called multi-drug resistance protein that participates in rendering cells resistant to a variety of chemotherapeutics. In conclusion, T2R10 is expressed in pancreatic cancer and it downmodulates the chemoresistance of the tumor cells.

  10. Increase of glucocorticoids is not required for the acquisition, but hinders the extinction, of lithium-induced conditioned taste aversion.

    Science.gov (United States)

    Kim, Kyu-Nam; Kim, Bom-Taeck; Kim, Young-Sang; Lee, Jong-Ho; Jahng, Jeong Won

    2014-05-05

    Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

    2016-07-01

    The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

  12. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    International Nuclear Information System (INIS)

    Díaz-Montero, C Marcela; McIntyre, Bradley W

    2005-01-01

    Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well. Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators

  13. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  14. Interaction of translationally controlled tumor protein with Apaf-1 is involved in the development of chemoresistance in HeLa cells

    International Nuclear Information System (INIS)

    Jung, Jaehoon; Kim, Hyo Young; Maeng, Jeehye; Kim, Moonhee; Shin, Dong Hae; Lee, Kyunglim

    2014-01-01

    Translationally controlled tumor protein (TCTP), alternatively called fortilin, is believed to be involved in the development of the chemoresistance of tumor cells against anticancer drugs such as etoposide, taxol, and oxaliplatin, the underlying mechanisms of which still remain elusive. Cell death analysis of TCTP-overexpressing HeLa cells was performed following etoposide treatment to assess the mitochondria-dependent apoptosis. Apoptotic pathway was analyzed through measuring the cleavage of epidermal growth factor receptor (EGFR) and phospholipase C-γ (PLC-γ), caspase activation, mitochondrial membrane perturbation, and cytochrome c release by flow cytometry and western blotting. To clarify the role of TCTP in the inhibition of apoptosome, in vitro apoptosome reconstitution and immunoprecipitation was used. Pull-down assay and silver staining using the variants of Apaf-1 protein was applied to identify the domain that is responsible for its interaction with TCTP. In the present study, we confirmed that adenoviral overexpression of TCTP protects HeLa cells from cell death induced by cytotoxic drugs such as taxol and etoposide. TCTP antagonized the mitochondria-dependent apoptotic pathway following etoposide treatment, including mitochondrial membrane damage and resultant cytochrome c release, activation of caspase-9, and -3, and eventually, the cleavage of EGFR and PLC-γ. More importantly, TCTP interacts with the caspase recruitment domain (CARD) of Apaf-1 and is incorporated into the heptameric Apaf-1 complex, and that C-terminal cleaved TCTP specifically associates with Apaf-1 of apoptosome in apoptosome-forming condition thereby inhibiting the amplification of caspase cascade. TCTP protects the cancer cells from etoposide-induced cell death by inhibiting the mitochondria-mediated apoptotic pathway. Interaction of TCTP with Apaf-1 in apoptosome is involved in the molecular mechanism of TCTP-induced chemoresistance. These findings suggest that TCTP may serve

  15. Sexual harassment induces a temporary fitness cost but does not constrain the acquisition of environmental information in fruit flies.

    Science.gov (United States)

    Teseo, Serafino; Veerus, Liisa; Moreno, Céline; Mery, Frédéric

    2016-01-01

    Across animals, sexual harassment induces fitness costs for females and males. However, little is known about the cognitive costs involved, i.e. whether it constrains learning processes, which could ultimately affect an individual's fitness. Here we evaluate the acquisition of environmental information in groups of fruit flies challenged with various levels of male sexual harassment. We show that, although high sexual harassment induces a temporary fitness cost for females, all fly groups of both sexes exhibit similar levels of learning. This suggests that, in fruit flies, the fitness benefits of acquiring environmental information are not affected by the fitness costs of sexual harassment, and that selection may favour cognition even in unfavourable social contexts. Our study provides novel insights into the relationship between sexual conflicts and cognition and the evolution of female counterstrategies against male sexual harassment. © 2016 The Author(s).

  16. Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition.

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

    It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  17. Amygdala’s involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition

    Directory of Open Access Journals (Sweden)

    Lily S Chau

    2012-10-01

    Full Text Available It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala’s role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS is paired with a salient unconditioned stimulus (US that elicits an unconditioned response (UR. After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR. Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala’s involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  18. Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

    Science.gov (United States)

    Dzobo, Kevin; Hassen, Naseeha; Senthebane, Dimakatso Alice; Thomford, Nicholas Ekow; Rowe, Arielle; Shipanga, Hendrina; Wonkam, Ambroise; Parker, M Iqbal; Mowla, Shaheen; Dandara, Collet

    2018-04-17

    Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells.

  19. Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance.

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Alt, Andreas; Miltner, Erich

    2008-08-01

    The therapeutic opioid drug methadone (d,l-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-x(L) and X chromosome-linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug-sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.

  20. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    International Nuclear Information System (INIS)

    Pu, Jun; Bai, Danna; Yang, Xia; Lu, Xiaozhao; Xu, Lijuan; Lu, Jianguo

    2012-01-01

    Highlights: ► Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. ► Adrenaline activates NFκB in a dose dependent manner. ► NFκB–miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NFκB dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline–NFκB–miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  1. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    Energy Technology Data Exchange (ETDEWEB)

    Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  2. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance.

    Science.gov (United States)

    Lobb, Richard J; van Amerongen, Rosa; Wiegmans, Adrian; Ham, Sunyoung; Larsen, Jill E; Möller, Andreas

    2017-08-01

    Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited treatment options and poor patient survival. NSCLCs are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known. We hypothesised that small extracellular vesicles, exosomes, secreted by mesenchymal NSCLC cells could potentially transfer the chemoresistance phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we used a unique human bronchial epithelial cell (HBEC) model in which the parental cells were transformed from an epithelial to mesenchymal phenotype by introducing oncogenic alterations common in NSCLC. We found that exosomes derived from the oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription factor, in the recipient cells. Additionally, we demonstrate that exosomes from mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a potential mechanism for the induction of a mesenchymal phenotype in recipient cells. Together, this work demonstrates for the first time that exosomes derived from mesenchymal, oncogenically transformed lung cells can transfer chemoresistance and mesenchymal phenotypes to recipient cells, likely via the transfer of ZEB1 mRNA in exosomes. © 2017 UICC.

  3. Integrin β1, osmosensing, and chemoresistance in mouse ehrlich carcinoma cells

    DEFF Research Database (Denmark)

    Sørensen, Belinda Halling; Rasmussen, Line Jee Hartmann; Broberg, Bjørn Sindballe

    2015-01-01

    BACKGROUND/AIMS: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell ...

  4. Evaluation of Anti-tumor and Chemoresistance-lowering Effects of ...

    African Journals Online (AJOL)

    Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer. Mingqian Lu, Xinhua Xu, Hongda Lu, Zhongxin Lu, Bingqing Xu, Chao Tan, Kezhi Shi, Rong Guo, Qingzhi Kong ...

  5. Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype

    Directory of Open Access Journals (Sweden)

    Berry Nicholas B

    2008-11-01

    Full Text Available Abstract Aggressive epithelial ovarian cancer (EOC is genetically and epigenetically distinct from normal ovarian surface epithelial cells (OSE and early neoplasia. Co-expression of epithelial and mesenchymal markers in EOC suggests an involvement of epithelial-mesenchymal transition (EMT in cancer initiation and progression. This phenomenon is often associated with acquisition of a stem cell-like phenotype and chemoresistance that correlate with the specific gene expression patterns accompanying transformation, revealing a plasticity of the ovarian cancer cell genome during disease progression. Differential gene expressions between normal and transformed cells reflect the varying mechanisms of regulation including genetic changes like rearrangements within the genome, as well as epigenetic changes such as global genomic hypomethylation with localized promoter CpG island hypermethylation. The similarity of gene expression between ovarian cancer cells and the stem-like ovarian cancer initiating cells (OCIC are surprisingly also correlated with epigenetic mechanisms of gene regulation in normal stem cells. Both normal and cancer stem cells maintain genetic flexibility by co-placement of activating and/or repressive epigenetic modifications on histone H3. The co-occupancy of such opposing histone marks is believed to maintain gene flexibility and such bivalent histones have been described as being poised for transcriptional activation or epigenetic silencing. The involvement of both-microRNA (miRNA mediated epigenetic regulation, as well as epigenetic-induced changes in miRNA expression further highlight an additional complexity in cancer stem cell epigenomics. Recent advances in array-based whole-genome/epigenome analyses will continue to further unravel the genomes and epigenomes of cancer and cancer stem cells. In order to illuminate phenotypic signatures that delineate ovarian cancer from their associated cancer stem cells, a priority must lie

  6. Field Trials of the Multi-Source Approach for Resistivity and Induced Polarization Data Acquisition

    Science.gov (United States)

    LaBrecque, D. J.; Morelli, G.; Fischanger, F.; Lamoureux, P.; Brigham, R.

    2013-12-01

    Implementing systems of distributed receivers and transmitters for resistivity and induced polarization data is an almost inevitable result of the availability of wireless data communication modules and GPS modules offering precise timing and instrument locations. Such systems have a number of advantages; for example, they can be deployed around obstacles such as rivers, canyons, or mountains which would be difficult with traditional 'hard-wired' systems. However, deploying a system of identical, small, battery powered, transceivers, each capable of injecting a known current and measuring the induced potential has an additional and less obvious advantage in that multiple units can inject current simultaneously. The original purpose for using multiple simultaneous current sources (multi-source) was to increase signal levels. In traditional systems, to double the received signal you inject twice the current which requires you to apply twice the voltage and thus four times the power. Alternatively, one approach to increasing signal levels for large-scale surveys collected using small, battery powered transceivers is it to allow multiple units to transmit in parallel. In theory, using four 400 watt transmitters on separate, parallel dipoles yields roughly the same signal as a single 6400 watt transmitter. Furthermore, implementing the multi-source approach creates the opportunity to apply more complex current flow patterns than simple, parallel dipoles. For a perfect, noise-free system, multi-sources adds no new information to a data set that contains a comprehensive set of data collected using single sources. However, for realistic, noisy systems, it appears that multi-source data can substantially impact survey results. In preliminary model studies, the multi-source data produced such startling improvements in subsurface images that even the authors questioned their veracity. Between December of 2012 and July of 2013, we completed multi-source surveys at five sites

  7. Rhodiola rosea Impairs Acquisition and Expression of Conditioned Place Preference Induced by Cocaine

    OpenAIRE

    Federica Titomanlio; Carmen Manzanedo; Marta Rodríguez-Arias; Laura Mattioli; Marina Perfumi; José Miñarro; María A. Aguilar

    2013-01-01

    A novel approach to the treatment of adverse effects of drugs of abuse is one which makes use of natural products. The present study investigated the effect of Rhodiola rosea L. hydroalcoholic extract (RHO) on cocaine-induced hyperactivity and conditioned place preference (CPP) in mice. In a first experiment, mice received RHO (15, 20 or 25?mg/kg, IG), cocaine (25?mg/kg, i.p.) (COC), or a combination of both drugs (COC + RHO15, COC + RHO20, and COC + RHO25), and their locomotor activity was e...

  8. Laser induced ultrasonic phased array using full matrix capture data acquisition and total focusing method.

    Science.gov (United States)

    Stratoudaki, Theodosia; Clark, Matt; Wilcox, Paul D

    2016-09-19

    Laser ultrasonics is a technique where lasers are employed to generate and detect ultrasound. A data collection method (full matrix capture) and a post processing imaging algorithm, the total focusing method, both developed for ultrasonic arrays, are modified and used in order to enhance the capabilities of laser ultrasonics for nondestructive testing by improving defect detectability and increasing spatial resolution. In this way, a laser induced ultrasonic phased array is synthesized. A model is developed and compared with experimental results from aluminum samples with side drilled holes and slots at depths of 5 - 20 mm from the surface.

  9. Acquisition of lipid metabolic capability in hepatocyte-like cells directly induced from mouse fibroblasts

    Directory of Open Access Journals (Sweden)

    Shizuka eMiura

    2014-08-01

    Full Text Available Recently, the numbers of patients with non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH have increased worldwide. NAFLD and NASH are known as risk factors for liver cirrhosis and hepatocellular carcinoma. Because many factors can promote the progression of NAFLD and NASH, the treatment of these patients involves various strategies. Thus, it is desired that drugs for patients with NAFLD and NASH should be developed more easily and rapidly using cultures of primary hepatocytes. However, it is difficult to use hepatocytes as a tool for drug screening, because these cells cannot be functionally maintained in culture. Thus, in this study, we sought to examine whether induced hepatocyte-like (iHep cells, which were directly induced from mouse dermal fibroblasts by infection with a retrovirus expressing Hnf4α and Foxa3, possess the potential for lipid metabolism, similar to hepatocytes. Our data showed that iHep cells were capable of synthesizing lipids from a cis-unsaturated fatty acid, a trans-unsaturated fatty acid, and a saturated fatty acid, accumulating the synthesized lipids in cellular vesicles, and secreting the lipids into the culture medium. Moreover, the lipid synthesis in iHep cells was significantly inhibited in cultures with lipid metabolism improvers. These results demonstrate that iHep cells could be useful not only for screening of drugs for patients with NAFLD and NASH, but also for elucidation of the mechanisms underlying hereditary lipid metabolism disorders, as an alternative to hepatocytes.

  10. Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities

    International Nuclear Information System (INIS)

    Marfels, Christian; Hoehn, Miriam; Wagner, Ernst; Günther, Michael

    2013-01-01

    Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments a better understanding of biochemical changes in the resistant tumors is needed. In this study, we focus on the characterization of in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft model. SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR and in endothelial transdifferentiation studies on matrigel. HUH-REISO cells, although slightly more sensitive against activated CPA in vitro than parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged without chemotherapeutic pressure) revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A comparative study on stemness and plasticity markers revealed upregulation of Thy-1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression. Chemoresistance of HUH-REISO was not manifested under standard in vitro but under in vivo conditions. HUH-REISO cells showed

  11. Implication of chemo-resistant memory T cells for immune surveillance in patients with sarcoma receiving chemotherapy.

    Science.gov (United States)

    Shibayama, Yuji; Tsukahara, Tomohide; Emori, Makoto; Murata, Kenji; Mizushima, Emi; Hirohashi, Yoshihiko; Kanaseki, Takayuki; Nakatsugawa, Munehide; Kubo, Terufumi; Yamashita, Toshihiko; Sato, Noriyuki; Torigoe, Toshihiko

    2017-09-01

    Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8 + memory T cell population with a chemo-resistance property, "young memory" T (T YM ) cells. In this study, we investigated the proportion and function of T YM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of T YM cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only T YM cells but also T CM and T EM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from T YM , T CM and T EM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from T YM cells but were hardly induced from T EM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from T YM cells but not from the T CM and T EM cells in sarcoma patients who received chemotherapy. The findings suggest that T YM cells are resistant to chemotherapy and can firstly recover from the nadir. T YM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. A response strategy predicts acquisition of schedule-induced polydipsia in rats.

    Science.gov (United States)

    Gregory, James Gardner; Hawken, Emily R; Banasikowski, Tomek J; Dumont, Eric C; Beninger, Richard J

    2015-08-03

    Schedule-induced polydipsia (SIP) is excessive, non-regulatory drinking. We aimed to identify phenotypic learning traits representative of neural circuitry that underlies SIP and hypothesized that rats that are response-learners will be more susceptible in developing compulsive water drinking. Using the Y-maze, the rats were characterized as either place- or response-learners. They were exposed to the SIP protocol for a period of 21days. Subsequent histological staining for FosB/ΔFosB examined neuronal activation associated with SIP in several brain regions. The rats with a preference for a response-learning strategy were more likely to develop SIP than the rats using a place-learning strategy. Furthermore amphetamine sensitization, observed to increase SIP, also shifted learning strategy to a response-learning strategy. No differences were observed in FosB/ΔFosB expression between SIP and non-SIP rats in the dorsolateral striatum (DLS) and CA1 region of the hippocampus. However, SIP rats had greater FosB/ΔFosB expression in prefrontal cortex regions. The rats that develop SIP have a preference for response-learning strategies and increased neuronal activation in frontal cortical regions associated with habit formation and compulsion. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

    Science.gov (United States)

    Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

    2012-01-01

    Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

  14. Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration.

    Science.gov (United States)

    Blacktop, Jordan M; Todd, Ryan P; Sorg, Barbara A

    2017-05-15

    Addiction involves drug-induced neuroplasticity in the circuitry of motivated behavior, which includes the medial forebrain bundle and the lateral hypothalamic area. Emerging at the forefront of neuroplasticity regulation are specialized extracellular matrix (ECM) structures that form perineuronal nets (PNNs) around certain neurons, mainly parvalbumin positive (PV + ), fast-spiking interneurons (FSINs), making them a promising target for the regulation of drug-induced neuroplasticity. Despite the emerging significance of PNNs in drug-induced neuroplasticity and the well-established role of the lateral hypothalamic area (LHA) in reward, reinforcement, and motivation, very little is known about how PNN-expressing neurons control drug-seeking behavior. We found that a discrete region of the anterior dorsal LHA (LHAad) exhibited robust PNN and dense ECM expression. Approximately 87% of parvalbumin positive (PV + ) neurons co-expressed the PNN marker Wisteria floribunda agglutinin (WFA), while 62% of WFA positive (WFA + ) neurons co-expressed PV in the LHAad of drug naïve rats. Removal of PNNs within this brain region via chrondroitinase ABC (Ch-ABC) administration abolished acquisition of cocaine-induced CPP and significantly attenuated the acquisition of cocaine self-administration (SA). Removal of LHAad PNNs did not affect locomotor activity, sucrose intake, sucrose-induced CPP, or acquisition of sucrose SA in separate groups of cocaine naïve animals. These data suggest that PNN-dependent neuroplasticity within the LHAad is critical for the acquisition of both cocaine-induced CPP and SA but is not general to all rewards, and that PNN degradation may have utility for the management of drug-associated behavioral plasticity and memory in cocaine addicts. Published by Elsevier Ltd.

  15. Tumor initiating cells and chemoresistance: which is the best strategy to target colon cancer stem cells?

    Science.gov (United States)

    Paldino, Emanuela; Tesori, Valentina; Casalbore, Patrizia; Gasbarrini, Antonio; Puglisi, Maria Ausiliatrice

    2014-01-01

    There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called "cancer stem cells" (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  16. Effect of Dietary Induced Metabolic Acidosis on Bone Mineral Acquisition in 2-8 Month Old Lambs

    Directory of Open Access Journals (Sweden)

    E.S. Hackett

    2009-01-01

    induced MA that resulted in a significant decrease in bone mineral acquisition in juvenile sheep. Diets that induce MA may have a profound impact on lowering peak BMD in adolescents and therefore predispose individuals to osteoporosis later in life.

  17. The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

    Science.gov (United States)

    Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-07-28

    Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Large 3D resistivity and induced polarization acquisition using the Fullwaver system: towards an adapted processing methodology

    Science.gov (United States)

    Truffert, Catherine; Leite, Orlando; Gance, Julien; Texier, Benoît; Bernard, Jean

    2017-04-01

    Driven by needs in the mineral exploration market for ever faster and ever easier set-up of large 3D resistivity and induced polarization, autonomous and cableless recorded systems come to the forefront. Opposite to the traditional centralized acquisition, this new system permits a complete random distribution of receivers on the survey area allowing to obtain a real 3D imaging. This work presents the results of a 3 km2 large experiment up to 600m of depth performed with a new type of autonomous distributed receivers: the I&V-Fullwaver. With such system, all usual drawbacks induced by long cable set up over large 3D areas - time consuming, lack of accessibility, heavy weight, electromagnetic induction, etc. - disappear. The V-Fullwavers record the entire time series of voltage on two perpendicular axes, for a good determination of the data quality although I-Fullwaver records injected current simultaneously. For this survey, despite good assessment of each individual signal quality, on each channel of the set of Fullwaver systems, a significant number of negative apparent resistivity and chargeability remains present in the dataset (around 15%). These values are commonly not taken into account in the inversion software although they may be due to complex geological structure of interest (e.g. linked to the presence of sulfides in the earth). Taking into account that such distributed recording system aims to restitute the best 3D resistivity and IP tomography, how can 3D inversion be improved? In this work, we present the dataset, the processing chain and quality control of a large 3D survey. We show that the quality of the data selected is good enough to include it into the inversion processing. We propose a second way of processing based on the modulus of the apparent resistivity that stabilizes the inversion. We then discuss the results of both processing. We conclude that an effort could be made on the inclusion of negative apparent resistivity in the inversion

  19. Early-life adversity facilitates acquisition of cocaine self-administration and induces persistent anhedonia

    Directory of Open Access Journals (Sweden)

    Jessica L. Bolton

    2018-02-01

    Full Text Available Early-life adversity increases the risk for emotional disorders such as depression and schizophrenia. Anhedonia, thought to be a core feature of these disorders, is provoked by our naturalistic rodent model of childhood adversity (i.e., rearing pups for one week in cages with limited bedding and nesting, LBN. Drug use and addiction are highly comorbid with psychiatric disorders featuring anhedonia, yet effects of LBN on drug-seeking behavior and the reward and stress-related circuits that underlie it remain unknown. Here we examined the effects of LBN on cocaine intake and seeking, using a battery of behavioral tests measuring distinct aspects of cocaine reward, and for comparison, chocolate intake. We also examined activation of neurons within the pleasure/reward and stress circuits following cocaine in LBN and control rats. Early-life adversity reduced spontaneous intake of palatable chocolate, extending prior reports of sucrose and social-play anhedonia. In a within-session cocaine behavioral economic test, LBN rats self-administered lower dosages of cocaine under low-effort conditions, consistent with a reduced hedonic set-point for cocaine, and potentially anhedonia. In contrast, cocaine demand elasticity was not consistently affected, indicating no major changes in motivation to maintain preferred cocaine blood levels. These changes were selective, as LBN did not cause an overt anxiety-like phenotype, nor did it affect sensitivity to self-administered cocaine dose, responding for cocaine under extinction conditions, cocaine- or cue-induced reinstatement of cocaine seeking, or locomotor response to acute cocaine. However, high Fos expression was seen after cocaine in both reward- and stress-related brain regions of LBN rats, including nucleus accumbens core, central amygdala, and lateral habenula. In contrast, hypothalamic orexin neuron activation after cocaine was significantly attenuated in LBN rats. Together, these findings demonstrate

  20. New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance.

    Science.gov (United States)

    Monderer, David; Luseau, Alexandrine; Bellec, Amélie; David, Emmanuelle; Ponsolle, Stéphanie; Saiagh, Soraya; Bercegeay, Sylvain; Piloquet, Philippe; Denis, Marc G; Lodé, Laurence; Rédini, Françoise; Biger, Marine; Heymann, Dominique; Heymann, Marie-Françoise; Le Bot, Ronan; Gouin, François; Blanchard, Frédéric

    2013-10-01

    Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies to study their chemoresistance. Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for cell culture and transplantation into nude mice. Only one transplanted biopsy and one injected cell line has engrafted successfully leading to conventional central high-grade chondrosarcoma similar to the original biopsies. In culture, two new stable cell lines were obtained, one from a dedifferentiated and one from a grade III conventional central chondrosarcoma biopsy. Their genetic characterization revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high-throughput quantitative RT-PCR approach, we observed that cell lines cultured in monolayer had lost expression of several genes implicated in cartilage development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures. Chondrosarcoma cells in monolayer were sensitive to several conventional chemotherapeutic agents but became resistant to low doses of mafosfamide or doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic accumulation of the drug. Our results indicate that the cartilaginous matrix produced by chondrosarcoma cells may impair diffusion of several drugs and thus contribute to chemoresistance

  1. Replication fork stability confers chemoresistance in BRCA-deficient cells

    DEFF Research Database (Denmark)

    Chaudhuri, Arnab Ray; Callen, Elsa; Ding, Xia

    2016-01-01

    /4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11......Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3...... nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations...

  2. miR-340 alleviates chemoresistance of osteosarcoma cells by targeting ZEB1.

    Science.gov (United States)

    Yan, Haibin; Zhang, Bingyun; Fang, Chongbin; Chen, Liqiu

    2018-06-01

    Chemoresistance during treatment of osteosarcoma (OS) is attracting more and more attention as the main clinical obstacle. The purpose of this study was to elucidate the role of miR-340 in chemoresistance of OS. Plasmid construction and transfection, miRNA arrays, PCR analyses, and western blot analysis, as well as MTT, apoptosis, and luciferase assays were carried out in MG-63 cells and MG-63/cisplatin (DDP)-resistant cells. The results showed that miR-340 was downregulated in OS tissues and drug-resistant OS cells. Moreover, a negative correlation was observed between miR-340 and ZEB1 expression in OS tissues. Forced expression of miR-340 in drug-resistant OS cells significantly reduced multidrug resistance-1 and P-gp expression. Overexpression of miR-340 enhanced sensitivity to DDP by inhibiting viability and promoting apoptosis. The luciferase assay and western blot analysis identified ZEB1 as a direct target of miR-340, and miR-340 negatively regulated ZEB1 expression. Ectopic expression of ZEB1 reversed the effects of miR-340 on P-gp expression, cell viability, and apoptosis. miR-340 alleviated chemoresistance of OS cells by targeting ZEB1. Our results indicate that targeting miR-340 may be a potential therapeutic approach to treat drug-resistant OS.

  3. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

  4. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    International Nuclear Information System (INIS)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M.; Blackman, G.

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received αIFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. αIFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance αIFN therapy could not be fully evaluated. (author)

  5. Molecular Checkpoint Decisions Made by Subverted Vascular Niche Transform Indolent Tumor Cells into Chemoresistant Cancer Stem Cells.

    Science.gov (United States)

    Cao, Zhongwei; Scandura, Joseph M; Inghirami, Giorgio G; Shido, Koji; Ding, Bi-Sen; Rafii, Shahin

    2017-01-09

    Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R). However, chemotherapy triggers TECs to suppress IGFBP7, and this stimulates IGF1R + TSCs to express FGF4, inducing a feedforward FGFR1-ETS2 angiocrine cascade that obviates TEC IGFBP7. Thus, loss of IGFBP7 and upregulation of IGF1 activates the FGF4-FGFR1-ETS2 pathway in TECs and converts naive tumor cells to chemoresistant TSCs, thereby facilitating their invasiveness and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    Science.gov (United States)

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  7. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  8. Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway.

    Directory of Open Access Journals (Sweden)

    Saurabh Singh

    Full Text Available Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treatment drugs like paclitaxel (PTX ineffective. The present study aims to determine the role of miRNAs and Hedgehog (Hh pathway in chemoresistant prostate cancer and to evaluate the combination therapy using Hh inhibitor cyclopamine (CYA. Studies were conducted on PTX resistant DU145-TXR and PC3-TXR cell lines and clinical prostate tissues. Drug sensitivity and apoptosis assays showed significantly improved cytotoxicity with combination of PTX and CYA. To distinguish the presence of cancer stem cell like side populations (SP, Hoechst 33342 flow cytometry method was used. PTX resistant DU145 and PC3 cells, as well as human prostate cancer tissue possess a distinct SP fraction. Nearly 75% of the SP cells are in the G0/G1 phase compared to 62% for non-SP cells and have higher expression of stem cell markers as well. SP cell fraction was increased following PTX monotherapy and treatment with CYA or CYA plus PTX effectively reduced their numbers suggesting the effectiveness of combination therapy. SP fraction cells were allowed to differentiate and reanalyzed by Hoechst staining and gene expression analysis. Post differentiation, SP cells constitute 15.8% of total viable cells which decreases to 0.6% on treatment with CYA. The expression levels of P-gp efflux protein were also significantly decreased on treatment with PTX and CYA combination. MicroRNA profiling of DU145-TXR and PC3-TXR cells and prostate cancer tissue from the patients showed decreased expression of tumor suppressor miRNAs such as miR34a and miR200c. Treatment with PTX and CYA combination restored the expression of miR200c and 34a, confirming their role in modulating chemoresistance. We have shown that supplementing mitotic stabilizer drugs such as PTX with Hh-inhibitor CYA can reverse PTX chemoresistance and eliminate SP fraction in androgen independent, metastatic prostate cancer cell

  9. CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

    Directory of Open Access Journals (Sweden)

    Ruijie Zhang

    2017-09-01

    Full Text Available Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1 is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

  10. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

    Science.gov (United States)

    Ahmed, Muhammad S.; Rainer, Carolyn; Nielsen, Sebastian R.; Quaranta, Valeria; Weyer-Czernilofsky, Ulrike; Engle, Danielle D.; Perez-Mancera, Pedro A.; Coupland, Sarah E.; Taktak, Azzam; Bogenrieder, Thomas; Tuveson, David A.; Campbell, Fiona; Schmid, Michael C.; Mielgo, Ainhoa

    2017-01-01

    Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. PMID:27742686

  11. Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?

    Directory of Open Access Journals (Sweden)

    Emanuela Paldino

    2014-01-01

    Full Text Available There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called “cancer stem cells” (CSCs. In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  12. Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer.

    Science.gov (United States)

    Garajová, Ingrid; Le Large, Tessa Y; Frampton, Adam E; Rolfo, Christian; Voortman, Johannes; Giovannetti, Elisa

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

  13. Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ingrid Garajová

    2014-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells. However, the recent discovery of microRNAs (miRNAs has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

  14. Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

    Science.gov (United States)

    Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

    2014-07-15

    The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Madhumathy G.; Desai, Krisha; Prabhu, Jyothi S.; Hari, P.S.; Remacle, Jose; Sridhar, T.S., E-mail: tssridhar@sjri.res.in

    2016-08-01

    Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells. Drug efflux based mechanisms do not contribute to this effect. We show that integrin β3 employs the PI3K-Akt and the MAPK pathway for enabling cell survival and proliferation. Further, our results indicate that integrin β3 helps inhibit epirubicin induced cytotoxicity by repression of the pro-apoptotic protein BAD, thus promoting an anti-apoptotic response. Myristoylated RGT peptide and a monoclonal antibody against integrin β3 brought about a reversal of this effect and chemosensitized the cells. These results identify β3 integrin signaling via repression of BAD as an important survival pathway used by breast cancer cells to evade chemotherapy induced stress. - Highlights: • Integrin β3 signaling promotes chemoresistance to epirubicin in breast cancer cells. • Integrin β3 promotes cell survival and proliferation in drug treated cells through the PI3K and MAPK pathways. • Integrin signaling helps evade drug induced cytotoxicity by repression of pro-apoptotic molecule; BAD.

  16. Effects of hypoxia on expression of a panel of stem cell and chemoresistance markers in glioblastoma-derived spheroids

    DEFF Research Database (Denmark)

    Kolenda, Jesper; Jensen, Stine Skov; Aaberg-Jessen, Charlotte

    2011-01-01

    ). Spheroids were formed in 21% and 1% O(2) in serum-free medium. The immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67), and stem cell markers (CD133, podoplanin, Bmi-1, nestin, Sox-2) as well as markers related to chemoresistance (MGMT, TIMP-1, Lamp-1, MRP1, MDR-1...

  17. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients

    International Nuclear Information System (INIS)

    Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre; Cohen, Simy; Perrot, Jean-Yves; Faussat, Anne-Marie; Zuany-Amorim, Claudia; Marjanovic, Zora; Morjani, Hamid; Fava, Fanny; Corre, Elise

    2009-01-01

    AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML). This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays. P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC 50 > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells. P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633

  18. Data acquisition

    International Nuclear Information System (INIS)

    Clout, P.N.

    1982-01-01

    Data acquisition systems are discussed for molecular biology experiments using synchrotron radiation sources. The data acquisition system requirements are considered. The components of the solution are described including hardwired solutions and computer-based solutions. Finally, the considerations for the choice of the computer-based solution are outlined. (U.K.)

  19. Utilizing the response patterns of a temperature modulated chemoresistive gas sensor for gas diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Amini, Amir [Jannatabad College, Sama Organization, Islamic Azad University, Tehran (Iran, Islamic Republic of); Ghafarinia, Vahid, E-mail: amir.amini.elec@gmail.com, E-mail: ghafarinia@ee.kntu.ac.ir [Electrical Engineering Department, K. N. Toosi University of Technology, Tehran (Iran, Islamic Republic of)

    2011-02-15

    The observed features in the temporal response patterns of a temperature-modulated chemoresistive gas sensor were used for gas diagnosis. The patterns were recorded for clean air and air contaminated with different levels of some volatile organic compounds while a staircase heating voltage waveform had been applied to the microheater of a tin oxide gas sensor that modulated its operating temperature. Combining the steady-state and transient parameters of the recorded responses in the 50-400 deg. C range resulted in discriminatory feature vectors which were utilized for contaminant classification. The information content of these feature vectors was proved sufficient for discrimination of methanol, ethanol, 1-butanol, and acetone contaminations in a wide concentration range.

  20. Utilizing the response patterns of a temperature modulated chemoresistive gas sensor for gas diagnosis

    International Nuclear Information System (INIS)

    Amini, Amir; Ghafarinia, Vahid

    2011-01-01

    The observed features in the temporal response patterns of a temperature-modulated chemoresistive gas sensor were used for gas diagnosis. The patterns were recorded for clean air and air contaminated with different levels of some volatile organic compounds while a staircase heating voltage waveform had been applied to the microheater of a tin oxide gas sensor that modulated its operating temperature. Combining the steady-state and transient parameters of the recorded responses in the 50-400 deg. C range resulted in discriminatory feature vectors which were utilized for contaminant classification. The information content of these feature vectors was proved sufficient for discrimination of methanol, ethanol, 1-butanol, and acetone contaminations in a wide concentration range.

  1. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance

    DEFF Research Database (Denmark)

    Alvero, Ayesha B; Chen, Rui; Fu, Han-Hsuan

    2009-01-01

    A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk...... to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique...... of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence...

  2. Novel Inhibitors of Cyclin-Dependent Kinases Combat Hepatocellular Carcinoma without Inducing Chemoresistance

    Czech Academy of Sciences Publication Activity Database

    Haider, C.; Grubinger, M.; Řezníčková, Eva; Weiss, T.S.; Rotheneder, H.; Miklos, W.; Berger, W.; Jorda, Radek; Zatloukal, M.; Gucký, T.; Strnad, Miroslav; Kryštof, Vladimír; Mikulits, W.

    2013-01-01

    Roč. 12, č. 10 (2013), s. 1947-1957 ISSN 1535-7163 R&D Projects: GA ČR GAP305/12/0783; GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : PRIMARY HUMAN HEPATOCYTES * SELICICLIB R-ROSCOVITINE * CELL-CYCLE Subject RIV: CE - Biochemistry Impact factor: 6.107, year: 2013

  3. Inorganic carbon acquisition in potentially toxic and non-toxic diatoms: the effect of pH-induced changes in the seawater carbonate chemistry

    DEFF Research Database (Denmark)

    Trimborn, S; Lundholm, Nina; Thoms, S

    2008-01-01

    . In terms of carbon source, all species took up both CO2 and HCO3-. K-1/2 values for inorganic carbon uptake decreased with increasing pH in two species, while in N. navis-varingica apparent affinities did not change. While the contribution of HCO3- to net fixation was more than 85% in S. stellaris......The effects of pH-induced changes in seawater carbonate chemistry on inorganic carbon (C-i) acquisition and domoic acid (DA) production were studied in two potentially toxic diatom species, Pseudo-nitzschia multiseries and Nitzschia navis-varingica, and the non-toxic Stellarima stellaris. In vivo...... activities of carbonic anhydrase (CA), photosynthetic O-2 evolution and CO2 and HCO3- uptake rates were measured by membrane inlet MS in cells acclimated to low (7.9) and high pH (8.4 or 8.9). Species-specific differences in the mode of carbon acquisition were found. While extracellular carbonic anhydrase (e...

  4. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAS

    Science.gov (United States)

    2016-04-01

    chemoresistant cancer cells can sensitize chemoresistant ovarian tumors to cisplatin treatment and inhibit ovarian cancer dissemination in a pre...determine the mechanism by which miR-181a was regulating the emergence of these CICs. What opportunities for training and professional development has...also perform data analysis to correlate those miRNAs expression with patient response to cisplatin and other clinicopathological parameters. She

  5. The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-11-01

    Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

    Science.gov (United States)

    Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

    2015-11-01

    Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

  7. [Importance of a regional observatory of malarial chemoresistance, an emerging public health problem in the Guyanas region].

    Science.gov (United States)

    Esterre, P; Volney, B; Meynard, J-B; Legrand, E

    2009-08-01

    A regular implementation of prophylactic and therapeutic decision trees was organized on a consensus basis in Cayenne, French Guiana in 1990, 1995 and 2002. The updated recommendations were based on the knowledge of the in vitro chemosensitivity profiles of the local isolates, mainly coming from big rivers (Maroni and Oyapock, frontiers with Suriname and Brazil, respectively; and more recently Approuague). Most of the patients infected by Plasmodium falciparum were followed by the medical staff of the main hospitals (Cayenne and Saint-Laurent) and of the peripheral health centers in remote areas. Consequently the epidemiological situation and evolution of chemoresistance have been widely observed on a long-term (since 1994) basis in the Maroni region. Yet, we have only partial information coming from the Oyapock valley, even though an important (most of the time) illegal immigration has been developing since the 90s' leading to a notable modification of the epidemiological status of malaria in this eastern region, including a regular increase of P. vivax infections. Presently very little P. vivax chloroquine (and mefloquine) resistance has been identified but this result could lead to a real public health problem in a near future. As such, the National Reference Center on Plasmodium Chemoresistance in the French West Indies and Guiana (CNRCP-AG in French) is a unique observatory of malaria chemoresistance in the Guyanese shield which works with research laboratories of the Institut Pasteur, Paris. This network strategy offers a very attractive perspective for applications of modern tools, including the validation of chemoresistance molecular markers, for malaria control at both medical and public health levels. Some examples related to chloroquine and artemether resistance are given.

  8. Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G

    2001-01-01

    The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.

  9. Mergers + acquisitions.

    Science.gov (United States)

    Hoppszallern, Suzanna

    2002-05-01

    The hospital sector in 2001 led the health care field in mergers and acquisitions. Most deals involved a network augmenting its presence within a specific region or in a market adjacent to its primary service area. Analysts expect M&A activity to increase in 2002.

  10. [A novel chemo-resistant gene MSX2 discovered by establishment of two pancreatic cancer drug resistant cell lines JF305/CDDP and PANC-1/GEM].

    Science.gov (United States)

    Yuan, W; Sui, C G; Ma, X; Ma, J

    2018-05-23

    Objective: To explore new multidrug resistant genes of pancreatic cancer by establishment and characterization of chemo-resistant cell lines. Methods: The cisplatin-resistant cell line JF305/CDDP and the gemcitabine-resistant cell line PANC-1/GEM were induced by high-dose intermittent treatment. CCK-8 assay was used to detect the 50% inhibiting concentration (IC(50)), drug resistance index (R), cross-resistance, and growth difference of different cells. The changes of cell cycle and migration ability of drug-resistant cells were determined by flow cytometry and transwell assay, respectively. And then real-time fluorescence quantitative PCR was used to detect the expression of multidrug resistance-related genes. Results: The drug resistance indexes of JF305/CDDP and PANC-1/GEM were 15.3 and 27.31, respectively, and there was cross-resistance. Compared with the parental cells, the proliferation rate of JF305/CDDP was decreased by 40% on the fourth day ( P PANC-1 cells upregulated MRP2 level ( P PANC-1/GEM, were successfully established. MSX2 might be a new drug resistance related gene in pancreatic cancer cells by up-regulation of MRP2 expression.

  11. Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy

    Directory of Open Access Journals (Sweden)

    Marcin P Komorowski

    2016-01-01

    Full Text Available Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. The infected cultures were more sensitive to doxorubicin-mediated killing both in vitro and in tumor-challenged mice. Mechanistically, the combination treatment increased apoptosis and phagocytosis of tumor material by dendritic cells associated with induction of antitumor immunity. Targeting syngeneic tumors with this regimen increased intratumoral infiltration of antitumor CD8+ T cells. This was further enhanced by reducing the immunosuppressive network by the virally-delivered CXCR4 antagonist, which augmented antitumor immune responses and led to tumor-free survival. Our results define novel strategies for treatment of drug-resistant ovarian cancer that increase immunogenic cell death and reverse the immunosuppressive tumor microenvironment, culminating in antitumor immune responses that control metastatic tumor growth.

  12. Chemoresistance, Cancer Stem Cells, and miRNA Influences: The Case for Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Alfred Buhagiar

    2015-01-01

    Full Text Available Neuroblastoma is a type of cancer that develops most often in infants and children under the age of five years. Neuroblastoma originates within the peripheral sympathetic ganglia, with 30% of the cases developing within the adrenal medulla, although it can also occur within other regions of the body such as nerve tissue in the spinal cord, neck, chest, abdomen, and pelvis. MicroRNAs (miRNAs regulate cellular pathways, differentiation, apoptosis, and stem cell maintenance. Such miRNAs regulate genes involved in cellular processes. Consequently, they are implicated in the regulation of a spectrum of signaling pathways within the cell. In essence, the role of miRNAs in the development of cancer is of utmost importance for the understanding of dysfunctional cellular pathways that lead to the conversion of normal cells into cancer cells. This review focuses on highlighting the recent, important implications of miRNAs within the context of neuroblastoma basic research efforts, particularly concerning miRNA influences on cancer stem cell pathology and chemoresistance pathology for this condition, together with development of translational medicine approaches for novel diagnostic tools and therapies for this neuroblastoma.

  13. Synthesis of Nanodiamond-Daunorubicin Conjugates to Overcome Multidrug Chemoresistance in Leukemia

    Science.gov (United States)

    Man, Han B.; Kim, Hansung; Kim, Ho-Joong; Robinson, Erik; Liu, Wing Kam; Chow, Edward Kai-Hua; Ho, Dean

    2013-01-01

    Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains. PMID:23916889

  14. Hepatic stellate cells secreted hepatocyte growth factor contributes to the chemoresistance of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guofeng Yu

    Full Text Available As the main source of extracellular matrix proteins in tumor stroma, hepatic stellate cells (HSCs have a great impact on biological behaviors of hepatocellular carcinoma (HCC. In the present study, we have investigated a mechanism whereby HSCs modulate the chemoresistance of hepatoma cells. We used human HSC line lx-2 and chemotherapeutic agent cisplatin to investigate their effects on human HCC cell line Hep3B. The results showed that cisplatin resistance in Hep3B cells was enhanced with LX-2 CM (cultured medium exposure in vitro as well as co-injection with LX-2 cells in null mice. Meanwhile, in presence of LX-2 CM, Hep3B cells underwent epithelial to mesenchymal transition (EMT and upregulation of cancer stem cell (CSC -like properties. Besides, LX-2 cells synthesized and secreted hepatic growth factor (HGF into the CM. HGF receptor tyrosine kinase mesenchymal-epithelial transition factor (Met was activated in Hep3B cells after LX-2 CM exposure. The HGF level of LX-2 CM could be effectively reduced by using HGF neutralizing antibody. Furthermore, depletion of HGF in LX-2 CM abolished its effects on activation of Met as well as promotion of the EMT, CSC-like features and cisplatin resistance in Hep3B cells. Collectively, secreting HGF into tumor milieu, HSCs may decrease hepatoma cells sensitization to chemotherapeutic agents by promoting EMT and CSC-like features via HGF/Met signaling.

  15. Mergers & Acquisitions

    DEFF Research Database (Denmark)

    Fomcenco, Alex

    This dissertation is a legal dogmatic thesis, the goal of which is to describe and analyze the current state of law in Europe in regard to some relevant selected elements related to mergers and acquisitions, and the adviser’s counsel in this regard. Having regard to the topic of the dissertation...... and fiscal neutrality, group-related issues, holding-structure issues, employees, stock exchange listing issues, and corporate nationality....

  16. MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

    Directory of Open Access Journals (Sweden)

    Zi-Xun Yan

    2015-01-01

    Full Text Available MicroRNAs (miRs play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32, T-cell lymphoblastic lymphoma (n=16, peripheral T-cell lymphoma, not otherwise specified (n=45, anaplastic large cell lymphoma (n=15, and angioimmunoblastic T-cell lymphoma (n=22. Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

  17. Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

    Science.gov (United States)

    Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

    2017-06-01

    Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

  18. Schizophrenia and second language acquisition.

    Science.gov (United States)

    Bersudsky, Yuly; Fine, Jonathan; Gorjaltsan, Igor; Chen, Osnat; Walters, Joel

    2005-05-01

    Language acquisition involves brain processes that can be affected by lesions or dysfunctions in several brain systems and second language acquisition may depend on different brain substrates than first language acquisition in childhood. A total of 16 Russian immigrants to Israel, 8 diagnosed schizophrenics and 8 healthy immigrants, were compared. The primary data for this study were collected via sociolinguistic interviews. The two groups use language and learn language in very much the same way. Only exophoric reference and blocking revealed meaningful differences between the schizophrenics and healthy counterparts. This does not mean of course that schizophrenia does not induce language abnormalities. Our study focuses on those aspects of language that are typically difficult to acquire in second language acquisition. Despite the cognitive compromises in schizophrenia and the manifest atypicalities in language of speakers with schizophrenia, the process of acquiring a second language seems relatively unaffected by schizophrenia.

  19. Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

    DEFF Research Database (Denmark)

    Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

    2012-01-01

    Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

  20. 2017 NAIP Acquisition Map

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — Planned States for 2017 NAIP acquisition and acquisition status layer (updated daily). Updates to the acquisition seasons may be made during the season to...

  1. Syntax acquisition.

    Science.gov (United States)

    Crain, Stephen; Thornton, Rosalind

    2012-03-01

    Every normal child acquires a language in just a few years. By 3- or 4-years-old, children have effectively become adults in their abilities to produce and understand endlessly many sentences in a variety of conversational contexts. There are two alternative accounts of the course of children's language development. These different perspectives can be traced back to the nature versus nurture debate about how knowledge is acquired in any cognitive domain. One perspective dates back to Plato's dialog 'The Meno'. In this dialog, the protagonist, Socrates, demonstrates to Meno, an aristocrat in Ancient Greece, that a young slave knows more about geometry than he could have learned from experience. By extension, Plato's Problem refers to any gap between experience and knowledge. How children fill in the gap in the case of language continues to be the subject of much controversy in cognitive science. Any model of language acquisition must address three factors, inter alia: 1. The knowledge children accrue; 2. The input children receive (often called the primary linguistic data); 3. The nonlinguistic capacities of children to form and test generalizations based on the input. According to the famous linguist Noam Chomsky, the main task of linguistics is to explain how children bridge the gap-Chomsky calls it a 'chasm'-between what they come to know about language, and what they could have learned from experience, even given optimistic assumptions about their cognitive abilities. Proponents of the alternative 'nurture' approach accuse nativists like Chomsky of overestimating the complexity of what children learn, underestimating the data children have to work with, and manifesting undue pessimism about children's abilities to extract information based on the input. The modern 'nurture' approach is often referred to as the usage-based account. We discuss the usage-based account first, and then the nativist account. After that, we report and discuss the findings of several

  2. Concept Acquisition and Experiential Change

    Directory of Open Access Journals (Sweden)

    William S. Robinson

    2014-12-01

    Full Text Available Many have held the Acquisition of Concepts Thesis (ACT that concept acquisition can change perceptual experience. This paper explains the close relation of ACT to ADT, the thesis that acquisition of dispositions to quickly and reliably recognize a kind of thing can change perceptual experience. It then states a highly developed argument given by Siegel (2010 which, if successful, would offer strong support for ADT and indirect support for ACT. Examination of this argument, however, reveals difficulties that undermine its promise. Distinctions made in this examination help to clarify an alternative view that denies ADT and ACT while accepting that long exposure to a class of materials may induce changes in phenomenology that lie outside perceptual experience itself.

  3. Regulation of apoptosis-inducing factor-mediated, cisplatin-induced apoptosis by Akt

    OpenAIRE

    Yang, X; Fraser, M; Abedini, M R; Bai, T; Tsang, B K

    2008-01-01

    Cisplatin is a first-line chemotherapeutic for ovarian cancer, although chemoresistance limits treatment success. Apoptosis, an important determinant of cisplatin sensitivity, occurs via caspase-dependent and -independent mechanisms. Activation of the protein kinase Akt, commonly observed in ovarian tumours, confers resistance to ovarian cancer cells via inhibition of caspase-dependent apoptosis. However, the effect of Akt on cisplatin-induced, caspase-independent apoptosis remains unclear. W...

  4. Exploring the potential of acquisition curves of the anhysteretic remanent magnetization as a tool to detect subtle magnetic alteration induced by heating

    Science.gov (United States)

    de Groot, Lennart V.; Dekkers, Mark J.; Mullender, Tom A. T.

    2012-03-01

    Recently, many new methods and improved protocols to determine the absolute paleointensity of lavas reliably have been proposed. Here we study eight recent flows from three different volcanic edifices (Mt. Etna, La Palma and Hawaii) with the so-called multispecimen parallel differential pTRM (MSP) method including the recently proposed domain-state correction (MSP-DSC) (Fabian and Leonhardt, 2010). Surprisingly, apart from approximately correct paleointensity values, we observe major underestimates of the paleofield. These deviations are possibly related to alteration that is not revealed by rock-magnetic analysis. We explore the potential of high-resolution acquisition curves of the anhysteretic remanent magnetization (ARM) to detect subtle alteration in the samples. It appears that assessing changes in the ARM acquisition properties before and after heating to the desired MSP temperature discriminates between underestimates and approximately correct estimations of the paleofield in the outcomes of the MSP-DSC protocol. By combining observations from the domain-state corrected MSP protocol and ARM acquisition experiments before and after heating, an extended MSP protocol is suggested which makes it possible to assess the best set temperature for the MSP-DSC protocol and to label MSP results as being approximately correct, or an underestimate of the paleofield.

  5. Speed in Acquisitions

    DEFF Research Database (Denmark)

    Meglio, Olimpia; King, David R.; Risberg, Annette

    2017-01-01

    The advantage of speed is often invoked by academics and practitioners as an essential condition during post-acquisition integration, frequently without consideration of the impact earlier decisions have on acquisition speed. In this article, we examine the role speed plays in acquisitions across...... the acquisition process using research organized around characteristics that display complexity with respect to acquisition speed. We incorporate existing research with a process perspective of acquisitions in order to present trade-offs, and consider the influence of both stakeholders and the pre......-deal-completion context on acquisition speed, as well as the organization’s capabilities to facilitating that speed. Observed trade-offs suggest both that acquisition speed often requires longer planning time before an acquisition and that associated decisions require managerial judgement. A framework for improving...

  6. Language Acquisition without an Acquisition Device

    Science.gov (United States)

    O'Grady, William

    2012-01-01

    Most explanatory work on first and second language learning assumes the primacy of the acquisition phenomenon itself, and a good deal of work has been devoted to the search for an "acquisition device" that is specific to humans, and perhaps even to language. I will consider the possibility that this strategy is misguided and that language…

  7. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    Full Text Available Abstract Background The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Methods Thirty-four companion animals (27 dogs and 7 cats were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. Results The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6% the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17% experienced short lived partial responses (1-3 months duration while all the others died of progressive disease within two months. Conclusions high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of

  8. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Baldi, Alfonso; Buglioni, Sabrina; Carocci, Francesca; de Bazzichini, Giulia Milesi; Betti, Gianluca; Pantaleo, Ilaria; Menicagli, Francesco; Citro, Gennaro; Fais, Stefano

    2011-12-28

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in

  9. Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state

    Directory of Open Access Journals (Sweden)

    Ahmed El-Badawy

    2017-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs. Methods The effect of soluble factors secreted from MCF7, Hela, and HepG2 cancer cell lines on BM-MSCs was assessed using a Transwell indirect coculture system. After 5 days of coculture, BM-MSCs were characterized by flow cytometry for surface marker expression, by qPCR for gene expression profile, and by confocal immunofluorescence for marker expression. We then measured the sensitivity of cocultured BM-MSCs to chemotherapeutic agents, their cell cycle profile, and their response to DNA damage. The sphere formation, invasive properties, and in-vivo performance of BM-MSCs after coculture with cancer cells were also measured. Results Indirect coculture of cancer cells and BM-MSCs, without direct cell contact, generated slow cycling, chemoresistant spheroid stem cells that highly expressed markers of pluripotency, cancer cells, and cancer stem cells (CSCs. They also displayed properties of a side population and enhanced sphere formation in culture. Accordingly, these cells were termed cancer-induced stem cells (CiSCs. CiSCs showed a more mesenchymal phenotype that was further augmented upon TGF-β stimulation and demonstrated a high expression of the β-catenin pathway and ALDH1A1. Conclusions These findings demonstrate that MSCs, recruited to the tumor microenvironment in large numbers, may display cellular plasticity, acquire a more stem-like state, and acquire some properties of CSCs upon

  10. Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.

    Science.gov (United States)

    Niu, Yuchun; Ma, Feng; Huang, Weimei; Fang, Shun; Li, Man; Wei, Ting; Guo, Linlang

    2017-01-09

    Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer. We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC. Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.

  11. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle

    2006-01-01

    for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value...... for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels...

  12. APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

    International Nuclear Information System (INIS)

    Petty, Russell D; Wang, Weiguang; Gilbert, Fiona; Semple, Scot; Collie-Duguid, Elaina SR; Samuel, Leslie M; Murray, Graeme I; MacDonald, Graham; O'Kelly, Terrence; Loudon, Malcolm; Binnie, Norman; Aly, Emad; McKinlay, Aileen

    2009-01-01

    5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets. Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified. APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set

  13. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  14. Modelling live forensic acquisition

    CSIR Research Space (South Africa)

    Grobler, MM

    2009-06-01

    Full Text Available This paper discusses the development of a South African model for Live Forensic Acquisition - Liforac. The Liforac model is a comprehensive model that presents a range of aspects related to Live Forensic Acquisition. The model provides forensic...

  15. Playing at Serial Acquisitions

    NARCIS (Netherlands)

    J.T.J. Smit (Han); T. Moraitis (Thras)

    2010-01-01

    textabstractBehavioral biases can result in suboptimal acquisition decisions-with the potential for errors exacerbated in consolidating industries, where consolidators design serial acquisition strategies and fight escalating takeover battles for platform companies that may determine their future

  16. Mergers and Acquisitions

    OpenAIRE

    Frasch, Manfred; Leptin, Maria

    2000-01-01

    Mergers and acquisitions (M&As) are booming a strategy of choice for organizations attempting to maintain a competitive advantage. Previous research on mergers and acquisitions declares that acquirers do not normally benefit from acquisitions. Targets, on the other hand, have a tendency of gaining positive returns in the few days surrounding merger announcements due to several characteristic on the acquisitions deal. The announcement period wealth effect on acquiring firms, however, is as cle...

  17. Effects of magnesium sulfate on the acquisition and reinstatement of ...

    African Journals Online (AJOL)

    In the current study, the effects of magnesium sulfate on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in an animal model were investigated. The acquisition and extinction and reinstatement phases induced using morphine 40 and 10mg/kg. Magnesium sulfate 300 and 600 ...

  18. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    International Nuclear Information System (INIS)

    Pang, Lisa Y.; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J.

    2011-01-01

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology

  19. Canine Mammary Cancer Stem Cells are Radio- and Chemo-Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Lisa Y., E-mail: lisa.pang@ed.ac.uk; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. [Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG (United Kingdom)

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  20. Smart acquisition EELS

    International Nuclear Information System (INIS)

    Sader, Kasim; Schaffer, Bernhard; Vaughan, Gareth; Brydson, Rik; Brown, Andy; Bleloch, Andrew

    2010-01-01

    We have developed a novel acquisition methodology for the recording of electron energy loss spectra (EELS) using a scanning transmission electron microscope (STEM): 'Smart Acquisition'. Smart Acquisition allows the independent control of probe scanning procedures and the simultaneous acquisition of analytical signals such as EELS. The original motivation for this work arose from the need to control the electron dose experienced by beam-sensitive specimens whilst maintaining a sufficiently high signal-to-noise ratio in the EEL signal for the extraction of useful analytical information (such as energy loss near edge spectral features) from relatively undamaged areas. We have developed a flexible acquisition framework which separates beam position data input, beam positioning, and EELS acquisition. In this paper we demonstrate the effectiveness of this technique on beam-sensitive thin films of amorphous aluminium trifluoride. Smart Acquisition has been used to expose lines to the electron beam, followed by analysis of the structures created by line-integrating EELS acquisitions, and the results are compared to those derived from a standard EELS linescan. High angle annular dark-field images show clear reductions in damage for the Smart Acquisition areas compared to the conventional linescan, and the Smart Acquisition low loss EEL spectra are more representative of the undamaged material than those derived using a conventional linescan. Atomically resolved EELS of all four elements of CaNdTiO show the high resolution capabilities of Smart Acquisition.

  1. Smart acquisition EELS

    Energy Technology Data Exchange (ETDEWEB)

    Sader, Kasim, E-mail: k.sader@leeds.ac.uk [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Schaffer, Bernhard [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Department of Physics and Astronomy, University of Glasgow (United Kingdom); Vaughan, Gareth [Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Brydson, Rik [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Brown, Andy [Institute for Materials Research, University of Leeds, LS2 9JT (United Kingdom); Bleloch, Andrew [SuperSTEM, J block, Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Department of Engineering, University of Liverpool, Liverpool (United Kingdom)

    2010-07-15

    We have developed a novel acquisition methodology for the recording of electron energy loss spectra (EELS) using a scanning transmission electron microscope (STEM): 'Smart Acquisition'. Smart Acquisition allows the independent control of probe scanning procedures and the simultaneous acquisition of analytical signals such as EELS. The original motivation for this work arose from the need to control the electron dose experienced by beam-sensitive specimens whilst maintaining a sufficiently high signal-to-noise ratio in the EEL signal for the extraction of useful analytical information (such as energy loss near edge spectral features) from relatively undamaged areas. We have developed a flexible acquisition framework which separates beam position data input, beam positioning, and EELS acquisition. In this paper we demonstrate the effectiveness of this technique on beam-sensitive thin films of amorphous aluminium trifluoride. Smart Acquisition has been used to expose lines to the electron beam, followed by analysis of the structures created by line-integrating EELS acquisitions, and the results are compared to those derived from a standard EELS linescan. High angle annular dark-field images show clear reductions in damage for the Smart Acquisition areas compared to the conventional linescan, and the Smart Acquisition low loss EEL spectra are more representative of the undamaged material than those derived using a conventional linescan. Atomically resolved EELS of all four elements of CaNdTiO show the high resolution capabilities of Smart Acquisition.

  2. Roles of the Nucleus Accumbens (Shell in the Acquisition and Expression of Morphine-Induced Conditioned Behavior in Freely Moving Rats

    Directory of Open Access Journals (Sweden)

    Sara Karimi

    2014-01-01

    Conclusions: Since stimulation of dopaminergic neurons increases tendency to dependence to morphine, therefore in the present study, the stimulation of the NAc suppressed morphine-induced CPP that this shows impairment of learning and memory formation.

  3. SMV1 virus-induced CRISPR spacer acquisition from the conjugative plasmid pMGB1 in Sulfolobus solfataricus P2

    DEFF Research Database (Denmark)

    Erdmann, Susanne; Shah, Shiraz Ali; Garrett, Roger Antony

    2013-01-01

    Organisms of the crenarchaeal order Sulfolobales carry complex CRISPR (clustered regularly interspaced short palindromic repeats) adaptive immune systems. These systems are modular and show extensive structural and functional diversity, especially in their interference complexes. The primary...... targets are an exceptional range of diverse viruses, many of which propagate stably within cells and follow lytic life cycles without producing cell lysis. These properties are consistent with the difficulty of activating CRISPR spacer uptake in the laboratory, but appear to conflict with the high...... complexity and diversity of the CRISPR immune systems that are found among the Sulfolobales. In the present article, we re-examine the first successful induction of archaeal spacer acquisition in our laboratory that occurred exclusively for the conjugative plasmid pMGB1 in Sulfolobus solfataricus P2...

  4. Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells.

    Science.gov (United States)

    Liu, Yanjun; DU, Fangfang; Zhao, Qiannan; Jin, Jian; Ma, Xin; Li, Huazhong

    2015-06-01

    Colon cancer has a high incidence in individuals >60-years-old. The commonly used chemotherapeutic agent, 5-fluorouracil (5-FU), has gradually lost its potency in treating colorectal cancer following the acquisition of resistance. Drug resistance is usually associated with epithelial-mesenchymal transitions (EMTs) in cancer cells. In the present study, the EMT phenotypes of two colon cancer cell lines, wild-type (HCT-8/WT) and 5-FU-resistant (HCT-8/5-FU), were characterized following the analysis of cellular migration, proliferation, morphology and molecular changes. In order to further clarify the mechanism of EMT in HCT-8/5-FU cells, the effect of EMT pathway inhibitors upon drug sensitivity was investigated. The results revealed that the Hedgehog signaling pathway inhibitor, GDC0449, reversed drug resistance. Therefore, inhibition of the Hedgehog pathway may provide a novel chemotherapeutic strategy for the treatment of patients with 5-FU-resistant colon cancer.

  5. Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Su

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.

  6. Upregulation of autophagy-related gene-5 (ATG-5 is associated with chemoresistance in human gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jie Ge

    Full Text Available Autophagy-related gene-5 (ATG-5 is one of the key regulators of autophagic cell death. It has been widely regarded as a protective molecular mechanism for tumor cells during the course of chemotherapy. In the present study, we investigated the expression pattern of ATG-5 and multidrug resistance-associated protein-1 (MRP-1 in 135 gastric cancers (GC patients who were treated with epirubicin, cisplatin and 5-FU adjuvant chemotherapy (ECF following surgical resection and explored their potential clinical significance. We found that both ATG-5 (77.78% and MRP-1 (79.26% were highly expressed in GC patients. ATG-5 expression was significantly associated with depth of wall invasion, TNM stages and distant metastasis of GC (P<0.05, whereas MRP-1 expression was significantly linked with tumor size, depth of wall invasion, lymph node metastasis, TNM stages and differentiation status (P<0.05. ATG-5 expression was positively correlated with MRP-1 (rp = 0.616, P<0.01. Increased expression of ATG-5 and MPR-1 was significantly correlated with poor overall survival (OS; P<0.01 and disease free survival (DFS; P<0.01 of our GC cohort. Furthermore, we demonstrated that ATG-5 was involved in drug resistant of GC cells, which was mainly through regulating autophagy. Our data suggest that upregulated expression of ATG-5, an important molecular feature of protective autophagy, is associated with chemoresistance in GC. Expression of ATG-5 and MRP-1 may be independent prognostic markers for GC treatment.

  7. Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Ardian Latifi

    Full Text Available Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD and non-adherent (NAD cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN and 14 chemoresistant (CR. AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125, epithelial cell adhesion molecule (EpCAM and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p. injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.

  8. Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

    2016-12-06

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

  9. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chandan Kanta Das

    2018-03-01

    Full Text Available Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC, and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6 of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549rDOX20 and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468r5-FU2000 cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549rDOX20 and MDA-MB-468r5-FU2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer.

  10. ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Khuder Sadik A

    2005-05-01

    Full Text Available Abstract Background Although 40–50% of non-small cell lung cancer (NSCLC tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1 were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated. Results Following validation, single variable models best correlated with chemoresistance (p ERCC2/XPC, ABCC5/GTF2H2, ERCC2/GTF2H2, XPA/XPC and XRCC1/XPC. All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was (ABCC5/GTF2H2, ERCC2/GTF2H2 with an R2 value of 0.96 (p Conclusion These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.

  11. Melatonin Protects Human Cells from Clustered DNA Damages, Killing and Acquisition of Soft Agar Growth Induced by X-rays or 970 MeV/n Fe ions

    Energy Technology Data Exchange (ETDEWEB)

    Das, B.; Sutherland, B.; Bennett, P. V.; Cutter, N. C.; Sutherland, J. C.

    2011-06-01

    We tested the ability of melatonin (N-acetyl-5 methoxytryptamine), a highly effective radical scavenger and human hormone, to protect DNA in solution and in human cells against induction of complex DNA clusters and biological damage induced by low or high linear energy transfer radiation (100 kVp X-rays, 970 MeV/nucleon Fe ions). Plasmid DNA in solution was treated with increasing concentrations of melatonin (0.0-3.5 mM) and were irradiated with X-rays. Human cells (28SC monocytes) were also irradiated with X-rays and Fe ions with and without 2 mM melatonin. Agarose plugs containing genomic DNA were subjected to Contour Clamped Homogeneous Electrophoretic Field (CHEF) followed by imaging and clustered DNA damages were measured by using Number Average length analysis. Transformation experiments on human primary fibroblast cells using soft agar colony assay were carried out which were irradiated with Fe ions with or without 2 mM melatonin. In plasmid DNA in solution, melatonin reduced the induction of single- and double-strand breaks. Pretreatment of human 28SC cells for 24 h before irradiation with 2 mM melatonin reduced the level of X-ray induced double-strand breaks by {approx}50%, of abasic clustered damages about 40%, and of Fe ion-induced double-strand breaks (41% reduction) and abasic clusters (34% reduction). It decreased transformation to soft agar growth of human primary cells by a factor of 10, but reduced killing by Fe ions only by 20-40%. Melatonin's effective reduction of radiation-induced critical DNA damages, cell killing, and striking decrease of transformation suggest that it is an excellent candidate as a countermeasure against radiation exposure, including radiation exposure to astronaut crews in space travel.

  12. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yongsheng, E-mail: yongshengtanwhu@126.com; Li, Yan, E-mail: liyansd2@163.com

    2015-10-23

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 {sup low} and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96{sup ®}Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 {sup low}, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases

  13. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    International Nuclear Information System (INIS)

    Tan, Yongsheng; Li, Yan

    2015-01-01

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 "l"o"w and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96"®Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 "l"o"w, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases expression of NR4A1

  14. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells.

    Science.gov (United States)

    Das, Chandan Kanta; Linder, Benedikt; Bonn, Florian; Rothweiler, Florian; Dikic, Ivan; Michaelis, Martin; Cinatl, Jindrich; Mandal, Mahitosh; Kögel, Donat

    2018-03-01

    Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549 r DOX 20 ) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468 r 5-FU 2000 ) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549 r DOX 20 and MDA-MB-468 r 5-FU 2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Acquisition Research Program Homepage

    OpenAIRE

    2015-01-01

    Includes an image of the main page on this date and compressed file containing additional web pages. Established in 2003, Naval Postgraduate School’s (NPS) Acquisition Research Program provides leadership in innovation, creative problem solving and an ongoing dialogue, contributing to the evolution of Department of Defense acquisition strategies.

  16. Making Acquisition Measurable

    Science.gov (United States)

    2011-04-30

    Corporation. All rights reserved End Users Administrator/ Maintainer (A/M) Subject Matter Expert ( SME ) Trainer/ Instructor Manager, Evaluator, Supervisor... CMMI ) - Acquisition (AQ) © 2011 The MITRE Corporation. All rights reserved 13 CMMI -Development Incremental iterative development (planning & execution...objectives Constructing games highlighting particular aspects of proposed CCOD® acquisition, and conducting exercises with Subject Matter Experts ( SMEs

  17. KIF14 Promotes AKT Phosphorylation and Contributes to Chemoresistance in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stina M. Singel

    2014-03-01

    Full Text Available Despite evidence that kinesin family member 14 (KIF14 can serve as a prognostic biomarker in various solid tumors, how it contributes to tumorigenesis remains unclear. We observed that experimental decrease in KIF14 expression increases docetaxel chemosensitivity in estrogen receptor–negative/progesterone receptor–negative/human epidermal growth factor receptor 2-negative, “triple-negative” breast cancers (TNBC. To investigate the oncogenic role of KIF14, we used noncancerous human mammary epithelial cells and ectopically expressed KIF14 and found increased proliferative capacity, increased anchorage-independent grown in vitro, and increased resistance to docetaxel but not to doxorubicin, carboplatin, or gemcitabine. Seventeen benign breast biopsies of BRCA1 or BRCA2 mutation carriers showed increased KIF14 mRNA expression by fluorescence in situ hybridization compared to controls with no known mutations in BRCA1 or BRCA2, suggesting increased KIF14 expression as a biomarker of high-risk breast tissue. Evaluation of 34 cases of locally advanced TNBC showed that KIF14 expression significantly correlates with chemotherapy-resistant breast cancer. KIF14 knockdown also correlates with decreased AKT phosphorylation and activity. Live-cell imaging confirmed an insulin-induced temporal colocalization of KIF14 and AKT at the plasma membrane, suggesting a potential role of KIF14 in promoting activation of AKT. An experimental small-molecule inhibitor of KIF14 was then used to evaluate the potential anticancer benefits of downregulating KIF14 activity. Inhibition of KIF14 shows a chemosensitizing effect and correlates with decreasing activation of AKT. Together, these findings show an early and critical role for KIF14 in the tumorigenic potential of TNBC, and therapeutic targeting of KIF14 is feasible and effective for TNBC.

  18. Mergers and Acquisitions

    DEFF Research Database (Denmark)

    Risberg, Annette

    Introduction to the study of mergers and acquisitions. This book provides an understanding of the mergers and acquisitions process, how and why they occur, and also the broader implications for organizations. It presents issues including motives and planning, partner selection, integration......, employee experiences and communication. Mergers and acquisitions remain one of the most common forms of growth, yet they present considerable challenges for the companies and management involved. The effects on stakeholders, including shareholders, managers and employees, must be considered as well...... by editorial commentaries and reflects the important organizational and behavioural aspects which have often been ignored in the past. By providing this in-depth understanding of the mergers and acquisitions process, the reader understands not only how and why mergers and acquisitions occur, but also...

  19. Data Acquisition System

    International Nuclear Information System (INIS)

    Cirstea, C.D.; Buda, S.I.; Constantin, F.

    2005-01-01

    This paper deals with a multi parametric acquisition system developed for a four input Analog to Digital Converter working in CAMAC Standard. The acquisition software is built in MS Visual C++ on a standard PC with a USB interface. It has a visual interface which permits Start/Stop of the acquisition, setting the type of acquisition (True/Live time), the time and various menus for primary data acquisition. The spectrum is dynamically visualized with a moving cursor indicating the content and position. The microcontroller PIC16C765 is used for data transfer from ADC to PC; The microcontroller and the software create an embedded system which emulates the CAMAC protocol programming the 4 input ADC for operating modes ('zero suppression', 'addressed' and 'sequential') and handling the data transfers from ADC to its internal memory. From its memory the data is transferred into the PC by the USB interface. The work is in progress. (authors)

  20. Data acquisition system

    International Nuclear Information System (INIS)

    Cirstea, D.C.; Buda, S.I.; Constantin, F.

    2005-01-01

    The topic of this paper deals with a multi parametric acquisition system developed around a four input Analog to Digital Converter working in CAMAC Standard. The acquisition software is built in MS Visual C++ on a standard PC with a USB interface. It has a visual interface which permits Start/Stop of the acquisition, setting the type of acquisition (True/Live time), the time and various menus for primary data acquisition. The spectrum is dynamically visualized with a moving cursor indicating the content and position. The microcontroller PIC16C765 is used for data transfer from ADC to PC; The microcontroller and the software create an embedded system which emulates the CAMAC protocol programming, the 4 input ADC for operating modes ('zero suppression', 'addressed' and 'sequential') and handling the data transfers from ADC to its internal memory. From its memory the data is transferred into the PC by the USB interface. The work is in progress. (authors)

  1. Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

    Directory of Open Access Journals (Sweden)

    Miñarro José

    2010-03-01

    Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

  2. Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73

    International Nuclear Information System (INIS)

    Thangasamy, Thilakavathy; Sittadjody, Sivanandane; Mitchell, Geoffrey C; Mendoza, Erin E; Radhakrishnan, Vijayababu M; Limesand, Kirsten H; Burd, Randy

    2010-01-01

    The alkylating agent Dacarbazine (DTIC) has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73. DB-1 melanoma (p53 wildtype), and SK Mel 28 (p53 mutant) cell lines were treated with TMZ (400 μM) for 48 hrs followed by Qct (75 μM) for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation. After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM) and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis. This study demonstrates that Qct can sensitize cells to TMZ

  3. Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Vijayababu M

    2010-06-01

    Full Text Available Abstract Background The alkylating agent Dacarbazine (DTIC has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73. Methods DB-1 melanoma (p53 wildtype, and SK Mel 28 (p53 mutant cell lines were treated with TMZ (400 μM for 48 hrs followed by Qct (75 μM for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation. Results After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis. Conclusion

  4. Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16.

    Science.gov (United States)

    Yang, Hua; Yao, Jun; Yin, Jiangpin; Wei, Xuan

    2016-05-01

    The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner. Moreover, downregulated LRIG1 in SKOV3 could enhance the colony formation and resist the inhibition of proliferation by VP16, leading to the elevated expression of Bcl-2 and decreased apoptosis of SKOV3. Interestingly, our results uncovered that the multidrug resistance-associated protein 1 (MRP-1) was upregulated for the chemoresistance of VP16. To overcome the chemoresistance of SKOV3, SKOV3/VP16 was ectopically expressed of LRIG1. We found that the inhibition of VP16 on colony formation and proliferation was remarkably enhanced with increased apoptosis in SKOV3/VP16. Furthermore, the expression of MRP-1 and Bcl-2 was also inhibited, suggesting that the LRIG1could negatively control MRP-1 and the apoptosis to improve the sensitivity of VP16-related chemotherapy.

  5. Indexing mergers and acquisitions

    OpenAIRE

    Gang, Jianhua; Guo, Jie (Michael); Hu, Nan; Li, Xi

    2017-01-01

    We measure the efficiency of mergers and acquisitions by putting forward an index (the ‘M&A Index’) based on stochastic frontier analysis. The M&A Index is calculated for each takeover deal and is standardized between 0 and 1. An acquisition with a higher index encompasses higher efficiency. We find that takeover bids with higher M&A Indices are more likely to succeed. Moreover, the M&A Index shows a strong and positive relation with the acquirers’ post-acquisition stock perfo...

  6. Acquisition Workforce Annual Report 2006

    Data.gov (United States)

    General Services Administration — This is the Federal Acquisition Institute's (FAI's) Annual demographic report on the Federal acquisition workforce, showing trends by occupational series, employment...

  7. Acquisition Workforce Annual Report 2008

    Data.gov (United States)

    General Services Administration — This is the Federal Acquisition Institute's (FAI's) Annual demographic report on the Federal acquisition workforce, showing trends by occupational series, employment...

  8. The Acquisition of Particles

    African Journals Online (AJOL)

    process of language acquisition on the basis of linguistic evidence the child is exposed to. ..... particle verbs are recognized in language processing differs from the way morphologically ..... In Natural Language and Linguistic Theory 11.

  9. High speed data acquisition

    International Nuclear Information System (INIS)

    Cooper, P.S.

    1997-07-01

    A general introduction to high speed data acquisition system techniques in modern particle physics experiments is given. Examples are drawn from the SELEX(E78 1) high statistics charmed baryon production and decay experiment now taking data at Fermilab

  10. Modified spectrophotometer for multi-dimensional circular dichroism/fluorescence data acquisition in titration experiments: application to the pH and guanidine-HCI induced unfolding of apomyoglobin.

    Science.gov (United States)

    Ramsay, G; Ionescu, R; Eftink, M R

    1995-01-01

    In a previous paper (Ramsay and Eftink, Biophys. J. 66:516-523) we reported the development of a modified spectrophotometer that can make nearly simultaneous circular dichroism (CD) and fluorescence measurements. This arrangement allows multiple data sets to be collected during a single experiment, resulting in a saving of time and material, and improved correlation between the different types of measurements. The usefulness of the instrument was shown by thermal melting experiments on several different protein systems. This CD/fluorometer spectrophotometer has been further modified by interfacing with a syringe pump and a pH meter. This arrangement allows ligand, pH, and chemical denaturation titration experiments to be performed while monitoring changes in the sample's CD, absorbance, fluorescence, and light scattering properties. Our data acquisition program also has an ability to check whether the signals have approached equilibrium before the data is recorded. For performing pH titrations we have developed a procedure which uses the signal from a pH meter in a feedback circuit in order to collect data at evenly spaced pH intervals. We demonstrate the use of this instrument with studies of the unfolding of sperm whale apomyoglobin, as induced by acid pH and by the addition of guanidine-HCI. Images FIGURE 2 PMID:8527683

  11. Overexpression of MEOX2 and TWIST1 is associated with H3K27me3 levels and determines lung cancer chemoresistance and prognosis.

    Directory of Open Access Journals (Sweden)

    Federico Ávila-Moreno

    Full Text Available Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs, but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66-51% of cases in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients.

  12. Therapeutic targeting of Neu1 sialidase with oseltamivir phosphate (Tamiflu® disables cancer cell survival in human pancreatic cancer with acquired chemoresistance

    Directory of Open Access Journals (Sweden)

    O’Shea LK

    2014-01-01

    Full Text Available Leah K O'Shea,1 Samar Abdulkhalek,1 Stephanie Allison,2 Ronald J Neufeld,2 Myron R Szewczuk11Department of Biomedical and Molecular Sciences, 2Department of Chemical Engineering, Queen's University, Kingston, ON, CanadaBackground: Resistance to drug therapy, along with high rates of metastasis, contributes to the low survival rate in patients diagnosed with pancreatic cancer. An alternate treatment for human pancreatic cancer involving targeting of Neu1 sialidase with oseltamivir phosphate (Tamiflu® was investigated in human pancreatic cancer (PANC1 cells with acquired resistance to cisplatin and gemcitabine. Its efficacy in overcoming the intrinsic resistance of the cell to chemotherapeutics and metastasis was evaluated.Methods: Microscopic imaging, immunocytochemistry, immunohistochemistry, and WST-1 cell viability assays were used to evaluate cell survival, morphologic changes, and expression levels of E-cadherin, N-cadherin, and VE-cadherin before and after treatment with oseltamivir phosphate in PANC1 cells with established resistance to cisplatin, gemcitabine, or a combination of the two agents, and in archived paraffin-embedded PANC1 tumors grown in RAGxCγ double mutant mice.Results: Oseltamivir phosphate overcame the chemoresistance of PANC1 to cisplatin and gemcitabine alone or in combination in a dose-dependent manner, and disabled the cancer cell survival mechanism(s. Oseltamivir phosphate also reversed the epithelial-mesenchymal transition characteristic of the phenotypic E-cadherin to N-cadherin changes associated with resistance to drug therapy. Low-dose oseltamivir phosphate alone or in combination with gemcitabine in heterotopic xenografts of PANC1 tumors growing in RAGxCγ double mutant mice did not prevent metastatic spread to the liver and lung.Conclusion: Therapeutic targeting of Neu1 sialidase with oseltamivir phosphate at the growth factor receptor level disables the intrinsic signaling platform for cancer cell survival

  13. Post-Acquisition IT Integration

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Yetton, Philip

    2013-01-01

    The extant research on post-acquisition IT integration analyzes how acquirers realize IT-based value in individual acquisitions. However, serial acquirers make 60% of acquisitions. These acquisitions are not isolated events, but are components in growth-by-acquisition programs. To explain how...... serial acquirers realize IT-based value, we develop three propositions on the sequential effects on post-acquisition IT integration in acquisition programs. Their combined explanation is that serial acquirers must have a growth-by-acquisition strategy that includes the capability to improve...... IT integration capabilities, to sustain high alignment across acquisitions and to maintain a scalable IT infrastructure with a flat or decreasing cost structure. We begin the process of validating the three propositions by investigating a longitudinal case study of a growth-by-acquisition program....

  14. Well logging. Acquisition and applications; Diagraphies. Acquisition et applications

    Energy Technology Data Exchange (ETDEWEB)

    Serra, O.; Serra, L.

    2001-07-01

    This reference book on wire-line and LWD well logging covers all geophysical methods of underground survey in a synthetic, visual and dynamical way. It treats of: the physical principle of well logging measurements, the different types of existing probes, the factors that can influence the measurements, and the applications of these measurements. The following well-logging methods are reviewed: resistivity; electromagnetic wave propagation; magnetic susceptibility and magnetic field; spontaneous potential; nuclear logging: natural gamma radioactivity, density logging, photoelectric index, neutron emission probes, hydrogen index or neutron porosity, neutron induced gamma spectroscopy, neutron relaxation time, NMR; acoustic measurements: sonic logging, seismic profiles; texture, structure and stratigraphy data acquisition; borehole diameter measurement; temperature measurement; wire sampling methods; place and role of well-logging in petroleum exploration; well-logging programs. (J.S.)

  15. Seismic data acquisition systems

    International Nuclear Information System (INIS)

    Kolvankar, V.G.; Nadre, V.N.; Rao, D.S.

    1989-01-01

    Details of seismic data acquisition systems developed at the Bhabha Atomic Research Centre, Bombay are reported. The seismic signals acquired belong to different signal bandwidths in the band from 0.02 Hz to 250 Hz. All these acquisition systems are built around a unique technique of recording multichannel data on to a single track of an audio tape and in digital form. Techniques of how these signals in different bands of frequencies were acquired and recorded are described. Method of detecting seismic signals and its performance is also discussed. Seismic signals acquired in different set-ups are illustrated. Time indexing systems for different set-ups and multichannel waveform display systems which form essential part of the data acquisition systems are also discussed. (author). 13 refs., 6 figs., 1 tab

  16. Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

    Science.gov (United States)

    Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

    2014-02-18

    Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU.

  17. LEGS data acquisition facility

    International Nuclear Information System (INIS)

    LeVine, M.J.

    1985-01-01

    The data acquisition facility for the LEGS medium energy photonuclear beam line is composed of an auxiliary crate controller (ACC) acting as a front-end processor, loosely coupled to a time-sharing host computer based on a UNIX-like environment. The ACC services all real-time demands in the CAMAC crate: it responds to LAMs generated by data acquisition modules, to keyboard commands, and it refreshes the graphics display at frequent intervals. The host processor is needed only for printing histograms and recording event buffers on magnetic tape. The host also provides the environment for software development. The CAMAC crate is interfaced by a VERSAbus CAMAC branch driver

  18. Acquisition IT Integration

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Øhrgaard, Christian

    2015-01-01

    of temporary agency workers. Following an analytic induction approach, theoretically grounded in the re-source-based view of the firm, we identify the complimentary and supplementary roles consultants can assume in acquisition IT integration. Through case studies of three acquirers, we investigate how...... the acquirers appropriate the use of agency workers as part of its acquisition strategy. For the investigated acquirers, assigning roles to agency workers is contingent on balancing the needs of knowledge induction and knowledge retention, as well as experience richness and in-depth under-standing. Composition...

  19. EWS/FLI1 regulates EYA3 in Ewing's sarcoma via modulation of microRNA-708, resulting in increased cell survival and chemoresistance

    Science.gov (United States)

    Robin, Tyler P; Smith, Anna; McKinsey, Erin; Reaves, Lisa; Jedlicka, Paul; Ford, Heide L.

    2012-01-01

    Ewing's sarcoma is an aggressive pediatric cancer of the bone and soft tissue, in which patients whose tumors have a poor histological response to initial chemotherapy have a poor overall prognosis. Therefore, it is important to identify molecules involved in resistance to chemotherapy. Herein, we demonstrate that the DNA-repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing's sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell of origin of Ewing's sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor. We further demonstrate that EWS/FLI1 mediates upregulation of EYA3 via repression of miR-708, a microRNA that targets the EYA3 3′UTR, rather than by binding the EYA3 promoter directly. Importantly, we demonstrate that high levels of EYA3 significantly correlate with low levels of miR-708 in Ewing's sarcoma samples, suggesting that this miR-mediated mechanism of EYA3 regulation holds true in human cancers. Because EYA proteins are important for cell survival during development, we examine, and demonstrate, that loss of EYA3 decreases survival of Ewing's sarcoma cells. Most importantly, knockdown of EYA3 in Ewing's sarcoma cells leads to sensitization to DNA-damaging chemotherapeutics used in the treatment of Ewing's sarcoma, and as expected, after chemotherapeutic treatment, EYA3 knockdown cells repair DNA damage less effectively than their control counterparts. These studies identify EYA3 as a novel mediator of chemoresistance in Ewing's sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance. PMID:22723308

  20. ACQUISITIONS LIST, MAY 1966.

    Science.gov (United States)

    Harvard Univ., Cambridge, MA. Graduate School of Education.

    THIS ACQUISITIONS LIST IS A BIBLIOGRAPHY OF MATERIAL ON VARIOUS ASPECTS OF EDUCATION. OVER 300 UNANNOTATED REFERENCES ARE PROVIDED FOR DOCUMENTS DATING MAINLY FROM 1960 TO 1966. BOOKS, JOURNALS, REPORT MATERIALS, AND UNPUBLISHED MANUSCRIPTS ARE LISTED UNDER THE FOLLOWING HEADINGS--(1) ACHIEVEMENT, (2) ADOLESCENCE, (3) CHILD DEVELOPMENT, (4)…

  1. MAST data acquisition system

    International Nuclear Information System (INIS)

    Shibaev, S.; Counsell, G.; Cunningham, G.; Manhood, S.J.; Thomas-Davies, N.; Waterhouse, J.

    2006-01-01

    The data acquisition system of the Mega-Amp Spherical Tokamak (MAST) presently collects up to 400 MB of data in about 3000 data items per shot, and subsequent fast growth is expected. Since the start of MAST operations (in 1999) the system has changed dramatically. Though we continue to use legacy CAMAC hardware, newer VME, PCI, and PXI based sub-systems collect most of the data now. All legacy software has been redesigned and new software has been developed. Last year a major system improvement was made-replacement of the message distribution system. The new message system provides easy connection of any sub-system independently of its platform and serves as a framework for many new applications. A new data acquisition controller provides full control of common sub-systems, central error logging, and data acquisition alarms for the MAST plant. A number of new sub-systems using Linux and Windows OSs on VME, PCI, and PXI platforms have been developed. A new PXI unit has been designed as a base sub-system accommodating any type of data acquisition and control devices. Several web applications for the real-time MAST monitoring and data presentation have been developed

  2. Data acquisition techniques

    International Nuclear Information System (INIS)

    Dougherty, R.C.

    1976-01-01

    Testing neutron generators and major subassemblies has undergone a transition in the past few years. Digital information is now used for storage and analysis. The key to the change is the availability of a high-speed digitizer system. The status of the Sandia Laboratory data acquisition and handling system as applied to this area is surveyed. 1 figure

  3. Surviving mergers & acquisitions.

    Science.gov (United States)

    Dixon, Diane L

    2002-01-01

    Mergers and acquisitions are never easy to implement. The health care landscape is a minefield of failed mergers and uneasy alliances generating great turmoil and pain. But some mergers have been successful, creating health systems that benefit the communities they serve. Five prominent leaders offer their advice on minimizing the difficulties of M&As.

  4. General image acquisition parameters

    International Nuclear Information System (INIS)

    Teissier, J.M.; Lopez, F.M.; Langevin, J.F.

    1993-01-01

    The general parameters are of primordial importance to achieve image quality in terms of spatial resolution and contrast. They also play a role in the acquisition time for each sequence. We describe them separately, before associating them in a decision tree gathering the various options that are possible for diagnosis

  5. Decentralized Blended Acquisition

    NARCIS (Netherlands)

    Berkhout, A.J.

    2013-01-01

    The concept of blending and deblending is reviewed, making use of traditional and dispersed source arrays. The network concept of distributed blended acquisition is introduced. A million-trace robot system is proposed, illustrating that decentralization may bring about a revolution in the way we

  6. MPS Data Acquisition System

    International Nuclear Information System (INIS)

    Eiseman, S.E.; Miller, W.J.

    1975-01-01

    A description is given of the data acquisition system used with the multiparticle spectrometer facility at Brookhaven. Detailed information is provided on that part of the system which connects the detectors to the data handler; namely, the detector electronics, device controller, and device port optical isolator

  7. [Acquisition of arithmetic knowledge].

    Science.gov (United States)

    Fayol, Michel

    2008-01-01

    The focus of this paper is on contemporary research on the number counting and arithmetical competencies that emerge during infancy, the preschool years, and the elementary school. I provide a brief overview of the evolution of children's conceptual knowledge of arithmetic knowledge, the acquisition and use of counting and how they solve simple arithmetic problems (e.g. 4 + 3).

  8. Second Language Acquisition.

    Science.gov (United States)

    McLaughlin, Barry; Harrington, Michael

    1989-01-01

    A distinction is drawn between representational and processing models of second-language acquisition. The first approach is derived primarily from linguistics, the second from psychology. Both fields, it is argued, need to collaborate more fully, overcoming disciplinary narrowness in order to achieve more fruitful research. (GLR)

  9. Data acquisition for PLT

    International Nuclear Information System (INIS)

    Thompson, P.A.

    1975-01-01

    DA/PLT, the data acquisition system for the Princeton Large Torus (PLT) fusion research device, consists of a PDP-10 host computer, five satellite PDP-11s connected to the host by a special high-speed interface, miscellaneous other minicomputers and commercially supplied instruments, and much PPPL produced hardware. The software consists of the standard PDP-10 monitor with local modifications and the special systems and applications programs to customize the DA/PLT for the specific job of supporting data acquisition, analysis, display, and archiving, with concurrent off-line analysis, program development, and, in the background, general batch and timesharing. Some details of the over-all architecture are presented, along with a status report of the different PLT experiments being supported

  10. Knowledge Transfers following Acquisition

    DEFF Research Database (Denmark)

    Gammelgaard, Jens

    2001-01-01

    Prior relations between the acquiring firm and the target company pave the way for knowledge transfers subsequent to the acquisitions. One major reason is that through the market-based relations the two actors build up mutual trust and simultaneously they learn how to communicate. An empirical...... study of 54 Danish acquisitions taking place abroad from 1994 to 1998 demonstrated that when there was a high level of trust between the acquiring firm and the target firm before the take-over, then medium and strong tie-binding knowledge transfer mechanisms, such as project groups and job rotation......, were used more intensively. Further, the degree of stickiness was significantly lower in the case of prior trust-based relations....

  11. Amplitudes, acquisition and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bloor, Robert

    1998-12-31

    Accurate seismic amplitude information is important for the successful evaluation of many prospects and the importance of such amplitude information is increasing with the advent of time lapse seismic techniques. It is now widely accepted that the proper treatment of amplitudes requires seismic imaging in the form of either time or depth migration. A key factor in seismic imaging is the spatial sampling of the data and its relationship to the imaging algorithms. This presentation demonstrates that acquisition caused spatial sampling irregularity can affect the seismic imaging and perturb amplitudes. Equalization helps to balance the amplitudes, and the dealing strategy improves the imaging further when there are azimuth variations. Equalization and dealiasing can also help with the acquisition irregularities caused by shot and receiver dislocation or missing traces. 2 refs., 2 figs.

  12. Data acquisition instruments: Psychopharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Hartley, D.S. III

    1998-01-01

    This report contains the results of a Direct Assistance Project performed by Lockheed Martin Energy Systems, Inc., for Dr. K. O. Jobson. The purpose of the project was to perform preliminary analysis of the data acquisition instruments used in the field of psychiatry, with the goal of identifying commonalities of data and strategies for handling and using the data in the most advantageous fashion. Data acquisition instruments from 12 sources were provided by Dr. Jobson. Several commonalities were identified and a potentially useful data strategy is reported here. Analysis of the information collected for utility in performing diagnoses is recommended. In addition, further work is recommended to refine the commonalities into a directly useful computer systems structure.

  13. First Language Acquisition and Teaching

    Science.gov (United States)

    Cruz-Ferreira, Madalena

    2011-01-01

    "First language acquisition" commonly means the acquisition of a single language in childhood, regardless of the number of languages in a child's natural environment. Language acquisition is variously viewed as predetermined, wondrous, a source of concern, and as developing through formal processes. "First language teaching" concerns schooling in…

  14. Multiprocessor data acquisition system

    International Nuclear Information System (INIS)

    Haumann, J.R.; Crawford, R.K.

    1987-01-01

    A multiprocessor data acquisition system has been built to replace the single processor systems at the Intense Pulsed Neutron Source (IPNS) at Argonne National Laboratory. The multiprocessor system was needed to accommodate the higher data rates at IPNS brought about by improvements in the source and changes in instrument configurations. This paper describes the hardware configuration of the system and the method of task sharing and compares results to the single processor system

  15. Implementing acquisition strategies

    International Nuclear Information System (INIS)

    Montgomery, G. K.

    1997-01-01

    The objective of this paper is to address some of the strategies necessary to effect a successful asset or corporate acquisition. Understanding the corporate objective, the full potential of the asset, the specific strategies to be employed, the value of time, and most importantly the interaction of all these are crucial, for missed steps are likely to result in missed opportunities. The amount of factual information that can be obtained and utilized in a timely fashion is the largest single hurdle to the capture of value in the asset or corporate acquisition. Fact, familiarity and experience are key in this context. The importance of the due diligence process prior to title or data transfer cannot be overemphasized. Some of the most important assets acquired in a merger may be the people. To maximize effectiveness, it is essential to merge both existing staff and those that came with the new acquisition as soon as possible. By thinking together as a unit, knowledge and experience can be applied to realize the potential of the asset. Hence team building is one of the challenges, doing it quickly is usually the most effective. Developing new directions for the new enlarged company by combining the strengths of the old and the new creates more value, as well as a more efficient operation. Equally important to maximizing the potential of the new acquisition is the maintenance of the momentum generated by the need to grow that gave the impetus to acquiring new assets in the first place. In brief, the right mix of vision, facts and perceptions, quick enactment of the post-close strategies and keeping the momentum alive, are the principal ingredients of a focused strategy

  16. Internationalize Mergers and Acquisitions

    OpenAIRE

    Zhou, Lili

    2017-01-01

    As globalization processes, an increasing number of companies use mergers and acquisitions as a tool to achieve company growth in the international business world. The purpose of this thesis is to investigate the process of an international M&A and analyze the factors leading to success. The research started with reviewing different academic theory. The important aspects in both pre-M&A phase and post-M&A phase have been studied in depth. Because of the complexity in international...

  17. Data Acquisition System

    International Nuclear Information System (INIS)

    Watwood, D.; Beatty, J.

    1991-01-01

    The Data Acquisition System (DAS) is comprised of a Hewlett-Packard (HP) model 9816, Series 200 Computer System with the appropriate software to acquire, control, and archive data from a Data Acquisition/Control Unit, models HP3497A and HP3498A. The primary storage medium is an HP9153 16-megabyte hard disc. The data is backed-up on three floppy discs. One floppy disc drive is contained in the HP9153 chassis; the other two comprise an HP9122 dual disc drive. An HP82906A line printer supplies hard copy backup. A block diagram of the hardware setup is shown. The HP3497A/3498A Data Acquisition/Control Units read each input channel and transmit the raw voltage reading to the HP9816 CPU via the HPIB bus. The HP9816 converts this voltage to the appropriate engineering units using the calibration curves for the sensor being read. The HP9816 archives both the raw and processed data along with the time and the readings were taken to hard and floppy discs. The processed values and reading time are printed on the line printer. This system is designed to accommodate several types of sensors; each type is discussed in the following sections

  18. Complexity in language acquisition.

    Science.gov (United States)

    Clark, Alexander; Lappin, Shalom

    2013-01-01

    Learning theory has frequently been applied to language acquisition, but discussion has largely focused on information theoretic problems-in particular on the absence of direct negative evidence. Such arguments typically neglect the probabilistic nature of cognition and learning in general. We argue first that these arguments, and analyses based on them, suffer from a major flaw: they systematically conflate the hypothesis class and the learnable concept class. As a result, they do not allow one to draw significant conclusions about the learner. Second, we claim that the real problem for language learning is the computational complexity of constructing a hypothesis from input data. Studying this problem allows for a more direct approach to the object of study--the language acquisition device-rather than the learnable class of languages, which is epiphenomenal and possibly hard to characterize. The learnability results informed by complexity studies are much more insightful. They strongly suggest that target grammars need to be objective, in the sense that the primitive elements of these grammars are based on objectively definable properties of the language itself. These considerations support the view that language acquisition proceeds primarily through data-driven learning of some form. Copyright © 2013 Cognitive Science Society, Inc.

  19. MDSplus data acquisition system

    International Nuclear Information System (INIS)

    Stillerman, J.A.; Fredian, T.W.; Klare, K.; Manduchi, G.

    1997-01-01

    MDSplus, a tree based, distributed data acquisition system, was developed in collaboration with the ZTH Group at Los Alamos National Lab and the RFX Group at CNR in Padua, Italy. It is currently in use at MIT, RFX in Padua, TCV at EPFL in Lausanne, and KBSI in South Korea. MDSplus is made up of a set of X/motif based tools for data acquisition and display, as well as diagnostic configuration and management. It is based on a hierarchical experiment description which completely describes the data acquisition and analysis tasks and contains the results from these operations. These tools were designed to operate in a distributed, client/server environment with multiple concurrent readers and writers to the data store. While usually used over a Local Area Network, these tools can be used over the Internet to provide access for remote diagnosticians and even machine operators. An interface to a relational database is provided for storage and management of processed data. IDL is used as the primary data analysis and visualization tool. IDL is a registered trademark of Research Systems Inc. copyright 1996 American Institute of Physics

  20. Proteomická studie mechanismů chemoresistence T-lymfoblastické leukémie k inhibitorům cyklin-dependentních kináz

    Czech Academy of Sciences Publication Activity Database

    Martinková, Jiřina; Skalníková, Helena; Halada, Petr; Novák, Petr; Hrabáková, Rita; Džubák, P.; Hajdúch, M.; Dziechciarková, M.; Kovářová, Hana

    -, č. 4 (2008), s. 24-24 ISSN 1803-5922. [Dny diagnostické, prediktivní a experimentální onkologie /4./. 26.11.2008-28.11.2008, Olomouc] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : chemoresistence Subject RIV: FD - Oncology ; Hematology

  1. Success Factors of the Companies Mergers and Acquisitions

    Directory of Open Access Journals (Sweden)

    Maria Sierpińska

    2007-01-01

    Full Text Available Mergers and acquisitions (MA are one of the most important phenomenons influencing dynamics of the world economy growth. At the same time, big number of acquisitions turns out to be unsuccessful which induces one to examine reasons for failures and factors having influence on success of MA. In the article an attempt to systematize researchers and specialists-practitioners opinions on factors that play a key role in acquisition success was made, as complexity of MA processes causes that only actions resulting from reliable analysis, that are afterwards well planned and carried out may bring results expected by the entities.

  2. The NUSTAR data acquisition

    Energy Technology Data Exchange (ETDEWEB)

    Loeher, B.; Toernqvist, H.T. [TU Darmstadt (Germany); GSI (Germany); Agramunt, J. [IFIC, CSIC (Spain); Bendel, M.; Gernhaeuser, R.; Le Bleis, T.; Winkel, M. [TU Muenchen (Germany); Charpy, A.; Heinz, A.; Johansson, H.T. [Chalmers University of Technology (Sweden); Coleman-Smith, P.; Lazarus, I.H.; Pucknell, V.F.E. [STFC Daresbury (United Kingdom); Czermak, A. [IFJ (Poland); Kurz, N.; Nociforo, C.; Pietri, S.; Schaffner, H.; Simon, H. [GSI (Germany); Scheit, H. [TU Darmstadt (Germany); Taieb, J. [CEA (France)

    2015-07-01

    The diversity of upcoming experiments within the NUSTAR collaboration, including experiments in storage rings, reactions at relativistic energies and high-precision spectroscopy, is reflected in the diversity of the required detection systems. A challenging task is to incorporate the different needs of individual detectors within the unified NUSTAR Data AcQuisition (NDAQ). NDAQ takes up this challenge by providing a high degree of availability via continuously running systems, high flexibility via experiment-specific configuration files for data streams and trigger logic, distributed timestamps and trigger information on km distances, all built on the solid basis of the GSI Multi-Branch System. NDAQ ensures interoperability between individual NUSTAR detectors and allows merging of formerly separate data streams according to the needs of all experiments, increasing reliability in NUSTAR data acquisition. An overview of the NDAQ infrastructure and the current progress is presented. The NUSTAR (NUclear STructure, Astrophysics and Reactions) collaboration represents one of the four pillars motivating the construction of the international FAIR facility. The diversity of NUSTAR experiments, including experiments in storage rings, reactions at relativistic energies and high-precision spectroscopy, is reflected in the diversity of the required detection systems. A challenging task is to incorporate the different needs of individual detectors and components under the umbrella of the unified NUSTAR Data AQuisition (NDAQ) infrastructure. NDAQ takes up this challenge by providing a high degree of availability via continuously running systems, high flexibility via experiment-specific configuration files for data streams and trigger logic, and distributed time stamps and trigger information on km distances, all built on the solid basis of the GSI Multi-Branch System (MBS). NDAQ ensures interoperability between individual NUSTAR detectors and allows merging of formerly separate

  3. TCABR data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    Fagundes, A.N. E-mail: fagundes@if.usp.br; Sa, W.P.; Coelho, P.M.S.A

    2000-08-01

    A brief description of the design of the data acquisition system for the TCABR tokamak is presented. The system comprises the VME standard instrumentation incorporating CAMAC instrumentation through the use of a GPIB interface. All the necessary data for programming different parts of the equipment, as well as the repertoire of actions for the machine control, are stored in a DBMS, with friendly interfaces. Public access software is used, where feasible, in the development of codes. The TCABR distinguished feature is the virtual lack of frontiers in upgrading, either in hardware or software.

  4. Flexible data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    Clout, P N; Ridley, P A [Science Research Council, Daresbury (UK). Daresbury Lab.

    1978-06-01

    A data acquisition system has been developed which enables several independent experiments to be controlled by a 24 K word PDP-11 computer. Significant features of the system are the use of CAMAC, a high level language (RTL/2) and a general-purpose operating system executive which assist the rapid implementation of new experiments. This system has been used successfully for EXAFS and photo-electron spectroscopy experiments. It is intended to provide powerful concurrent data analysis and feedback facilities to the experimenter by on-line connection to the central IBM 370/165 computer.

  5. Getting Defense Acquisition Right

    Science.gov (United States)

    2017-01-01

    on top of events and steer them to get where we need to go as efficiently as possible. Program management is not a spectator sport . Frank Frank...I made in the e-mail above and discusses some of the proactive steps a Program Manager can take, ahead of time , to reduce the potential...The Congress will rescind funds that are not obligated in a timely way. This puts pressure on the DoD’s acquisition managers to put money on

  6. Data-acquisition systems

    International Nuclear Information System (INIS)

    Cyborski, D.R.; Teh, K.M.

    1995-01-01

    Up to now, DAPHNE, the data-acquisition system developed for ATLAS, was used routinely for experiments at ATLAS and the Dynamitron. More recently, the Division implemented 2 MSU/DAPHNE systems. The MSU/DAPHNE system is a hybrid data-acquisition system which combines the front-end of the Michigan State University (MSU) DA system with the traditional DAPHNE back-end. The MSU front-end is based on commercially available modules. This alleviates the problems encountered with the DAPHNE front-end which is based on custom designed electronics. The first MSU system was obtained for the APEX experiment and was used there successfully. A second MSU front-end, purchased as a backup for the APEX experiment, was installed as a fully-independent second MSU/DAPHNE system with the procurement of a DEC 3000 Alpha host computer, and was used successfully for data-taking in an experiment at ATLAS. Additional hardware for a third system was bought and will be installed. With the availability of 2 MSU/DAPHNE systems in addition to the existing APEX setup, it is planned that the existing DAPHNE front-end will be decommissioned

  7. Continued Data Acquisition Development

    Energy Technology Data Exchange (ETDEWEB)

    Schwellenbach, David [National Security Technologies, LLC. (NSTec), Mercury, NV (United States)

    2017-11-27

    This task focused on improving techniques for integrating data acquisition of secondary particles correlated in time with detected cosmic-ray muons. Scintillation detectors with Pulse Shape Discrimination (PSD) capability show the most promise as a detector technology based on work in FY13. Typically PSD parameters are determined prior to an experiment and the results are based on these parameters. By saving data in list mode, including the fully digitized waveform, any experiment can effectively be replayed to adjust PSD and other parameters for the best data capture. List mode requires time synchronization of two independent data acquisitions (DAQ) systems: the muon tracker and the particle detector system. Techniques to synchronize these systems were studied. Two basic techniques were identified: real time mode and sequential mode. Real time mode is the preferred system but has proven to be a significant challenge since two FPGA systems with different clocking parameters must be synchronized. Sequential processing is expected to work with virtually any DAQ but requires more post processing to extract the data.

  8. Unsupervised Language Acquisition

    Science.gov (United States)

    de Marcken, Carl

    1996-11-01

    This thesis presents a computational theory of unsupervised language acquisition, precisely defining procedures for learning language from ordinary spoken or written utterances, with no explicit help from a teacher. The theory is based heavily on concepts borrowed from machine learning and statistical estimation. In particular, learning takes place by fitting a stochastic, generative model of language to the evidence. Much of the thesis is devoted to explaining conditions that must hold for this general learning strategy to arrive at linguistically desirable grammars. The thesis introduces a variety of technical innovations, among them a common representation for evidence and grammars, and a learning strategy that separates the ``content'' of linguistic parameters from their representation. Algorithms based on it suffer from few of the search problems that have plagued other computational approaches to language acquisition. The theory has been tested on problems of learning vocabularies and grammars from unsegmented text and continuous speech, and mappings between sound and representations of meaning. It performs extremely well on various objective criteria, acquiring knowledge that causes it to assign almost exactly the same structure to utterances as humans do. This work has application to data compression, language modeling, speech recognition, machine translation, information retrieval, and other tasks that rely on either structural or stochastic descriptions of language.

  9. Ergosterol Peroxide Isolated from Ganoderma lucidum Abolishes MicroRNA miR-378-Mediated Tumor Cells on Chemoresistance

    Science.gov (United States)

    Li, Xiang-Min; Yang, Weining; Jiao, Chun-Wei; Fang, Ling; Li, Sen-Zhu; Pan, Hong-Hui; Yee, Albert J.; Lee, Daniel Y.; Li, Chong; Zhang, Zhi; Guo, Jun; Yang, Burton B.

    2012-01-01

    Due to an altered expression of oncogenic factors and tumor suppressors, aggressive cancer cells have an intrinsic or acquired resistance to chemotherapeutic agents. This typically contributes to cancer recurrence after chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell self-renewal and cancer development. Here we report that tumor cells transfected with miR-378 acquired properties of aggressive cancer cells. Overexpression of miR-378 enhanced both cell survival and colony formation, and contributed to multiple drug resistance. Higher concentrations of chemotherapeutic drugs were needed to induce death of miR-378-transfected cells than to induce death of control cells. We found that the biologically active component isolated from Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We purified and identified the biologically active component of Ganoderma lucidum as ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater activity in inducing death of miR-378 cells than the GFP cells. Lower concentrations of ergosterol peroxide were needed to induce death of the miR-378-transfected cells than in the control cells. With further clinical development, ergosterol peroxide represents a promising new reagent that can overcome the drug-resistance of tumor cells. PMID:22952996

  10. miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling.

    Science.gov (United States)

    Lu, Meng; Wang, Chengyong; Chen, Weihui; Mao, Chuanqing; Wang, Jin

    2018-04-01

    Oral squamous cell carcinoma (OSCC) is characterized by rapid local migration and invasion. This study was aimed at clarifying the effect of miR-654-5p on progression of OSCC. miR-654-5p promoted proliferation, metastasis, and chemoresistance of OSCC in vitro and in vivo. Consistently, miR-654-5p was upregulated in late-stage OSCC and was correlated with poor prognosis of OSCC patients. Furthermore, miR-654-5p was mechanistically verified to target Grb-2-related adaptor protein (GRAP), accompanied by the activation of Ras/MAPK signaling and the facilitation of epithelial-mesenchymal transition in OSCC cells. GRAP was downregulated in T1-2 stage versus T3-4 stage head and neck squamous cell carcinoma (HNSC) and was negatively correlated with tumor-node-metastases (TNM) stage in HNSC patients based on The Cancer Genome Atlas (TCGA) analysis. In addition, GRAP was positively correlated with good prognosis in HNSC patients. Our findings suggest that the miR-654-5p/GRAP/Ras/Erk signaling pathway in OSCC cells might contribute to the underlying mechanism through which miR-654-5p participates in the regulation of OSCC progression. miR-654-5p, as a potential biomarker for the clinical diagnosis and prognosis of OSCC, may be an effective anticancer target for the treatment of OSCC.

  11. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance

    Science.gov (United States)

    Mohammed, Maryam K.; Shao, Connie; Wang, Jing; Wei, Qiang; Wang, Xin; Collier, Zachary; Tang, Shengli; Liu, Hao; Zhang, Fugui; Huang, Jiayi; Guo, Dan; Lu, Minpeng; Liu, Feng; Liu, Jianxiang; Ma, Chao; Shi, Lewis L.; Athiviraham, Aravind; He, Tong-Chuan; Lee, Michael J.

    2016-01-01

    Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis, and cell polarity. The role of Wnt signaling in control of cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway, which is the best characterized among the multiple Wnt signaling branches. The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway, as many new components of Wnt signaling have been identified and linked to signaling regulation, stem cell functions, and adult tissue homeostasis. Additionally, a substantial body of evidence links Wnt signaling to tumorigenesis of many cancer types and implicates it in the development of cancer drug resistance. Thus, a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy. This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease. We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness, tumorigenesis, and cancer drug resistance. Ultimately, we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance. PMID:27077077

  12. MACC1 facilitates chemoresistance and cancer stem cell‑like properties of colon cancer cells through the PI3K/AKT signaling pathway.

    Science.gov (United States)

    Wang, Jiankai; Wang, Wenjuan; Cai, Hongyi; Du, Binbin; Zhang, Lijuan; Ma, Wen; Hu, Yongguo; Feng, Shifang; Miao, Guoying

    2017-12-01

    With regards to colon cancer, resistance to 5‑fluorouracil (5‑FU)‑based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis‑associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC‑like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5‑FU; subsequently, CSC‑like properties and 5‑FU sensitivity were investigated. Within 5‑FU‑resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3‑kinase/protein kinase B signaling pathway may be associated with 5‑FU resistance and CSC‑like properties via MACC1.

  13. MACC1 facilitates chemoresistance and cancer stem cell-like properties of colon cancer cells through the PI3K/AKT signaling pathway

    Science.gov (United States)

    Wang, Jiankai; Wang, Wenjuan; Cai, Hongyi; Du, Binbin; Zhang, Lijuan; Ma, Wen; Hu, Yongguo; Feng, Shifang; Miao, Guoying

    2017-01-01

    With regards to colon cancer, resistance to 5-fluorouracil (5-FU)-based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis-associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC-like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5-FU; subsequently, CSC-like properties and 5-FU sensitivity were investigated. Within 5-FU-resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3-kinase/protein kinase B signaling pathway may be associated with 5-FU resistance and CSC-like properties via MACC1. PMID:28990068

  14. Collection assessment and acquisitions budgets

    CERN Document Server

    Lee, Sul H

    2013-01-01

    This invaluable new book contains timely information about the assessment of academic library collections and the relationship of collection assessment to acquisition budgets. The rising cost of information significantly influences academic libraries'abilities to acquire the necessary materials for students and faculty, and public libraries'abilities to acquire material for their clientele. Collection Assessment and Acquisitions Budgets examines different aspects of the relationship between the assessment of academic library collections and the management of library acquisition budgets. Librar

  15. Foreign Acquisition, Wages and Productivity

    DEFF Research Database (Denmark)

    Bandick, Roger

    This paper studies the effect of foreign acquisition on wages and total factor productivity (TFP) in the years following a takeover by using unique detailed firm-level data for Sweden for the period 1993-2002. The paper takes particular account of the potential endogeneity of the acquisition...

  16. Foreign Acquisition, Wages and Productivity

    DEFF Research Database (Denmark)

    Bandick, Roger

    2011-01-01

    This paper studies the effect of foreign acquisition on wages and total factor productivity (TFP) in the years following a takeover by using unique detailed firm-level data for Sweden for the period 1993-2002. The paper takes particular account of the potential endogeneity of the acquisition...

  17. Nutrient acquisition strategies of mammalian cells.

    Science.gov (United States)

    Palm, Wilhelm; Thompson, Craig B

    2017-06-07

    Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

  18. Developing Acquisition IS Integration Capabilities

    DEFF Research Database (Denmark)

    Wynne, Peter J.

    2016-01-01

    An under researched, yet critical challenge of Mergers and Acquisitions (M&A), is what to do with the two organisations’ information systems (IS) post-acquisition. Commonly referred to as acquisition IS integration, existing theory suggests that to integrate the information systems successfully......, an acquiring company must leverage two high level capabilities: diagnosis and integration execution. Through a case study, this paper identifies how a novice acquirer develops these capabilities in anticipation of an acquisition by examining its use of learning processes. The study finds the novice acquirer...... applies trial and error, experimental, and vicarious learning processes, while actively avoiding improvisational learning. The results of the study contribute to the acquisition IS integration literature specifically by exploring it from a new perspective: the learning processes used by novice acquirers...

  19. Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

    Science.gov (United States)

    Liu, Liwei; Herfindal, Lars; Jokela, Jouni; Shishido, Tania Keiko; Wahlsten, Matti; Døskeland, Stein Ove; Sivonen, Kaarina

    2014-01-01

    In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81) cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T) fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML) activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells. PMID:24705501

  20. Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Liwei Liu

    2014-04-01

    Full Text Available In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81 cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells.

  1. Gene Acquisition Convergence between Entomopoxviruses and Baculoviruses

    Directory of Open Access Journals (Sweden)

    Julien Thézé

    2015-04-01

    Full Text Available Organisms from diverse phylogenetic origins can thrive within the same ecological niches. They might be induced to evolve convergent adaptations in response to a similar landscape of selective pressures. Their genomes should bear the signature of this process. The study of unrelated virus lineages infecting the same host panels guarantees a clear identification of phyletically independent convergent adaptation. Here, we investigate the evolutionary history of genes in the accessory genome shared by unrelated insect large dsDNA viruses: the entomopoxviruses (EPVs, Poxviridae and the baculoviruses (BVs. EPVs and BVs have overlapping ecological niches and have independently evolved similar infection processes. They are, in theory, subjected to the same selective pressures from their host’s immune responses. Their accessory genomes might, therefore, bear analogous genomic signatures of convergent adaption and could point out key genomic mechanisms of adaptation hitherto undetected in viruses. We uncovered 32 homologous, yet independent acquisitions of genes originating from insect hosts, different eukaryotes, bacteria and viruses. We showed different evolutionary levels of gene acquisition convergence in these viruses, underlining a continuous evolutionary process. We found both recent and ancient gene acquisitions possibly involved to the adaptation to both specific and distantly related hosts. Multidirectional and multipartite gene exchange networks appear to constantly drive exogenous gene assimilations, bringing key adaptive innovations and shaping the life histories of large DNA viruses. This evolutionary process might lead to genome level adaptive convergence.

  2. 48 CFR 873.105 - Acquisition planning.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Acquisition planning. 873.105 Section 873.105 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS DEPARTMENT... planning. (a) Acquisition planning is an indispensable component of the total acquisition process. (b) For...

  3. 48 CFR 34.004 - Acquisition strategy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acquisition strategy. 34... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 34.004 Acquisition strategy. The program manager, as specified in agency procedures, shall develop an acquisition strategy tailored to the particular...

  4. 48 CFR 3034.004 - Acquisition strategy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Acquisition strategy. 3034.004 Section 3034.004 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Acquisition strategy. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider...

  5. 48 CFR 434.004 - Acquisition strategy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Acquisition strategy. 434.004 Section 434.004 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 434.004 Acquisition strategy. (a) The program...

  6. 48 CFR 234.004 - Acquisition strategy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Acquisition strategy. 234..., DEPARTMENT OF DEFENSE SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION 234.004 Acquisition strategy. (1) See 209.570 for policy applicable to acquisition strategies that consider the use of lead system...

  7. Trigger and data acquisition

    CERN Multimedia

    CERN. Geneva; Gaspar, C

    2001-01-01

    Past LEP experiments generate data at 0.5 MByte/s from particle detectors with over a quarter of a million readout channels. The process of reading out the electronic channels, treating them, and storing the date produced by each collision for further analysis by the physicists is called "Data Acquisition". Not all beam crossings produce interesting physics "events", picking the interesting ones is the task of the "Trigger" system. In order to make sure that the data is collected in good conditions the experiment's operation has to be constantly verified. In all, at LEP experiments over 100 000 parameters were monitored, controlled, and synchronized by the "Monotoring and control" system. In the future, LHC experiments will produce as much data in a single day as a LEP detector did in a full year's running with a raw data rate of 10 - 100 MBytes/s and will have to cope with some 800 million proton-proton collisions a second of these collisions only one in 100 million million is interesting for new particle se...

  8. DATA ACQUISITION (DAQ)

    CERN Multimedia

    Gerry Bauer

    The CMS Storage Manager System The tail-end of the CMS Data Acquisition System is the Storage Manger (SM), which collects output from the HLT and stages the data at Cessy for transfer to its ultimate home in the Tier-0 center. A SM system has been used by CMS for several years with the steadily evolving software within the XDAQ framework, but until relatively recently, only with provisional hardware. The SM is well known to much of the collaboration through the ‘MiniDAQ’ system, which served as the central DAQ system in 2007, and lives on in 2008 for dedicated sub-detector commissioning. Since March of 2008 a first phase of the final hardware was commissioned and used in CMS Global Runs. The system originally planned for 2008 aimed at recording ~1MB events at a few hundred Hz. The building blocks to achieve this are based on Nexsan's SATABeast storage array - a device  housing up to 40 disks of 1TB each, and possessing two controllers each capable of almost 200 MB/sec throughput....

  9. IPNS data acquisition system

    International Nuclear Information System (INIS)

    Worlton, T.G.; Crawford, R.K.; Haumann, J.R.; Daly, R.

    1983-01-01

    The IPNS Data Acquisition System (DAS) was designed to be reliable, flexible, and easy to use. It provides unique methods of acquiring Time-of-Flight neutron scattering data and allows collection, storage, display, and analysis of very large data arrays with a minimum of user input. Data can be collected from normal detectors, linear position-sensitive detectors, and/or area detectors. The data can be corrected for time-delays and can be time-focussed before being binned. Corrections to be made to the data and selection of inputs to be summed are entirely software controlled, as are the time ranges and resolutions for each detector element. Each system can be configured to collect data into millions of channels. Maximum continuous data rates are greater than 2000 counts/sec with full corrections, or 16,000 counts/sec for the simpler binning scheme used with area detectors. Live displays of the data may be made as a function of time, wavevector, wavelength, lattice spacing, or energy. In most cases the complete data analysis can be done on the DAS host computer. The IPNS DAS became operational for four neutron scattering instruments in 1981 and has since been expanded to seven instruments

  10. In Vitro and In Vivo Prostate Cancer Metastasis and Chemoresistance Can Be Modulated by Expression of either CD44 or CD147

    Science.gov (United States)

    Hao, Jingli; Madigan, Michele C.; Khatri, Aparajita; Power, Carl A.; Hung, Tzong-Tyng; Beretov, Julia; Chang, Lei; Xiao, Weiwei; Cozzi, Paul J.; Graham, Peter H.; Kearsley, John H.; Li, Yong

    2012-01-01

    CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX) responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment. PMID:22870202

  11. In vitro and in vivo prostate cancer metastasis and chemoresistance can be modulated by expression of either CD44 or CD147.

    Directory of Open Access Journals (Sweden)

    Jingli Hao

    Full Text Available CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP cells, their docetaxel (DTX responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD in PC-3M-luc CaP cells using short hairpin RNA (shRNA. Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2 and MCT4 (monocarboxylate tranporter-4 was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c. xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment.

  12. Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

    Science.gov (United States)

    Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

    2018-05-25

    Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

  13. Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon.

    Science.gov (United States)

    Pratt-Riccio, Lilian R; Chehuan, Yonne F; Siqueira, Maria José; das Graças Alecrim, Maria; Bianco-Junior, Cesare; Druilhe, Pierre; Brasseur, Philippe; de Fátima Ferreira-da-Cruz, Maria; Carvalho, Leonardo J M; Daniel-Ribeiro, Cláudio T

    2013-08-12

    The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10-20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.

  14. Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model

    Science.gov (United States)

    Ikram, Muhammad; Lim, Yeseon; Baek, Sun-Yong; Jin, Songwan; Jeong, Young Hun; Kwak, Jong-Young; Yoon, Sik

    2018-01-01

    Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment. Using this model, we explored strategies to enhance chemosensitivity to doxorubicin, an important chemotherapeutic drug widely used for the treatment of hematological malignancies. Lymphoma cells grown in this model exhibited excellent biomimetic properties compared to conventional 2D culture including (1) enhanced chemotherapy resistance, (2) suppressed rate of apoptosis, (3) upregulated expression of drug resistance genes (MDR1, MRP1, BCRP and HIF-1α), (4) elevated levels of tumor aggressiveness factors including Notch (Notch-1, -2, -3, and -4) and its downstream molecules (Hes-1 and Hey-1), VEGF and MMPs (MMP-2 and MMP-9), and (5) enrichment of a lymphoma stem cell population. Tiam1, a potential biomarker of tumor progression, metastasis, and chemoresistance, was activated in our 3D lymphoma model. Remarkably, we identified two synergistic therapeutic oncotargets, Tiam1 and Notch, as a strategy to combat resistance against doxorubicin in EL4 T and A20 B lymphoma. Therefore, our data suggest that our 3D lymphoma model is a promising in vitro research platform for studying lymphoma biology and therapeutic approaches. PMID:29416753

  15. Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line.

    Science.gov (United States)

    Kim, Donghwi; Park, Mineon; Jang, Hyunwoong; Hyun, Hoon; Lim, Wonbong

    2018-01-01

    Consistent with cancer stem cell theory, a small fraction of cancer cells, described as cancer stem cells (CSCs), may promote tumor recurrence and anti-cancer drug resistance. Therefore, much effort has been devoted to the development of CSC targeted therapy to vanquish drug resistance. In this study, we have investigated the effect of multiple light-emitting diode (LED) irradiation treatments with conventional anti-cancer drugs on CSC-like oral cancer cells that acquired stemness by ectopic over expression of CD133. To evaluate combined LED irradiation anti-cancer drug effects, we investigated the chemosensitizing effect of 635 nm irradiation on 5-fluorouracil (5FU)-treated KB CD133+ and KB Vec cells, interrogating the underlying molecular mechanisms associated with stemness and apoptosis that are responsible for chemopreventive activity. In addition, combination therapy with LED irradiation and 5-FU treatment was carried out in KB CD133+ and KB Vec cell-inoculated mouse models. LED irradiation of 635 nm inhibited CSC-like properties consistent with a decrease in OCT4 and NANOG protein expression, reducing colony-forming ability. In addition, LED irradiation enhanced 5-FU-induced cytotoxicity and improved 5-FU chemosensitivity in KB CD133+ via enhancement of apoptosis. These findings were validated in vivo, wherein LED irradiation combined with 5-FU treatment inhibited tumor growth in KB CD133+ -inoculated mice. Collectively, our results provide novel evidence for 635 nm irradiation-induced 5-FU chemosensitization of CSC in oral cancer. In addition, this research highlights that 635 nm LED irradiation may serve as an adjunct treatment to conventional chemotherapeutic drugs in patients with oral cancer.

  16. Acquisition: Acquisition of Targets at the Missile Defense Agency

    National Research Council Canada - National Science Library

    Ugone, Mary L; Meling, John E; James, Harold C; Haynes, Christine L; Heller, Brad M; Pomietto, Kenneth M; Bobbio, Jaime; Chang, Bill; Pugh, Jacqueline

    2005-01-01

    Who Should Read This Report and Why? Missile Defense Agency program managers who are responsible for the acquisition and management of targets used to test the Ballistic Missile Defense System should be interested in this report...

  17. An universal multi-parameter data acquisition system MOLDAS1

    International Nuclear Information System (INIS)

    Jiao Dunpang; Zhou Yanyen; Ge Wenxiu; Wang Yanyu; Yu Jusheng; Jing Lan

    1988-01-01

    MOLDAS1 is a data acquisition system to be used for data-taking from reactions induced by heavy-ion in IMP. Its configuration both on hardware and software, system control logic, data flow and functions are intraduced. System specification is discussed as well

  18. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.

    Science.gov (United States)

    Shin, Daiha; Kim, Eun Hye; Lee, Jaewang; Roh, Jong-Lyel

    2017-10-01

    Reactivation of p53 and induction of tumor cell apoptosis (RITA) is a small molecule that blocks p53-MDM2 interaction, thereby reactivating p53 in tumors. RITA can induce exclusive apoptosis in cancer cells independently of the p53 pathway; however, the resistance of cancer cells remains a major drawback. Here, we found a novel resistance mechanism of RITA treatment and an effective combined treatment to overcome RITA resistance in head and neck cancer (HNC) cells. The effects of RITA and 3-methyladenine (3-MA) were tested in different HNC cell lines, including cisplatin-resistant and acquired RITA-resistant HNC cells. The effects of each drug alone and in combination were assessed by measuring cell viability, apoptosis, cell cycle, glutathione, reactive oxygen species, protein expression, genetic inhibition of p62 and Nrf2, and a mouse xenograft model of cisplatin-resistant HNC. RITA induced apoptosis of HNC cells at different levels without significantly inhibiting normal cell viability. Following RITA treatment, RITA-resistant HNC cells exhibited a sustained expression of other autophagy-related proteins, overexpressed p62, and displayed activation of the Keap1-Nrf2 antioxidant pathway. The autophagy inhibitor 3-MA sensitized resistant HNC cells to RITA treatment via the dual inhibition of molecules related to the autophagy and antioxidant systems. Silencing of the p62 gene augmented the combined effects. The effective antitumor activity of RITA plus 3-MA was also confirmed in vivo in mouse xenograft models transplanted with resistant HNC cells, showing increased oxidative stress and DNA damage. The results indicate that RITA plus 3-MA can help overcome RITA resistance in HNC cells. This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual

  19. The Acquisition Experiences of Kazoil

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Muratbekova-Touron, Maral

    2016-01-01

    This case describes two diverging post-acquisition experiences of KazOil, an oil drilling company in Kazakhstan, in the years after the dissolution of the Soviet Union. When the company was bought by the Canadian corporation Hydrocarbons Ltd in 1996, exposed to new human resource strategies...... among students that cultural distance is not the main determinant for the success of social integration mechanisms in post-acquisition situations. On the contrary, the relationship between integration instrument and integration success is also governed by contextual factors such as the attractiveness...... of the acquisition target or state of development of HRM in the target country....

  20. Data acquisition techniques using PC

    CERN Document Server

    Austerlitz, Howard

    1991-01-01

    Data Acquisition Techniques Using Personal Computers contains all the information required by a technical professional (engineer, scientist, technician) to implement a PC-based acquisition system. Including both basic tutorial information as well as some advanced topics, this work is suitable as a reference book for engineers or as a supplemental text for engineering students. It gives the reader enough understanding of the topics to implement a data acquisition system based on commercial products. A reader can alternatively learn how to custom build hardware or write his or her own software.

  1. Bootstrapping language acquisition.

    Science.gov (United States)

    Abend, Omri; Kwiatkowski, Tom; Smith, Nathaniel J; Goldwater, Sharon; Steedman, Mark

    2017-07-01

    The semantic bootstrapping hypothesis proposes that children acquire their native language through exposure to sentences of the language paired with structured representations of their meaning, whose component substructures can be associated with words and syntactic structures used to express these concepts. The child's task is then to learn a language-specific grammar and lexicon based on (probably contextually ambiguous, possibly somewhat noisy) pairs of sentences and their meaning representations (logical forms). Starting from these assumptions, we develop a Bayesian probabilistic account of semantically bootstrapped first-language acquisition in the child, based on techniques from computational parsing and interpretation of unrestricted text. Our learner jointly models (a) word learning: the mapping between components of the given sentential meaning and lexical words (or phrases) of the language, and (b) syntax learning: the projection of lexical elements onto sentences by universal construction-free syntactic rules. Using an incremental learning algorithm, we apply the model to a dataset of real syntactically complex child-directed utterances and (pseudo) logical forms, the latter including contextually plausible but irrelevant distractors. Taking the Eve section of the CHILDES corpus as input, the model simulates several well-documented phenomena from the developmental literature. In particular, the model exhibits syntactic bootstrapping effects (in which previously learned constructions facilitate the learning of novel words), sudden jumps in learning without explicit parameter setting, acceleration of word-learning (the "vocabulary spurt"), an initial bias favoring the learning of nouns over verbs, and one-shot learning of words and their meanings. The learner thus demonstrates how statistical learning over structured representations can provide a unified account for these seemingly disparate phenomena. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Evodiamine synergizes with doxorubicin in the treatment of chemoresistant human breast cancer without inhibiting P-glycoprotein.

    Directory of Open Access Journals (Sweden)

    Shengpeng Wang

    Full Text Available Drug resistance is one of the main hurdles for the successful treatment of breast cancer. The synchronous targeting of apoptosis resistance and survival signal transduction pathways may be a promising approach to overcome drug resistance. In this study, we determined that evodiamine (EVO, a major constituent of the Chinese herbal medicine Evodiae Fructus, could induce apoptosis of doxorubicin (DOX-sensitive MCF-7 and DOX-resistant MCF-7/ADR cells in a caspase-dependent manner, as confirmed by significant increases of cleaved poly(ADP-ribose polymerase (PARP, caspase-7/9, and caspase activities. Notably, the reversed phenomenon of apoptosis resistance by EVO might be attributed to its ability to inhibit the Ras/MEK/ERK pathway and the expression of inhibitors of apoptosis (IAPs. Furthermore, our results indicated that EVO enhanced the apoptotic action of DOX by inhibiting the Ras/MEK/ERK cascade and the expression of IAPs without inhibiting the expression and activity of P-glycoprotein (P-gp. Taken together, our data indicate that EVO, a natural product, may be useful applied alone or in combination with DOX for the treatment of resistant breast cancer.

  3. Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

    Science.gov (United States)

    Ju, Jingfang

    2018-01-01

    Background Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer. Materials and methods In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo. We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1). Results Mimic-1 is a strong therapeutic candidate with a number of unique features. Mimic-1 can be delivered to cancer cells without any transfection reagents (e.g. lipids, viral vector, nanoparticles). Mimic-1 is more potent at inhibiting cell proliferation and inducing cell cycle arrest at G1 phase than native miR-129 and the other mimics tested, while retaining target specificity. Mimic-1 prevents colon cancer metastasis in vivo without toxicity. Conclusion This represents a significant advancement in the development of a nontoxic and highly potent miRNA based cancer therapeutics and establishes a foundation for further developing Mimic-1 as a novel anti-cancer therapeutic for treating colorectal cancer. PMID:29507661

  4. TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo.

    Science.gov (United States)

    Alvero, Ayesha B; Heaton, Andrew; Lima, Eydis; Pitruzzello, Mary; Sumi, Natalia; Yang-Hartwich, Yang; Cardenas, Carlos; Steinmacher, Sahra; Silasi, Dan-Arin; Brown, David; Mor, Gil

    2016-06-01

    Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Evolutionary Acquisition and Spiral Development Tutorial

    National Research Council Canada - National Science Library

    Hantos, P

    2005-01-01

    .... NSS Acquisition Policy 03-01 provided some space-oriented customization and, similarly to the original DOD directives, also positioned Evolutionary Acquisition and Spiral Development as preferred...

  6. Platform attitude data acquisition system

    Digital Repository Service at National Institute of Oceanography (India)

    Afzulpurkar, S.

    A system for automatic acquisition of underwater platform attitude data has been designed, developed and tested in the laboratory. This is a micro controller based system interfacing dual axis inclinometer, high-resolution digital compass...

  7. Portable Data Acquisition System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Armstrong researchers have developed a portable data acquisition system (PDAT) that can be easily transported and set up at remote locations to display and archive...

  8. New KENS data acquisition system

    International Nuclear Information System (INIS)

    Arai, M.; Furusaka, M.; Satoh, S.

    1989-01-01

    In this report, the authors discuss a data acquisition system, KENSnet, which is newly introduced to the KENS facility. The criteria for the data acquisition system was about 1 MIPS for CPU speed and 150 Mbytes for storage capacity for a computer per spectrometer. VAX computers were chosen with their propreitary operating system, VMS. The Vax computers are connected by a DECnet network mediated by Ethernet. Front-end computers, Apple Macintosh Plus and Macintosh II, were chosen for their user-friendly manipulation and intelligence. New CAMAC-based data acquisition electronics were developed. The data acquisition control program (ICP) and the general data analysis program (Genie) were both developed at ISIS and have been installed. 2 refs., 3 figs., 1 tab

  9. Oxytocin differentially modulates pavlovian cue and context fear acquisition.

    Science.gov (United States)

    Cavalli, Juliana; Ruttorf, Michaela; Pahi, Mario Rosero; Zidda, Francesca; Flor, Herta; Nees, Frauke

    2017-06-01

    Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety. © The Author (2017). Published by Oxford University Press.

  10. Processes Asunder: Acquisition & Planning Misfits

    Science.gov (United States)

    2009-03-26

    Establishing six Business Enterprise Priorities ( BEPs ) to focus the Department’s business transformation efforts, which now guide DoD investment decisions...three phases which look very much like Milestone A, B, and C of the previously existing Life Cycle Management Framework . With this obvious redundancy...February 2002). 30 6 Defense Acquisition University, “Integrated Defense Acquisition, Technology, & Logistics Life Cycle Management Framework , version 5.2

  11. Performance Confirmation Data Acquisition System

    International Nuclear Information System (INIS)

    D.W. Markman

    2000-01-01

    The purpose of this analysis is to identify and analyze concepts for the acquisition of data in support of the Performance Confirmation (PC) program at the potential subsurface nuclear waste repository at Yucca Mountain. The scope and primary objectives of this analysis are to: (1) Review the criteria for design as presented in the Performance Confirmation Data Acquisition/Monitoring System Description Document, by way of the Input Transmittal, Performance Confirmation Input Criteria (CRWMS M and O 1999c). (2) Identify and describe existing and potential new trends in data acquisition system software and hardware that would support the PC plan. The data acquisition software and hardware will support the field instruments and equipment that will be installed for the observation and perimeter drift borehole monitoring, and in-situ monitoring within the emplacement drifts. The exhaust air monitoring requirements will be supported by a data communication network interface with the ventilation monitoring system database. (3) Identify the concepts and features that a data acquisition system should have in order to support the PC process and its activities. (4) Based on PC monitoring needs and available technologies, further develop concepts of a potential data acquisition system network in support of the PC program and the Site Recommendation and License Application

  12. A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome

    International Nuclear Information System (INIS)

    Faul, Clare; Gerszten, Kristina; Edwards, Robert; Land, Stephanie; D'Angelo, Gina M.S.; Kelley, Joseph; Price, Fredric

    2000-01-01

    Purpose: Radiation therapy can provide useful palliation in chemorefractory ovarian cancer patients. The purpose of this study was to prospectively study the palliative effect of a hypofractionated radiation treatment regimen. Change in quality-of-life scores (Functional Assessment of Cancer Therapy [FACT], Karnofsky scale), pain score, and tolerance to therapy were also assessed. Methods and Materials: A single-institution Phase I/II trial was initiated in patients with chemoresistant recurrent or progressive ovarian cancer. All patients had symptomatic and measurable intra-abdominal disease. Patients were treated with a single radiation fraction (700 cGy) or two fractions (300 cGy twice a day) to the whole abdomen over 1 day. Quality-of-life scale (FACT G version 2) was assessed at baseline and 1 and 3 months following treatment. Karnofsky scale and pain score were also evaluated in the same time frame. Results: Sixteen patients were prospectively entered into this protocol between February 1996 and September 1998. Twelve patients received a single 700 cGy fraction and four 300 cGy twice a day. All were heavily pretreated and 9 (56%) had a poor performance status prior to treatment. Symptoms needing palliation included pain (14), ascites (10), and bleeding (2). Symptomatic improvement occurred in all patients with pain (5 complete response [CR] and 7 partial response [PR], all patients with bleeding (CR 2), and two (20%) with ascites. Five patients (31%) had a reduction in lesion size documented radiologically in three. The mean duration of response was 22 weeks in patients with a Karnofsky score >70. Thirteen patients developed transient nausea and vomiting which resolved in 48 hours in all. All patients developed a transient lymphopenia. Thirteen patients completed a follow-up quality-of-life scale. There was an improvement in the physical and functional components of the scale in patients with Karnofsky score of 90-100. There was no improvement in quality of

  13. Microcomputer data acquisition and control.

    Science.gov (United States)

    East, T D

    1986-01-01

    In medicine and biology there are many tasks that involve routine well defined procedures. These tasks are ideal candidates for computerized data acquisition and control. As the performance of microcomputers rapidly increases and cost continues to go down the temptation to automate the laboratory becomes great. To the novice computer user the choices of hardware and software are overwhelming and sadly most of the computer sales persons are not at all familiar with real-time applications. If you want to bill your patients you have hundreds of packaged systems to choose from; however, if you want to do real-time data acquisition the choices are very limited and confusing. The purpose of this chapter is to provide the novice computer user with the basics needed to set up a real-time data acquisition system with the common microcomputers. This chapter will cover the following issues necessary to establish a real time data acquisition and control system: Analysis of the research problem: Definition of the problem; Description of data and sampling requirements; Cost/benefit analysis. Choice of Microcomputer hardware and software: Choice of microprocessor and bus structure; Choice of operating system; Choice of layered software. Digital Data Acquisition: Parallel Data Transmission; Serial Data Transmission; Hardware and software available. Analog Data Acquisition: Description of amplitude and frequency characteristics of the input signals; Sampling theorem; Specification of the analog to digital converter; Hardware and software available; Interface to the microcomputer. Microcomputer Control: Analog output; Digital output; Closed-Loop Control. Microcomputer data acquisition and control in the 21st Century--What is in the future? High speed digital medical equipment networks; Medical decision making and artificial intelligence.

  14. 48 CFR 970.2301 - Sustainable acquisition.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Sustainable acquisition. 970.2301 Section 970.2301 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY..., Renewable Energy Technologies, Occupational Safety and Drug-Free Work Place 970.2301 Sustainable acquisition...

  15. Program design of data acquisition in Windows

    International Nuclear Information System (INIS)

    Cai Jianxin; Yan Huawen

    2004-01-01

    Several methods for the design of data acquisition program based on Microsoft Windows are introduced. Then their respective advantages and disadvantages are totally analyzed. At the same time, the data acquisition modes applicable to each method are also pointed out. It is convenient for data acquisition programmers to develop data acquisition systems. (authors)

  16. Sustaining an Acquisition-based Growth Strategy

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Toppenberg, Gustav; Shanks, Graeme

    Value creating acquisitions are a major challenge for many firms. Our case study of Cisco Systems shows that an advanced Enterprise Architecture (EA) capability can contribute to the acquisition process through a) preparing the acquirer to become ‘acquisition ready’, b) identifying resource...... complementarity, c) directing and governing the integration process, and d) post-acquisition evaluation of the achieved integration and proposing ways forward. Using the EA capability in the acquisition process improves Cisco’s ability to rapidly capture value from its acquisitions and to sustain its acquisition...

  17. KENS data acquisition system KENSnet

    International Nuclear Information System (INIS)

    Arai, Masatoshi; Furusaka, Michihiro; Satoh, Setsuo; Johnson, M.W.

    1988-01-01

    The installation of a new data acquisition system KENSnet has been completed at the KENS neutron facility. For data collection, 160 Mbytes are necessary for temporary disk storage, and 1 MIPS of CPU is required. For the computing system, models were chosen from the VAX family of computers running their proprietary operating system VMS. The VMS operating system has a very user friendly interface, and is well suited to instrument control applications. New data acquisition electronics were developed. A gate module receives a signal of proton extraction time from the accelerator, and checks the veto signals from the sample environment equipment (vacuum, temperature, chopper phasing, etc.). Then the signal is issued to a delay-time module. A time-control module starts timing from the delayed start signal from the delay-time module, and distributes an encoded time-boundary address to memory modules at the preset times anabling the memory modules to accumulate data histograms. The data acquisition control program (ICP) and the general data analysis program (Genie) were both developed at ISIS, and have been installed in the new data acquisition system. They give the experimenter 'user-friendly' data acquisition and a good environment for data manipulation. The ICP controls the DAE and transfers the histogram data into the computers. (N.K.)

  18. The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells

    Directory of Open Access Journals (Sweden)

    S. J. Chatterjee

    2011-01-01

    Full Text Available Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible, and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

  19. Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

    Science.gov (United States)

    Zhong, Zhang-Feng; Yu, Hai-Bing; Wang, Chun-Ming; Qiang, Wen-An; Wang, Sheng-Peng; Zhang, Jin-Ming; Yu, Hua; Cui, Liao; Wu, Tie; Li, De-Qiang; Wang, Yi-Tao

    2017-01-01

    Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae . Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.

  20. The meteorological data acquisition system

    International Nuclear Information System (INIS)

    Bouharrour, S.; Thomas, P.

    1975-07-01

    The 200 m meteorological tower of the Karlsruhe Nuclear Research Center has been equipped with 45 instruments measuring the meteorological parameters near the ground level. Frequent inquiry of the instruments implies data acquisition with on-line data reduction. This task is fulfilled by some peripheral units controlled by a PDP-8/I. This report presents details of the hardware configuration and a short description of the software configuration of the meteorological data acquisition system. The report also serves as an instruction for maintenance and repair work to be carried out at the system. (orig.) [de

  1. The FINUDA data acquisition system

    International Nuclear Information System (INIS)

    Cerello, P.; Marcello, S.; Filippini, V.; Fiore, L.; Gianotti, P.; Raimondo, A.

    1996-07-01

    A parallel scalable Data Acquisition System, based on VME, has been developed to be used in the FINUDA experiment, scheduled to run at the DAPHNE machine at Frascati starting from 1997. The acquisition software runs on embedded RTPC 8067 processors using the LynxOS operating system. The readout of event fragments is coordinated by a suitable trigger Supervisor. data read by different controllers are transported via dedicated bus to a Global Event Builder running on a UNIX machine. Commands from and to VME processors are sent via socket based network protocols. The network hardware is presently ethernet, but it can easily changed to optical fiber

  2. A review of spelling acquisition

    DEFF Research Database (Denmark)

    Dich, Nadya; Cohn, Abigail C.

    2013-01-01

    This review article discusses how empirical data on the acquisition of spelling by children inform the question of the psycholinguistic validity of the phoneme, a concept central (at least implicitly) to most phonological theories. The paper reviews data on children's early spelling attempts...... literacy factors into modeling phonological knowledge. In this article, we show that the spelling acquisition data support and are best accounted for by models allowing for a hierarchy of representations, that learning to read and write has a profound effect on the phonological knowledge of an adult...

  3. [First language acquisition research and theories of language acquisition].

    Science.gov (United States)

    Miller, S; Jungheim, M; Ptok, M

    2014-04-01

    In principle, a child can seemingly easily acquire any given language. First language acquisition follows a certain pattern which to some extent is found to be language independent. Since time immemorial, it has been of interest why children are able to acquire language so easily. Different disciplinary and methodological orientations addressing this question can be identified. A selective literature search in PubMed and Scopus was carried out and relevant monographies were considered. Different, partially overlapping phases can be distinguished in language acquisition research: whereas in ancient times, deprivation experiments were carried out to discover the "original human language", the era of diary studies began in the mid-19th century. From the mid-1920s onwards, behaviouristic paradigms dominated this field of research; interests were focussed on the determination of normal, average language acquisition. The subsequent linguistic period was strongly influenced by the nativist view of Chomsky and the constructivist concepts of Piaget. Speech comprehension, the role of speech input and the relevance of genetic disposition became the centre of attention. The interactionist concept led to a revival of the convergence theory according to Stern. Each of these four major theories--behaviourism, cognitivism, interactionism and nativism--have given valuable and unique impulses, but no single theory is universally accepted to provide an explanation of all aspects of language acquisition. Moreover, it can be critically questioned whether clinicians consciously refer to one of these theories in daily routine work and whether therapies are then based on this concept. It remains to be seen whether or not new theories of grammar, such as the so-called construction grammar (CxG), will eventually change the general concept of language acquisition.

  4. Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice

    International Nuclear Information System (INIS)

    Jin Jie; Wang Yu; Xu Yang; Chen Shilei; Wang Junping; Ran Xinze; Su Yongping; Wang Jin

    2014-01-01

    Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3 -/- ) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3 -/- mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3 -/- mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury. (author)

  5. Hospital Acquisitions Before Healthcare Reform.

    Science.gov (United States)

    McCue, Michael J; Thompson, Jon M; Kim, Tae Hyun

    2015-01-01

    The hospital industry has experienced increased consolidation in the past 20 years. Since 2010, in particular, there has been a large rise in the number of hospital acquisitions, and observers have suggested this is due in part to the expected impact of federal healthcare reform legislation. This article reports on a study undertaken to identify the market, management, and financial factors affecting acute care, community hospitals acquired between 2010 and 2012. We identified 77 such hospitals and compared them to other acute care facilities. To assess how different factors were associated with acquisitions, the study used multiple logistic regressions whereby market factors were included first, followed by management and financial factors. Study findings show that acquired hospitals were located in markets with lower rates of preferred provider organization (PPO) penetration compared with nonacquired hospitals. Occupancy rate was found to be inversely related to acquisition rate; however, case-mix index was significantly and positively related to a hospital's being acquired. Financial factors negatively associated with a hospital's being acquired included age of plant and cash flow margin. In contrast to the findings from earlier studies of hospital acquisitions, our results showed that acquired hospitals possessed newer assets. However, similar to the findings of other studies, the cash flow margin of acquired hospitals was lower than that of nonacquired facilities.

  6. Organizational Learning through Knowledge Acquisitions

    NARCIS (Netherlands)

    Amiryany Araghy, N.; Huysman, M.H.; de Man, A.P.; Cloodt, M.; Vrontis, D.; Weber, Y.; Kaufmann, R.; Tarba, S.

    2008-01-01

    Many acquisitions in the high-tech industry are motivated by a desire to share knowledge in order to stimulate organizational learning, with the ultimate aim of innovation. However, acquiring a firm does not guarantee that valuable knowledge will be successfully shared. Recent research has in fact

  7. Data Acquisition and Flux Calculations

    DEFF Research Database (Denmark)

    Rebmann, C.; Kolle, O; Heinesch, B

    2012-01-01

    In this chapter, the basic theory and the procedures used to obtain turbulent fluxes of energy, mass, and momentum with the eddy covariance technique will be detailed. This includes a description of data acquisition, pretreatment of high-frequency data and flux calculation....

  8. Essays on mergers and acquisitions

    NARCIS (Netherlands)

    Faelten, A.I.

    2016-01-01

    “Essays on Mergers and Acquisitions" tackles some of the most prominent business challenges related to M&A activity. The Introduction examines the reasons why deals fail through well-known case studies; Chapter 1 presents a new index measuring countries M&A maturity worldwide; Chapter 2 focus on the

  9. Ion implantation data acquisition system

    International Nuclear Information System (INIS)

    Struttmann, D.A.; Anderl, R.A.

    1989-01-01

    This paper describes a data acquisition system developed for hydrogen ion-driven permeation experiments for materials relevant to fusion technology. The system consists of an IMB PC-AT, CAMAC interface to diagnostic instrumentation and custom-developed software (BASIC) to provide time-history information for signals from several instruments including three quadrupole mass spectrometers. 4 refs., 5 figs

  10. Data acquisition systems at Fermilab

    International Nuclear Information System (INIS)

    Votava, M.

    1999-01-01

    Experiments at Fermilab require an ongoing program of development for high speed, distributed data acquisition systems. The physics program at the lab has recently started the operation of a Fixed Target run in which experiments are running the DART[1] data acquisition system. The CDF and D experiments are preparing for the start of the next Collider run in mid 2000. Each will read out on the order of 1 million detector channels. In parallel, future experiments such as BTeV R ampersand D and Minos have already started prototype and test beam work. BTeV in particular has challenging data acquisition system requirements with an input rate of 1500 Gbytes/sec into Level 1 buffers and a logging rate of 200 Mbytes/sec. This paper will present a general overview of these data acquisition systems on three fronts those currently in use, those to be deployed for the Collider Run in 2000, and those proposed for future experiments. It will primarily focus on the CDF and D architectures and tools

  11. Language Acquisition and Language Revitalization

    Science.gov (United States)

    O'Grady, William; Hattori, Ryoko

    2016-01-01

    Intergenerational transmission, the ultimate goal of language revitalization efforts, can only be achieved by (re)establishing the conditions under which an imperiled language can be acquired by the community's children. This paper presents a tutorial survey of several key points relating to language acquisition and maintenance in children,…

  12. Advanced IPNE data acquisition system

    International Nuclear Information System (INIS)

    Duma, M.; Moisa, D.; Petrovici, M.; Berceanu, I.; Ivascu, M.; Pascovici, G.; Simion, V.; Osvath, E.; Bock, R.; Gobbi, A.; Hildebrand, K.D.; Lynen, U.; Mueller, W.F.J.; Beeskow, M.

    1987-05-01

    A complex and flexible data acquisition system has been developed in order to run relative complex experiments in our acceleration system - ALIGATOR. AIDA programme has been carried out on a small PDP - 11/34 computer and is based on a CAMAC hardware. The main hardware and software features are presented. (authors)

  13. Multiscattering illumination in blended acquisition

    NARCIS (Netherlands)

    Berkhout, A.J.; Blacquiere, G.; Verschuur, D.J.

    2012-01-01

    In traditional seismic surveys, the firing time between shots is such that the shot records do not interfere in time. However, in the concept of blended acquisition, the records do overlap, allowing denser source sampling and wider azimuths in an economic way. A denser shot sampling and wider

  14. The SINQ data acquisition environment

    Energy Technology Data Exchange (ETDEWEB)

    Maden, D [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1996-11-01

    The data acquisition environment for the neutron scattering instruments supported by LNS at SINQ is described. The intention is to provide future users with the necessary background to the computing facilities on site rather than to present a user manual for the on-line system. (author) 5 figs., 6 refs.

  15. More Mergers,More Acquisitions

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China aims to maintain sound development of the national economy through M&As Anew round of corporate mergers and acquisitions (M&As) is on the way. On September 6, the State Council announced that it would require companies in the automobile, iron and steel, cement, machinery manufacturing, electro- lytic aluminum and rare earth industries to accelerate M&As.

  16. More Mergers,More Acquisitions

    Institute of Scientific and Technical Information of China (English)

    LAN XINZHEN

    2010-01-01

    @@ A new round of corporate mergers and acquisitions(M&As)is on the way.On September 6,the State Council announced that it would require companies in the automobile,iron and steel,cement,machinery manufacturing,electrolytic aluminum and rare earth industries to accelerate M&As.

  17. E802 data acquisition complex

    International Nuclear Information System (INIS)

    LeVine, M.J.

    1985-01-01

    The data acquisition architecture planned for experiment E802 is described. A VAX 11/785 will be front-ended by a VME-based array of 68000-family microprocessors, which will be used as intelligent CAMAC crate controllers, event builders, and to augment the computing power of the VAX for on-line analysis of the data. 4 refs

  18. Strategic and Nonstrategic Information Acquisition.

    Science.gov (United States)

    Berger, Charles R.

    2002-01-01

    Uses dual-process theories and research concerned with automaticity and the role conceptual short-term memory plays in visual information processing to illustrate both the ubiquity of nonstrategic information acquisition during interpersonal communication and its potential consequences on judgments and behavior. Discusses theoretical and…

  19. The SINQ data acquisition environment

    International Nuclear Information System (INIS)

    Maden, D.

    1996-01-01

    The data acquisition environment for the neutron scattering instruments supported by LNS at SINQ is described. The intention is to provide future users with the necessary background to the computing facilities on site rather than to present a user manual for the on-line system. (author) 5 figs., 6 refs

  20. Data Acquisition for Modular Biometric Monitoring System

    Science.gov (United States)

    Chmiel, Alan J. (Inventor); Humphreys, Bradley T. (Inventor); Grodsinsky, Carlos M. (Inventor)

    2014-01-01

    A modular system for acquiring biometric data includes a plurality of data acquisition modules configured to sample biometric data from at least one respective input channel at a data acquisition rate. A representation of the sampled biometric data is stored in memory of each of the plurality of data acquisition modules. A central control system is in communication with each of the plurality of data acquisition modules through a bus. The central control system is configured to collect data asynchronously, via the bus, from the memory of the plurality of data acquisition modules according to a relative fullness of the memory of the plurality of data acquisition modules.

  1. Diagnosis of respiratory epithelial clearance abnormality in patients suffering from chemo-resistant pulmonary tuberculosis with comorbidity of bronchial mucosa O. M. Raznatovska, V. M. Khlystun

    Directory of Open Access Journals (Sweden)

    O. M. Raznatovska

    2018-04-01

    Full Text Available Respiratory epithelial clearance timely and early disorder diagnosis in patients suffering from chemo-resistant pulmonary tuberculosis (CRPTB concomitant pathology of the bronchial mucosa is an actual problem of modern phthisiology, the solution of which will allow the timely application of rational correction, which will increase the effectiveness of this category treatment among patients. Objective is to investigate the nature and features of respiratory epithelial clearance disorders among patients suffering from CRPTB with comorbidity of the bronchi mucous membrane by using the developed method of these disorders diagnosis. Materials and methods. The respiratory epithelial clearance state diagnosis was carried out among 133 patients with CRPTB at the beginning of the intensive phase of antimycobacterial therapy during fibrobronchoscopy, provided there is a concomitant specific pathology of the mucous membrane (including its combination with non-specific endobronchitis. Average age of patients was 36.5 ± 1.1 years old. There were 89 (66.9 % men and 44 (33.1 % women. The tracheobronchial tree diagnostic fibrobronchoscopy with further study of the respiratory epithelial clearance condition among patients suffering from CRPTB was carried out by V. M. Khlystun at Phthisiology and Pulmonology Department of Zaporizhzhia State Medical University in CI “Zaporizhzhia Regional Antituberculous Clinical Dispensary”. Criteria of patients including into the research: existence of resistance of tuberculosis mycobacteria to anti-mycobacterial drugs in patients with new and repeated cases of tuberculosis, existence of pathology of the mucosa of bronchi confirmed during fiberoptic bronchoscopy. Serious associated diseases (HIV infection/AIDS, diabetes mellitus, etc. were criteria of exception. The condition of bronchial mucosa was studied under narcotic anaesthesia by fiberoptic bronchoscopes of Olympus (Japan. Pathology of a bronchial tree was described

  2. The effectiveness of endobronchial therapy in patients with chemo-resistant tuberculosis when specific process is localized in the lungs apical segments

    Directory of Open Access Journals (Sweden)

    V. M. Khlystun

    2017-08-01

    Full Text Available Objective – to study the effectiveness of the additional methods of endobronchial pathology treatment in patients with chemo-resistant tuberculosis (CRTB of lungs, that aimed to treat a specific process in bronchi when destructions are localized in the apical segments (S1+2 of lungs. Materials and methods. In order to investigate effectiveness of the additional methods of endobronchial pathology treatment of bronchial mucosa 79 patients with CRTB of lungs were examined. They were divided into 3 groups: basic 1 group, which included 27 patients who were treated by using antimycobacterial drugs endobronchial introduction to S1+2 with further implementation of intraorganic electrophoresis in S1+2 zone in combination with systemic receiving of antimycobacterial drugs; the comparison basic 2 group 27 patients who were treated with systemic antimycobacterial therapy in combination with antituberculosis drugs inhalations; and the group included – 25 patients who received only systemic antimycobacterial therapy. Groups were compared by the severity of the process, age and gender. Tracheobronchial tree fiber-bronchoscopy in patients with CRTB of lungs was carried out on the basis of phthisiology and pulmonology department of ZSMU in communal institution "Zaporizhzhia regional antituberculosis dispensary", by the author on their own. Character of bronchial mucosa was examined under anesthesia by fiber-bronchoscopes of company "Olympus" (Japan. Bronchial tree pathology was described according to N. V. Shesterynoy, A. N. Kaliuk (1975 classification. Results of the study were processed with modern methods of analysis on a personal computer with using the Statistical Package license software Statistica® for Windows 6.0 (StatSoft Inc., № AXXR712 D833214FAN5. Results. The use of antimycobacterial drugs endobronchial introduction to S1+2 with further implementation of intraorganic electrophoresis in S1+2 zone contributed significantly increase the

  3. 78 FR 32214 - Land Acquisitions: Appeals of Land Acquisition Decisions

    Science.gov (United States)

    2013-05-29

    ...; 134D0102DR-DS5A300000-DR.5A311.IA000113; Docket ID: BIA-2013-0005] RIN 1076-AF15 Land Acquisitions: Appeals... trust under this part, including broadening notice of any right to file an administrative appeal. DATES... the United States acquired title. See, e.g., Neighbors for Rational Dev., Inc. v. Norton, 379 F.3d 956...

  4. 48 CFR 307.104-70 - Acquisition strategy.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Acquisition strategy. 307... AND ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Planning 307.104-70 Acquisition strategy... designated by the HHS CIO, DASFMP, the CAO, or the cognizant HCA) shall prepare an acquisition strategy using...

  5. 48 CFR 207.401 - Acquisition considerations.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Equipment Lease or Purchase 207.401... prepare and provide the contracting officer with the justification supporting the decision to lease or purchase. ...

  6. 32 CFR 644.7 - Acquisition lines.

    Science.gov (United States)

    2010-07-01

    ... HANDBOOK Project Planning Civil Works § 644.7 Acquisition lines. (a) Tentative acquisition lines. As..., in accordance with sound real estate practices. Accordingly, fringe tracts will not be acquired until...

  7. Acquisition: Direct Care Medical Services Contracts

    National Research Council Canada - National Science Library

    Young, Shelton R; Joseph, Michael A; Grady, Scott J; Borum, Dawn; Parrish, Robin; Epps, John S; Lanyi, William F; Whitehead, Lynnell E; Zahn, Eva M; Shifflett, Elizabeth L

    2004-01-01

    The Under Secretary of Defense for Acquisition, Technology, and Logistics is the adviser to the Secretary and the Deputy Secretary of Defense for all matters relating to the DoD acquisition system and to procurement...

  8. Acquisition management of the Global Transportation Network

    Science.gov (United States)

    2001-08-02

    This report discusses the acquisition management of the Global transportation Network by the U.S. Transportation Command. This report is one in a series of audit reports addressing DoD acquisition management of information technology systems. The Glo...

  9. SCI based data acquisition architectures

    International Nuclear Information System (INIS)

    Bogaerts, J.A.C.; Divia, R.; Renardy, J.F.

    1992-01-01

    This paper discusses the Scalable Coherent Interface (SCI), an IEEE proposed standard (P1596) for interconnecting multiprocessor systems. The standard defines point to point connections between nodes, which can be processors, memories or I/O devices. Networks containing a maximum of 64K nodes with a bandwidth of one Gbyte/s between nodes, may be constructed. SCI is an attractive candidate to serve as a backbone for high speed, large volume data acquisition systems such as required by future experiments at the proposed Large Hadron Collider (LHC) at CERN. Work has started to simulate SCI based architectures for data acquisition systems. The simulation program proved to be a useful tool to study SCI systems. First results are reported on a model of a large LHC experiment containing over 1000 nodes

  10. Comet-Narval acquisition notice

    International Nuclear Information System (INIS)

    Le Bris, J.; Sellem, R.; Artiges, J.C.; Clavelin, J.F.; Du, S.; Grave, X.; Hubert, O.; Sauvage, J.; Roussiere, B.

    2006-01-01

    The COMET cards (encoding and time marking) serve to determine the energies and the time correlations of radiations detected during a multiparameter experiment while avoiding any extra specific module like coincidence circuits or delays) to set this time correlation. For each detected radiation, the arrival time information as well as the amplitude of the detected signal, are encoded. The results of these amplitude and time coding are associated to create an event. In this way, each detector is an independent source which provides a building block of the general information obtained by all the detectors. The COMET cards are associated with a NARVAL data acquisition system. This document is the instruction booklet of the COMET-NARVAL acquisition system

  11. Is merging and acquisition profitable?

    International Nuclear Information System (INIS)

    Skjeret, Frode; Soergard, Lars

    2002-01-01

    This report deals with mergers and acquisitions in the electricity sector in Norway. The background is the fact that the profitability of these activities proves to be low. In buying, it is typically the selling shareholder who profits from the transaction, while the buying company does not really earn much. This result appears to be a robust result both in different countries, between sectors and independent of methodology. The report provides theoretical justification for merging and buying up and empirical evaluations of the effects of company integration. It is asserted that what can be learned in general from the literature may also occur in the European power sector. Furthermore, the report discusses the challenges faced by the companies if they want to expand through mergers and acquisitions

  12. COLDEX New Data Acquisition Framework

    CERN Document Server

    Grech, Christian

    2015-01-01

    COLDEX (COLD bore EXperiment) is an experiment of the TE-VSC group installed in the Super Proton Synchrotron (SPS) which mimics a LHC type cryogenic vacuum system. In the framework of the High Luminosity upgrade of the LHC (HL-LHC project), COLDEX has been recommissioned in 2014 in order to validate carbon coatings performances at cryogenic temperature with LHC type beams. To achieve this mission, a data acquisition system is needed to retrieve and store information from the different experiment’s systems (vacuum, cryogenics, controls, safety) and perform specific calculations. This work aimed to completely redesign, implement, test and operate a brand new data acquisition framework based on communication with the experiment’s PLCs for the devices potentially available over network. The communication protocol to the PLCs is based on data retrieval both from CERN middleware infrastructures (CMW, JAPC) and on a novel open source Simatic S7 data exchange package over TCP/IP (libnodave).

  13. The ALICE data acquisition system

    CERN Document Server

    Carena, F; Chapeland, S; Chibante Barroso, V; Costa, F; Dénes, E; Divià, R; Fuchs, U; Grigore, A; Kiss, T; Simonetti, G; Soós, C; Telesca, A; Vande Vyvre, P; Von Haller, B

    2014-01-01

    In this paper we describe the design, the construction, the commissioning and the operation of the Data Acquisition (DAQ) and Experiment Control Systems (ECS) of the ALICE experiment at the CERN Large Hadron Collider (LHC). The DAQ and the ECS are the systems used respectively for the acquisition of all physics data and for the overall control of the experiment. They are two computing systems made of hundreds of PCs and data storage units interconnected via two networks. The collection of experimental data from the detectors is performed by several hundreds of high-speed optical links. We describe in detail the design considerations for these systems handling the extreme data throughput resulting from central lead ions collisions at LHC energy. The implementation of the resulting requirements into hardware (custom optical links and commercial computing equipment), infrastructure (racks, cooling, power distribution, control room), and software led to many innovative solutions which are described together with ...

  14. Music and Early Language Acquisition

    Science.gov (United States)

    Brandt, Anthony; Gebrian, Molly; Slevc, L. Robert

    2012-01-01

    Language is typically viewed as fundamental to human intelligence. Music, while recognized as a human universal, is often treated as an ancillary ability – one dependent on or derivative of language. In contrast, we argue that it is more productive from a developmental perspective to describe spoken language as a special type of music. A review of existing studies presents a compelling case that musical hearing and ability is essential to language acquisition. In addition, we challenge the prevailing view that music cognition matures more slowly than language and is more difficult; instead, we argue that music learning matches the speed and effort of language acquisition. We conclude that music merits a central place in our understanding of human development. PMID:22973254

  15. The acquisition of French in multilingual contexts

    CERN Document Server

    Guijarro-Fuentes, Pedro; Müller, Natascha

    2015-01-01

    This volume brings together new research from different theoretical paradigms addressing the acquisition of French as a second language. It focuses on the acquisition of French in combination with different languages and enriches our understanding of the particularities of French and the role of language combinations in the acquisition process.

  16. Managing IT Integration Risk in Acquisitions

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Kettinger, William J.

    2016-01-01

    The article discusses a framework for evaluating risk of information technology (IT) integration in acquisitions. Topics include the use of the experience of serial acquirer Trelleborg AB to show the merits of the framework for managing the risk and to determine low-risk acquisitions......, the importance of managing IT integration risk, and various risk areas for acquisition IT integration....

  17. Acquisition of HPLC-Mass Spectrometer

    Science.gov (United States)

    2015-08-18

    31-Jan-2015 Approved for Public Release; Distribution Unlimited Final Report: Acquisition of HPLC -Mass Spectrometer The views, opinions and/or findings...published in peer-reviewed journals: Final Report: Acquisition of HPLC -Mass Spectrometer Report Title The acquisition of the mass spectrometer has been a

  18. Reinventing the Platform Core Through Acquisition

    DEFF Research Database (Denmark)

    Toppenberg, Gustav; Henningsson, Stefan; Eaton, Ben

    2016-01-01

    the acquisition and integration of companies presenting innovative technologies of relevance to the platform core. Using a revelatory case study of Cisco Systems, we develop the explanatory notion of ‘coring acquisition’. In this type of acquisition value is created through the acquisition of companies...

  19. Studies in Filipino Second Language Acquisition.

    Science.gov (United States)

    Ramos, Teresita V.

    Very little research has been done on first or second language acquisition in the Philippines. Most second language learning studies cited in the literature concern acquisition of English in English-speaking communities, and most American studies of Filipino language acquisition are superficial, consisting primarily of morpheme analysis. The…

  20. Unmanned Maritime Systems Incremental Acquisition Approach

    Science.gov (United States)

    2016-12-01

    REPORT TYPE AND DATES COVERED MBA professional report 4. TITLE AND SUBTITLE UNMANNED MARITIME SYSTEMS INCREMENTAL ACQUISITION APPROACH 5. FUNDING...Approved for public release. Distribution is unlimited. UNMANNED MARITIME SYSTEMS INCREMENTAL ACQUISITION APPROACH Thomas Driscoll, Lieutenant...UNMANNED MARITIME SYSTEMS INCREMENTAL ACQUISITION APPROACH ABSTRACT The purpose of this MBA report is to explore and understand the issues

  1. Data Acquisition and Mass Storage

    Science.gov (United States)

    Vande Vyvre, P.

    2004-08-01

    The experiments performed at supercolliders will constitute a new challenge in several disciplines of High Energy Physics and Information Technology. This will definitely be the case for data acquisition and mass storage. The microelectronics, communication, and computing industries are maintaining an exponential increase of the performance of their products. The market of commodity products remains the largest and the most competitive market of technology products. This constitutes a strong incentive to use these commodity products extensively as components to build the data acquisition and computing infrastructures of the future generation of experiments. The present generation of experiments in Europe and in the US already constitutes an important step in this direction. The experience acquired in the design and the construction of the present experiments has to be complemented by a large R&D effort executed with good awareness of industry developments. The future experiments will also be expected to follow major trends of our present world: deliver physics results faster and become more and more visible and accessible. The present evolution of the technologies and the burgeoning of GRID projects indicate that these trends will be made possible. This paper includes a brief overview of the technologies currently used for the different tasks of the experimental data chain: data acquisition, selection, storage, processing, and analysis. The major trends of the computing and networking technologies are then indicated with particular attention paid to their influence on the future experiments. Finally, the vision of future data acquisition and processing systems and their promise for future supercolliders is presented.

  2. Aerial robotic data acquisition system

    International Nuclear Information System (INIS)

    Hofstetter, K.J.; Hayes, D.W.; Pendergast, M.M.

    1995-01-01

    A small unmanned aerial vehicle (UAV) equipped with sensors for physical and chemical measurements of remote environments, is described. A miniature helicopter airframe is used as a platform for sensor testing and development. The sensor output is integrated with the flight control system for real-time, interactive, data acquisition and analysis. Pre programmed flight missions will be flown with several sensors to demonstrate the cost-effective surveillance capabilities of this new technology. (author) 10 refs

  3. FACTORS INFLUENCING SECOND LANGUAGE ACQUISITION

    Directory of Open Access Journals (Sweden)

    Siti Khasinah

    2014-05-01

    Full Text Available Motivation, attitude, age, intelligence, aptitude, cognitive style, and personality are considered as factors that greatly influence someone in the process of his or her second language acquisition. Experts state that those factors give a more dominant contribution in SLA to learners variedly, depend on who the learners are, their age, how they behave toward the language, their cognitive ability, and also the way they learn.

  4. Modelling a data acquisition system

    International Nuclear Information System (INIS)

    Green, P.W.

    1986-01-01

    A data acquisition system to be run on a Data General ECLIPSE computer has been completely designed and developed using a VAX 11/780. This required that many of the features of the RDOS operating system be simulated on the VAX. Advantages and disadvantages of this approach are discussed, with particular regard to transportability of the system among different machines/operating systems, and the effect of the approach on various design decisions

  5. Information acquisition and financial intermediation

    OpenAIRE

    Boyarchenko, Nina

    2012-01-01

    This paper considers the problem of information acquisition in an intermediated market, where the specialists have access to superior technology for acquiring information. These informational advantages of specialists relative to households lead to disagreement between the two groups, changing the shape of the intermediation-constrained region of the economy and increasing the frequency of periods when the intermediation constraint binds. Acquiring the additional information is, however, cost...

  6. Behavior acquisition in artificial agents

    OpenAIRE

    Thurau, Christian

    2006-01-01

    Computational skill acquisition in robots and simulated agents has been a topic of increasing popularity throughout the last years. Despite impressive progress, autonomous behavior at a level of animals and humans are not yet replicated by machines. Especially when a complex environment demands versatile, goal-oriented behavior, current artificial systems show shortcomings. Consider for instance modern 3D computer games. Despite their key role for more emersive game experience, surprisingly l...

  7. Inductive acquisition of expert knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Muggleton, S.H.

    1986-01-01

    Expert systems divide neatly into two categories: those in which (1) the expert decisions result in changes to some external environment (control systems), and (2) the expert decisions merely seek to describe the environment (classification systems). Both the explanation of computer-based reasoning and the bottleneck (Feigenbaum, 1979) of knowledge acquisition are major issues in expert-systems research. The author contributed to these areas of research in two ways: 1. He implemented an expert-system shell, the Mugol environment, which facilitates knowledge acquisition by inductive inference and provides automatic explanation of run-time reasoning on demand. RuleMaster, a commercial version of this environment, was used to advantage industrially in the construction and testing of two large classification systems. 2. He investigated a new techniques called 'sequence induction' that can be used in construction of control systems. Sequence induction is based on theoretical work in grammatical learning. He improved existing grammatical learning algorithms as well as suggesting and theoretically characterizing new ones. These algorithms were successfully applied to acquisition of knowledge for a diverse set of control systems, including inductive construction of robot plans and chess end-gam strategies.

  8. Data Acquisition Backbone Core DABC

    International Nuclear Information System (INIS)

    Adamczewski, J; Essel, H G; Kurz, N; Linev, S

    2008-01-01

    For the new experiments at FAIR new concepts of data acquisition systems have to be developed like the distribution of self-triggered, time stamped data streams over high performance networks for event building. The Data Acquisition Backbone Core (DABC) is a software package currently under development for FAIR detector tests, readout components test, and data flow investigations. All kinds of data channels (front-end systems) are connected by program plug-ins into functional components of DABC like data input, combiner, scheduler, event builder, analysis and storage components. After detailed simulations real tests of event building over a switched network (InfiniBand clusters with up to 110 nodes) have been performed. With the DABC software more than 900 MByte/s input and output per node can be achieved meeting the most demanding requirements. The software is ready for the implementation of various test beds needed for the final design of data acquisition systems at FAIR. The development of key components is supported by the FutureDAQ project of the European Union (FP6 I3HP JRA1)

  9. Data acquisition for sensor systems

    CERN Document Server

    Taylor, H Rosemary

    1997-01-01

    'Data acquisition' is concerned with taking one or more analogue signals and converting them to digital form with sufficient accu­ racy and speed to be ready for processing by a computer. The increasing use of computers makes this an expanding field, and it is important that the conversion process is done correctly because information lost at this stage can never be regained, no matter how good the computation. The old saying - garbage in, garbage out - is very relevant to data acquisition, and so every part of the book contains a discussion of errors: where do they come from, how large are they, and what can be done to reduce them? The book aims to treat the data acquisition process in depth with less detailed chapters on the fundamental principles of measure­ ment, sensors and signal conditioning. There is also a chapter on software packages, which are becoming increasingly popular. This is such a rapidly changing topic that any review of available pro­ grams is bound to be out of date before the book re...

  10. Photovoltaic module parameters acquisition model

    Energy Technology Data Exchange (ETDEWEB)

    Cibira, Gabriel, E-mail: cibira@lm.uniza.sk; Koščová, Marcela, E-mail: mkoscova@lm.uniza.sk

    2014-09-01

    Highlights: • Photovoltaic five-parameter model is proposed using Matlab{sup ®} and Simulink. • The model acquisits input sparse data matrix from stigmatic measurement. • Computer simulations lead to continuous I–V and P–V characteristics. • Extrapolated I–V and P–V characteristics are in hand. • The model allows us to predict photovoltaics exploitation in different conditions. - Abstract: This paper presents basic procedures for photovoltaic (PV) module parameters acquisition using MATLAB and Simulink modelling. In first step, MATLAB and Simulink theoretical model are set to calculate I–V and P–V characteristics for PV module based on equivalent electrical circuit. Then, limited I–V data string is obtained from examined PV module using standard measurement equipment at standard irradiation and temperature conditions and stated into MATLAB data matrix as a reference model. Next, the theoretical model is optimized to keep-up with the reference model and to learn its basic parameters relations, over sparse data matrix. Finally, PV module parameters are deliverable for acquisition at different realistic irradiation, temperature conditions as well as series resistance. Besides of output power characteristics and efficiency calculation for PV module or system, proposed model validates computing statistical deviation compared to reference model.

  11. Future data acquisition at ISIS

    International Nuclear Information System (INIS)

    Pulford, W.C.A.; Quinton, S.P.H.; Johnson, M.W.; Norris, J.

    1989-01-01

    Over the past year ISIS beam intensity has increased steadily to 100 microamps during periods of good running. With the instrument users finding it comparatively easy to set up data-collection runs, we are facing an ever increasing volume of incoming data. Greatly improved detector technology, mainly involving large areas of zinc sulfide phosphor, are expected to contribute much to the capacity of new diffractometers as well as provide an enhancement path for many of the existing ones. It is clear that we are fast reaching the point where if we continue to use our current technology data collection techniques, our computer systems will no longer be able to migrate the data to long-term storage, let alone enable their analysis at a speed compatible with continuous use of the ISIS instruments. The most effect method to improve this situation is to reduce the volume of data flowing between the data acquisition electronics and the front end minicomputers, and to provide facilities to monitor data acquisition within the data acquisition electronics. Processing power must be incorporated closer to the point of data collection. Ways of doing this are discussed and evaluated. (author)

  12. Jefferson Lab's Distributed Data Acquisition

    International Nuclear Information System (INIS)

    Trent Allison; Thomas Powers

    2006-01-01

    Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) occasionally experiences fast intermittent beam instabilities that are difficult to isolate and result in downtime. The Distributed Data Acquisition (Dist DAQ) system is being developed to detect and quickly locate such instabilities. It will consist of multiple Ethernet based data acquisition chassis distributed throughout the seven-eights of a mile CEBAF site. Each chassis will monitor various control system signals that are only available locally and/or monitored by systems with small bandwidths that cannot identify fast transients. The chassis will collect data at rates up to 40 Msps in circular buffers that can be frozen and unrolled after an event trigger. These triggers will be derived from signals such as periodic timers or accelerator faults and be distributed via a custom fiber optic event trigger network. This triggering scheme will allow all the data acquisition chassis to be triggered simultaneously and provide a snapshot of relevant CEBAF control signals. The data will then be automatically analyzed for frequency content and transients to determine if and where instabilities exist

  13. Photovoltaic module parameters acquisition model

    International Nuclear Information System (INIS)

    Cibira, Gabriel; Koščová, Marcela

    2014-01-01

    Highlights: • Photovoltaic five-parameter model is proposed using Matlab ® and Simulink. • The model acquisits input sparse data matrix from stigmatic measurement. • Computer simulations lead to continuous I–V and P–V characteristics. • Extrapolated I–V and P–V characteristics are in hand. • The model allows us to predict photovoltaics exploitation in different conditions. - Abstract: This paper presents basic procedures for photovoltaic (PV) module parameters acquisition using MATLAB and Simulink modelling. In first step, MATLAB and Simulink theoretical model are set to calculate I–V and P–V characteristics for PV module based on equivalent electrical circuit. Then, limited I–V data string is obtained from examined PV module using standard measurement equipment at standard irradiation and temperature conditions and stated into MATLAB data matrix as a reference model. Next, the theoretical model is optimized to keep-up with the reference model and to learn its basic parameters relations, over sparse data matrix. Finally, PV module parameters are deliverable for acquisition at different realistic irradiation, temperature conditions as well as series resistance. Besides of output power characteristics and efficiency calculation for PV module or system, proposed model validates computing statistical deviation compared to reference model

  14. A CAMAC-based data acquisition system with a Macintosh interface

    International Nuclear Information System (INIS)

    McKisson, J.E.; Ely, D.W.; Weisenberger, A.G.; Piercy, R.B.; Haskins, P.S.

    1990-01-01

    This paper describes a commercially available Macintosh-based data acquisition system and its application to a specific measurement. Based on Computer Aided Measurement and Control (CAMAC) and Nuclear Instrumentation Module (NIM) standard modules, the data acquisition system features a hardware and software interface to a Macintosh computer. This system has been used both for laboratory and remote site measurements, and has been found to perform well as both a highly interactive laboratory system and as a very automatable system for long term data acquisition. Ease in configuration allows for flexibility in fast response applications where a data acquisition system is needed in short time. The system software also supports much of the data analysis and presentation of results with a versatile set of histogram display and manipulation tools. In a recent application, the system controlled data acquisition for two germanium detectors used as part of the whole- spacecraft induced activation measurements of the Long Duration Exposure Facility (LDEF) satellite

  15. A Mixed-Methods Approach to Investigating First- and Second-Language Incidental Vocabulary Acquisition through the Reading of Fiction

    Science.gov (United States)

    Reynolds, Barry Lee

    2015-01-01

    Adult English-L1 (n = 20) and English-L2 (n = 32) experimental groups were given a novel containing nonce words to read within two weeks to investigate whether the reading of fiction can induce a state of incidental vocabulary acquisition. After reading, an unexpected meaning recall translation assessment measuring acquisition of 49 target nonce…

  16. The MAST data acquisition upgrade

    International Nuclear Information System (INIS)

    McArdle, G.J.; Shibaev, Sergei; Storrs, John; Thomas-Davies, Nigel; Stephen, Robert

    2010-01-01

    A programme has begun on MAST to replace its ageing CAMAC and VME based data acquisition systems with new modern hardware which, together with several improvements in the supporting infrastructure, will provide support for faster data acquisition rates, longer-pulse operation, faster data access and higher reliability. The main principle of the upgrade was to use commercial off-the-shelf (COTS) hardware and well-established standards wherever possible. CompactPCI or PXI was chosen as the digitiser form factor to replace CAMAC/VME, and Ethernet would be used as the means to access all devices. The modular architecture of the MAST data acquisition software framework has helped to minimise the integration effort required to phase in new subsystems and/or new technologies whilst continuing to use the old hardware in other systems. The software framework was updated to allow more versatile use of the network-attached data acquisition devices. The new data acquisition devices had multiple connector types, which created difficulties with the cable interfacing. To resolve this and provide support for easy substitution, a standard connector interface was chosen, based on the most common connector type and pin-out already in use, and several cable assemblies were produced to connect the proprietary interface of the digitiser to the standard interface block. The in-house IDA-3 data storage format is unable to accommodate the larger file sizes and is increasingly difficult to maintain, so it is to be gradually phased out. The NetCDF-4/HDF5 data standard is being adopted as its replacement, thus reducing in-house maintenance whilst providing a data format that is more accessible to the Fusion community. Several other infrastructure upgrades were necessitated by the anticipated increase in data traffic and volume including the Central Timing System, the MAST Ethernet infrastructure and servers for front-end data processing, data storage and data access management. These

  17. Effect of telescope antenna diagram on the data acquisition in a stellar interferometer

    Science.gov (United States)

    Longueteau, Emmanuel; Delage, Laurent; Reynaud, François

    2017-11-01

    This paper deals with the effect of the telescope size on accuracy of the data acquisition in a optical fibre linked stellar interferometer. In this context we introduce the concept of antenna diagram commonly used for microwaves antennae. This concept is essential to explain the contrasts and the phaseclosure acquisitions corruption in a stellar interferometer. The telescope pointing errors induces additional effects that are superimposed with the field limitation and could become critical.

  18. Acquisition system for the CLIC Module

    CERN Document Server

    Vilalte, Sebastien

    2011-01-01

    The status of R&D activities for CLIC module acquisition are discussed [1]. LAPP is involved in the design of the local CLIC module acquisition crate, described in the document Study of the CLIC Module Front-End Acquisition and Evaluation Electronics [2]. This acquisition system is a project based on a local crate, assigned to the CLIC module, including several mother boards. These motherboards are foreseen to hold mezzanines dedicated to the different subsystems. This system has to work in radiation environment. LAPP is involved in the development of Drive Beam stripline position monitors read-out, described in the document Drive Beam Stripline BPM Electronics and Acquisition [3]. LAPP also develops a generic acquisition mezzanine that allows to perform all-around acquisition and components tests for drive beam stripline BPM read-out.

  19. Acquisitions by EMNCs in Developed Markets

    DEFF Research Database (Denmark)

    Rabbiosi, Larissa; Elia, Stefano; Bertoni, Fabio

    2012-01-01

    Building on an organisational learning perspective, we argue that emerging market firms’ international experience and home-country characteristics are core sources of learning. Furthermore, we argue that these factors constitute important determinants of emerging market firms’ acquisition behaviour...... in developed countries (south-north acquisitions). We test our hypotheses on a sample of 808 south-north acquisitions. The acquisitions were undertaken in Europe, Japan and North America (Canada and the US) between 1999 and 2008 by firms from the emerging economies of Brazil, Russia, India and China....... As suggested by the internationalisation process model, our results show that emerging market firms undertake acquisitions in developed countries in an incremental fashion. Acquisition experience in developed markets increases the likelihood of exploitative expansion, while acquisition experience in developing...

  20. Improving Acquisition Outcomes with Contextual Ambidexterity

    DEFF Research Database (Denmark)

    Meglio, Olimpia; King, David R.; Risberg, Annette

    2015-01-01

    The results of research on mergers and acquisitions often point to a need to improve acquisition outcomes and lessen the organizational turmoil that can often follow integration efforts. We assert that viewing acquisition integration through the lens of contextual ambidexterity may improve...... acquisition outcomes in two ways: by providing an integrated solution to the economic and social tensions in acquisitions, and by enabling managers to effectively confront the competing needs of task and human integration. We also posit that by building on contextual ambidexterity, we can extend...... the possibilities for both research and practice regarding task and human integration in acquisitions. We also emphasize the role of an integration manager and integration mechanisms in enabling contextual ambidexterity for successful acquisition integration. Finally, we identify implications for research...

  1. Ppr - Puma: a successful acquisition?

    OpenAIRE

    M. Buongiorno; B. Rovetta

    2010-01-01

    The PPR-Puma case explores the issue of evaluating the acquisition of Puma by the PPR group. Starting from the assessment of the business strategy and the analysis of the competitive scenario and firm-specific positioning, the case moves to a sound financial analysis and company valuation to be carried out with the objective to assess the actual value of the target company and the potential synergies to be achieved by the bidder. PPR is a very well-known player in the retail and luxury busine...

  2. Data acquisition system for SLD

    International Nuclear Information System (INIS)

    Sherden, D.J.

    1985-05-01

    This paper describes the data acquisition system planned for the SLD detector which is being constructed for use with the SLAC Linear Collider (SLC). An exclusively FASTBUS front-end system is used together with a VAX-based host system. While the volume of data transferred does not challenge the band-width capabilities of FASTBUS, extensive use is made of the parallel processing capabilities allowed by FASTBUS to reduce the data to a size which can be handled by the host system. The low repetition rate of the SLC allows a relatively simple software-based trigger. The principal components and overall architecture of the hardware and software are described

  3. Acquisition and extinction in autoshaping.

    Science.gov (United States)

    Kakade, Sham; Dayan, Peter

    2002-07-01

    C. R. Gallistel and J. Gibbon (2000) presented quantitative data on the speed with which animals acquire behavioral responses during autoshaping, together with a statistical model of learning intended to account for them. Although this model captures the form of the dependencies among critical variables, its detailed predictions are substantially at variance with the data. In the present article, further key data on the speed of acquisition are used to motivate an alternative model of learning, in which animals can be interpreted as paying different amounts of attention to stimuli according to estimates of their differential reliabilities as predictors.

  4. DEAP-3600 Data Acquisition System

    Science.gov (United States)

    Lindner, Thomas

    2015-12-01

    DEAP-3600 is a dark matter experiment using liquid argon to detect Weakly Interacting Massive Particles (WIMPs). The DEAP-3600 Data Acquisition (DAQ) has been built using a combination of commercial and custom electronics, organized using the MIDAS framework. The DAQ system needs to suppress a high rate of background events from 39Ar beta decays. This suppression is implemented using a combination of online firmware and software-based event filtering. We will report on progress commissioning the DAQ system, as well as the development of the web-based user interface.

  5. The GRIFFIN data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    Garnsworthy, A.B., E-mail: garns@triumf.ca [Physical Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3 (Canada); Pearson, C.J.; Bishop, D.; Shaw, B.; Smith, J.K.; Bowry, M. [Physical Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3 (Canada); Bildstein, V. [Department of Physics, University of Guelph, 50 Stone Rd E, Guelph, ON, Canada N1G 2W1 (Canada); Hackman, G. [Physical Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3 (Canada); Garrett, P.E. [Department of Physics, University of Guelph, 50 Stone Rd E, Guelph, ON, Canada N1G 2W1 (Canada); Linn, Y. [Physical Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3 (Canada); Martin, J.-P. [Department of Physics, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, QC, Canada H3T 1J4 (Canada); Mills, W.J. [Physical Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3 (Canada); Svensson, C.E. [Department of Physics, University of Guelph, 50 Stone Rd E, Guelph, ON, Canada N1G 2W1 (Canada)

    2017-05-01

    Gamma-Ray Infrastructure For Fundamental Investigations of Nuclei, GRIFFIN, is a new experimental facility for radioactive decay studies at the TRIUMF-ISAC laboratory. This article describes the details of the custom designed GRIFFIN digital data acquisition system. The features of the system that will enable high-precision half-life and branching ratio measurements with levels of uncertainty better than 0.05% are described. The system has demonstrated the ability to effectively collect signals from High-purity germanium crystals at counting rates up to 50 kHz while maintaining good energy resolution, detection efficiency and spectral quality.

  6. Profiling vocabulary acquisition in Irish.

    Science.gov (United States)

    O'Toole, Ciara; Fletcher, Paul

    2012-01-01

    Investigations into early vocabulary development, including the timing of the acquisition of nouns, verbs and closed-class words, have produced conflicting results, both within and across languages. Studying vocabulary development in Irish can contribute to this area, as it has potentially informative features such as a VSO word order, and semantically rich prepositions. This study used a parent report adapted for Irish, to measure vocabulary development longitudinally for children aged between 1,04 and 3,04. The findings indicated that the children learned closed-class words at relatively smaller vocabulary sizes compared to children acquiring other languages, and had a strong preference for nouns.

  7. Essays on mergers and acquisitions

    OpenAIRE

    Faelten, A.I.

    2016-01-01

    “Essays on Mergers and Acquisitions" tackles some of the most prominent business challenges related to M&A activity. The Introduction examines the reasons why deals fail through well-known case studies; Chapter 1 presents a new index measuring countries M&A maturity worldwide; Chapter 2 focus on the importance of corporate governance when conducting deals in unknown territories; whilst Chapter 3 and 4 conduct research on companies’ decision to tap capital markets and their subsequent M&A acti...

  8. Employment effects of foreign acquisition

    DEFF Research Database (Denmark)

    Bandick, Roger; Karpaty, Patrik

    2011-01-01

    This paper investigates the employment effects of foreign acquisitions in acquired firms in Swedish manufacturing during the 1990s; a period characterized by a dramatic increase in foreign ownership. We find some evidence of positive employment effects in acquired firms and it seems...... that the employment of skilled labor increasesmore than that of less-skilled labor. Our results indicate that the positive employment effects are more pronounced in acquired non-MNEs than in Swedish MNEs. Furthermore, we observe shifts in skill intensities toward higher shares of skilled labor in non-MNEs taken over...

  9. Software Switching for Data Acquisition

    CERN Multimedia

    CERN. Geneva; Malone, David

    2016-01-01

    In this talk we discuss the feasibility of replacing telecom-class routers with a topology of commodity servers acting as software switches in data acquisition. We extend the popular software switch, Open vSwitch, with a dedicated, throughput-oriented buffering mechanism. We compare the performance under heavy many-to-one congestion to typical Ethernet switches and evaluate the scalability when building larger topologies, exploiting the integration with software-defined networking technologies. Please note that David Malone will speak on behalf of Grzegorz Jereczek.

  10. Crystal ball data acquisition system

    International Nuclear Information System (INIS)

    Chestnut, R.; Kiesling, C.; Bloom, E.; Bulos, F.; Gaiser, J.; Godfrey, G.; Oreglia, M.; Partridge, R.; Peck, C.; Porter, F.; Aschman, D.; Cavali-Sforza, M.; Coyne, D.; Sadrozinski, H.; Kollmann, W.; Richardson, M.

    1979-01-01

    The data acquisition system for the Crystal Ball project at SLAC is described. A PDP-11/t55 using RSX-11M connected to the SLAC Triplex is the basis of the system. A ''physics pipeline'' allows physicists to write their own equipment-monitoring or physics tasks which require event sampling. As well, an interactive analysis package (MULTI) is in the pipeline. Histogram collection and display on the PDP are implemented using the Triplex histogramming package. Various interactive event displays are also implemented

  11. Virginia Power's capacity acquisition program

    International Nuclear Information System (INIS)

    Carney, R.W.

    1991-01-01

    Virginia Power is a utility with a growing demand for electricity. To meet that growth it has embarked on an aggressive program to encourage the construction of privately-owned generating plants. In 1988 it conducted the largest competitive acquisition program by any utility to date. Virginia Power has retained the option to build plants if the bids it receives are too costly or do not meet the needs of its customers. This paper describes the situation at Virginia Power, the program it has implemented, and the capacity additions which are scheduled between 1989 and 1995

  12. Mergers and Acquisitions in India

    OpenAIRE

    Agarwal, Ankita

    2009-01-01

    From the past few decades, Mergers and Acquisitions (M&A) have dominated the environment in which the companies operate. Whenever there is an announcement about a merger, there is an excitement and expectation among the shareholders. This expectation may or may not convert into an abnormal return. It is useful to have some kind of research activity on the performance of M&A, as both bidders and target firms will gain from it. The results have revealed that on average, the returns to the targ...

  13. Future data acquisition at ISIS

    International Nuclear Information System (INIS)

    Pulford, W.C.A.; Quinton, S.P.H.; Johnson, M.W.; Norris, J.

    1989-01-01

    Data collection techniques at ISIS are fast reaching the point where the current computer systems will no longer be able to migrate the data to long-term storage, let alone enable their analysis at a speed compatible with continuous use of the ISIS instruments. The current data acquisition electronics (DAE 1) and migration path work effectively but have a number of inherent difficulties: (1) Seven instruments are equipped with VAX computers as their Front End Minicomputers (FEM). Unfortunately these machines usually possess insufficient processor power to perform some of the more complex data reduction. This means that the raw data have necessarily to be networked to the HUB computer before analysis. (2) The size of bulk store memory is restricted to 16 Mbytes by the 24 bit address field of Multibus. (3) The DAE error detection and analysis system of FEM is crude. It is clear that the most effective method to improve on this situation is to reduce the data volume flowing between the DAE and the FEM and to provide facilities to monitor data acquisition within the DAE. For these purposes processing power must be incorporated closer to the point of data collection. It has been decided to implement processing elements within DAE 2 (the next generation of DAE) in the form of intelligent memory boards. 6 figs., 1 tab

  14. The acquisition of conditioned responding.

    Science.gov (United States)

    Harris, Justin A

    2011-04-01

    This report analyzes the acquisition of conditioned responses in rats trained in a magazine approach paradigm. Following the suggestion by Gallistel, Fairhurst, and Balsam (2004), Weibull functions were fitted to the trial-by-trial response rates of individual rats. These showed that the emergence of responding was often delayed, after which the response rate would increase relatively gradually across trials. The fit of the Weibull function to the behavioral data of each rat was equaled by that of a cumulative exponential function incorporating a response threshold. Thus, the growth in conditioning strength on each trial can be modeled by the derivative of the exponential--a difference term of the form used in many models of associative learning (e.g., Rescorla & Wagner, 1972). Further analyses, comparing the acquisition of responding with a continuously reinforced stimulus (CRf) and a partially reinforced stimulus (PRf), provided further evidence in support of the difference term. In conclusion, the results are consistent with conventional models that describe learning as the growth of associative strength, incremented on each trial by an error-correction process.

  15. DUMAND data acquisition with triggering

    International Nuclear Information System (INIS)

    Brenner, A.E.; Theriot, D.; March, R.H.

    1980-01-01

    A data acquisition scheme for the standard DUMAND array that includes a simple triggering scheme as a fundamental part of the system is presented. Although there are a number of not yet fully understood parameters, it is assumed that thresholds can be set in such a manner as to give rise to a triggered signal that is not so dominated by randoms that it gives a substantial decrease in the data acquisition rate over that which would be required by a nontriggered system. It is also assumed that the triggering logic is relatively simple and does not need major computational capabilities for a trigger logic decision. With these assumptions, it is possible to generate the trigger at the array and restrict the data transfer to shore. However, with a not unreasonable delay of 200 microseconds, it is even possible to transmit the information for the trigger to shore and perform all that logic on the shore. The critical point is to send the minimum amount of information necessary to construct the trigger such that one need not send all the possible information in all detectors of the array continuously to shore. 1 figure

  16. The ALICE data acquisition system

    Energy Technology Data Exchange (ETDEWEB)

    Carena, F.; Carena, W.; Chapeland, S.; Chibante Barroso, V.; Costa, F. [European Organization for Nuclear Research (CERN), Geneva 23 (Switzerland); Dénes, E. [Research Institute for Particle and Nuclear Physics, Wigner Research Center, Budapest (Hungary); Divià, R.; Fuchs, U. [European Organization for Nuclear Research (CERN), Geneva 23 (Switzerland); Grigore, A. [European Organization for Nuclear Research (CERN), Geneva 23 (Switzerland); Politehnica Univesity of Bucharest, Bucharest (Romania); Kiss, T. [Cerntech Ltd., Budapest (Hungary); Simonetti, G. [Dipartimento Interateneo di Fisica ‘M. Merlin’, Bari (Italy); Soós, C.; Telesca, A.; Vande Vyvre, P. [European Organization for Nuclear Research (CERN), Geneva 23 (Switzerland); Haller, B. von, E-mail: bvonhall@cern.ch [European Organization for Nuclear Research (CERN), Geneva 23 (Switzerland)

    2014-03-21

    In this paper we describe the design, the construction, the commissioning and the operation of the Data Acquisition (DAQ) and Experiment Control Systems (ECS) of the ALICE experiment at the CERN Large Hadron Collider (LHC). The DAQ and the ECS are the systems used respectively for the acquisition of all physics data and for the overall control of the experiment. They are two computing systems made of hundreds of PCs and data storage units interconnected via two networks. The collection of experimental data from the detectors is performed by several hundreds of high-speed optical links. We describe in detail the design considerations for these systems handling the extreme data throughput resulting from central lead ions collisions at LHC energy. The implementation of the resulting requirements into hardware (custom optical links and commercial computing equipment), infrastructure (racks, cooling, power distribution, control room), and software led to many innovative solutions which are described together with a presentation of all the major components of the systems, as currently realized. We also report on the performance achieved during the first period of data taking (from 2009 to 2013) often exceeding those specified in the DAQ Technical Design Report.

  17. Data acquisition system for MEGHA

    International Nuclear Information System (INIS)

    Chappell, S.P.G.; Hunt, R.A.; Smith, D.; Rae, W.D.M.; Clarke, N.M.; Freer, M.; Fulton, B.R.; Jagpal, S.S.; Singer, S.M.; Watson, D.L.

    2000-01-01

    A multi-channel data acquisition system has been commissioned for the Charissa 'MEGHA' detector array. It is designed to read multiparameter events where there are many potential channels (320) but where only a fraction of these are active in any typical event. Custom-built pre- and main amplifiers process the amplitude (energy) signal from each detector and the system records both amplitude and time of arrival for each signal within an event. The signal amplitude is converted to time using the standard Wilkinson technique and then combined with its time of arrival into a single time trace. These traces are converted by multi-hit TDCs, which only convert the active channels and thus reduce the processing load. Additional custom-built CAMAC modules organise the TDC output into a suitable form for storage and transmission to a network of processor terminals over standard ethernet. This paper presents a description of the data acquisition system from preamplifier through to final storage in a VME-based system and subsequent distribution to a network of Sun terminals over ethernet. The system performance is illustrated with results from heavy-ion elastic scattering recorded with position sensitive strip detectors

  18. Acquisitions in the Electricity Sector: Active vs. Passive Owners

    Energy Technology Data Exchange (ETDEWEB)

    Nese, Gjermund

    2002-07-01

    The starting point of this paper is a mixed oligopoly market consisting of n privately owned profit maximizing firms and 1 state-owned welfare maximizing firm. Motivated by the trend of mergers and acquisitions in the liberalized electricity markets, and by the debate about public or private ownership, the paper looks at two cases. In Case 1, the state-owned company acquires an ownership share in one of the private companies. In Case 2, the state-owned company is partially privatised. The paper focuses on differences in generated quantities and social surplus, depending on whether the investors behind the acquisitions are behaving as active or passive owners. One result shows that in the case of partial privatization, passive ownership provides the highest total industry generation, while active ownership induces maximum social surplus. (author)

  19. Acquisitions in the Electricity Sector: Active vs. Passive Owners

    International Nuclear Information System (INIS)

    Nese, Gjermund

    2002-01-01

    The starting point of this paper is a mixed oligopoly market consisting of n privately owned profit maximizing firms and 1 state-owned welfare maximizing firm. Motivated by the trend of mergers and acquisitions in the liberalized electricity markets, and by the debate about public or private ownership, the paper looks at two cases. In Case 1, the state-owned company acquires an ownership share in one of the private companies. In Case 2, the state-owned company is partially privatised. The paper focuses on differences in generated quantities and social surplus, depending on whether the investors behind the acquisitions are behaving as active or passive owners. One result shows that in the case of partial privatization, passive ownership provides the highest total industry generation, while active ownership induces maximum social surplus. (author)

  20. Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs).

    Science.gov (United States)

    Wang, Li; Zhang, Yi; Wang, Weiguo; Zhu, Yunjie; Chen, Yang; Tian, Bole

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3'-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53

  1. Multi spectral scaling data acquisition system

    International Nuclear Information System (INIS)

    Behere, Anita; Patil, R.D.; Ghodgaonkar, M.D.; Gopalakrishnan, K.R.

    1997-01-01

    In nuclear spectroscopy applications, it is often desired to acquire data at high rate with high resolution. With the availability of low cost computers, it is possible to make a powerful data acquisition system with minimum hardware and software development, by designing a PC plug-in acquisition board. But in using the PC processor for data acquisition, the PC can not be used as a multitasking node. Keeping this in view, PC plug-in acquisition boards with on-board processor find tremendous applications. Transputer based data acquisition board has been designed which can be configured as a high count rate pulse height MCA or as a Multi Spectral Scaler. Multi Spectral Scaling (MSS) is a new technique, in which multiple spectra are acquired in small time frames and are then analyzed. This paper describes the details of this multi spectral scaling data acquisition system. 2 figs

  2. Disclosure requirements for merger and acquisition transactions

    International Nuclear Information System (INIS)

    Holm, D.I.

    1998-01-01

    The legal disclosure requirements for merger and acquisition transactions involving Canadian public companies are described. The focus is on issues regarding merger and acquisition related disclosure, including the potential consequences of failing to provide proper information, Ontario Securities Commission Policy 9.1 considerations regarding valuation, review, and approval, cross border considerations and financing a merger and acquisition transaction. Legal and practical consequences for failing to provide proper disclosure, including the steps involved in establishing the due diligence defence, are also discussed

  3. Software for a multichannel acquisition card

    International Nuclear Information System (INIS)

    Arista Romeu, E. J.; Diaz Garcia, A.; Vela Morales, O.

    2013-01-01

    A software developed in C++ for a multichannel acquisition card is presented. The use of an acquisition add-on card with multiple channels is a suitable solution to substitute several instruments, allowing simultaneous acquisition with each channel. In this work, the limitations of a concrete hardware are discussed and also several different approaches have been suggested. Some preliminary results obtained in laboratory conditions are shown. (Author)

  4. Determinants of Bank Acquisitions in ASEAN

    OpenAIRE

    Ng, Seok Lee

    2013-01-01

    A considerable number of acquisitions have taken place in the ASEAN banking industry from the 1997 Asian financial crisis onwards. The trend raises the question as to what ex-ante factors motivate the involvement of banks in acquisitions, as existing literature indicates inconclusive benefits from M&As. As such, the study examines the determinants of acquisitions for 47 acquired banks and 33 acquiring banks in ASEAN from 2003 to 2011. Three logistic regressions are employed to identify the ba...

  5. Mergers and acquisitions: valuation and risk assessment

    International Nuclear Information System (INIS)

    McVeigh, C.A.

    1996-01-01

    An overview of various aspects of mergers and acquisition transactions in the petroleum industry were presented. Incentives to mergers and acquisitions were reviewed and discussed, among them value opportunity, critical size, incremental tax pools, financial distress, shareholder dissatisfaction, strategic infrastructure position, complementary assets, and undeveloped land inventory. Current trends in mergers and acquisitions were highlighted. An industry checklist for risk assessments discussing financial position, engineering forecasts, and taxation was also included

  6. A Conceptual Model for Urgent Acquisition Programs

    Science.gov (United States)

    2017-04-06

    traditional acquisition to get things done quicker remaining a constant. “Recognizing this reality is the first step in building an acquisition system...an Operational Needs Statement or Joint Urgent Operational Needs Statement. Urgent acquisition policy focuses on getting capability to the field...typically funded for the equipping effort, which does not include funding for things like Service-wide production, training, or sustainment. In an AROC

  7. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    International Nuclear Information System (INIS)

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng; Xia, Qiang

    2012-01-01

    Highlights: ► miR-199a-5p levels were significantly decreased after cisplatin treatment. ► Cisplatin treatment induced autophagy activation. ► Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  8. Evaluation of the Acquisition Audit Process

    National Research Council Canada - National Science Library

    Smolenyak, Barbara

    1997-01-01

    The objectives were to evaluate the efficiency and effectiveness of the acquisition audit process, determine whether reductions can be achieved by improvements in prioritizing audits, and determine...

  9. Acquisition in different and special subject areas

    CERN Document Server

    Katz, Linda S

    2013-01-01

    Learn how acquisitions librarians successfully serve specialized users! In this book, you'll find profiles, methods, and processes for acquisitions in specialized subject areas, such as local and regional poetry, oceanography, educational information in electronic formats, popular fiction, regional and ethnic materials, and more. Seasoned acquisitions librarians share their experiences in gathering the hard-to-find materials their libraries' highly specialized clients need to access. You'll also examine issues surrounding the acquisition of new reference tools that are vital in today's emergi

  10. Validating Acquisition IS Integration Readiness with Drills

    DEFF Research Database (Denmark)

    Wynne, Peter J.

    2017-01-01

    To companies, mergers and acquisitions are important strategic tools, yet they often fail to deliver their expected value. Studies have shown the integration of information systems is a significant roadblock to the realisation of acquisition benefits, and for an IT department to be ready......), to understand how an IT department can use them to validate their integration plans. The paper presents a case study of two drills used to validate an IT department’s readiness to carry out acquisition IS integration, and suggests seven acquisition IS integration drill characteristics others could utilise when...

  11. Emerging Market Firms’ Acquisitions in Advanced Markets

    DEFF Research Database (Denmark)

    Stucchi, Tamara

    2012-01-01

    markets. These antecedents can influence emerging market firms’ capacities to absorb or exploit technological and/or marketing advantages in advanced markets. In order to be successful, emerging market firms have to undertake those upmarket acquisitions that best “fit” their antecedents. Four mutually......This study draws upon the resource-based view and the institution-based view of the firm to provide a comprehensive overview of how different resource-, institution- and industry-based antecedents affect the motivations guiding the acquisitions that emerging market firms undertake in advanced...... exclusive acquisition strategies are derived, which are then illustrated using examples of Indian firms’ acquisitions in advanced markets....

  12. Electric vehicle data acquisition system

    DEFF Research Database (Denmark)

    Svendsen, Mathias; Winther-Jensen, Mads; Pedersen, Anders Bro

    2014-01-01

    and industrial applications, e.g. research in electric vehicle driving patterns, vehicle substitutability analysis and fleet management. The platform is based on a embedded computer running Linux, and features a high level of modularity and flexibility. The system operates independently of the make of the car......, by using the On-board Diagnostic port to identify car model and adapt its software accordingly. By utilizing on-board Global Navigation Satellite System, General Packet Radio Service, accelerometer, gyroscope and magnetometer, the system not only provides valuable data for research in the field of electric......A data acquisition system for electric vehicles is presented. The system connects to the On-board Diagnostic port of newer vehicles, and utilizes the in-vehicle sensor network, as well as auxiliary sensors, to gather data. Data is transmitted continuously to a central database for academic...

  13. Modelling of data acquisition systems

    International Nuclear Information System (INIS)

    Buono, S.; Gaponenko, I.; Jones, R.; Mapelli, L.; Mornacchi, G.; Prigent, D.; Sanchez-Corral, E.; Spiwoks, R.; Skiadelli, M.; Ambrosini, G.

    1994-01-01

    The RD13 project was approved in April 1991 for the development of a scalable data taking system suitable to host various LHC studies. One of its goals is to use simulations as a tool for understanding, evaluating, and constructing different configurations of such data acquisition (DAQ) systems. The RD13 project has developed a modelling framework for this purpose. It is based on MODSIM II, an object-oriented, discrete-event simulation language. A library of DAQ components allows to describe a variety of DAQ architectures and different hardware options in a modular and scalable way. A graphical user interface (GUI) is used to do easy configuration, initialization and on-line monitoring of the simulation program. A tracing facility is used to do flexible off-line analysis of a trace file written at run-time

  14. Data acquisition and control network

    International Nuclear Information System (INIS)

    Hajjar, Victor.

    1983-02-01

    We have participated in the construction of the CELLO detector on the PETRA e + e - Collider in Hamburg in order to test some of the current high energy physics theories. Some 60.000 channels collecting the detector informations are connected to the main computer through the CAMAC acquisition system and specialized ROMULUS subsystems. Each of these subsystems is monitored by its dedicated microprocessor using a CAMAC dataway spy module. All these microprocessors are connected to the main computer through a ''STAR'' type network. Data are read out by the main computer (PDP11-45) and concentrated in a circular type buffer. They are then filtered and transfered to a PDP11-55, also in the network, for storing [fr

  15. Knowledge acquisition for temporal abstraction.

    Science.gov (United States)

    Stein, A; Musen, M A; Shahar, Y

    1996-01-01

    Temporal abstraction is the task of detecting relevant patterns in data over time. The knowledge-based temporal-abstraction method uses knowledge about a clinical domain's contexts, external events, and parameters to create meaningful interval-based abstractions from raw time-stamped clinical data. In this paper, we describe the acquisition and maintenance of domain-specific temporal-abstraction knowledge. Using the PROTEGE-II framework, we have designed a graphical tool for acquiring temporal knowledge directly from expert physicians, maintaining the knowledge in a sharable form, and converting the knowledge into a suitable format for use by an appropriate problem-solving method. In initial tests, the tool offered significant gains in our ability to rapidly acquire temporal knowledge and to use that knowledge to perform automated temporal reasoning.

  16. Data acquisition, reconstruction, and display

    International Nuclear Information System (INIS)

    Huesman, R.H.

    1981-01-01

    A special emphasis of the Research Medicine program is the development of methods for acquiring and manipulating data from the Donner 280-crystal positron emission tomograph. This past year, development of a system capable of taking 1 million events per second while simultaneously correcting for unwanted accidental coincidence events was completed. The system permits the simultaneous acquisition of data for eight different time-slices of the cardiac cycle. A microprocessor responds to the patient's electrocardiogram (EKG) signal, routing data to the histogram memory corresponding to the phase of the cardiac cycle indicated by the signal. Additional work completed this year includes quantitation of the signal-to-noise ratio to be expected when imaging the human head. Effort is continuing on the more complicated problem of noise propagation in reconstructions of the human thorax

  17. 76 FR 68044 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-54; Small Entity Compliance Guide

    Science.gov (United States)

    2011-11-02

    ... Acquisition Circular 2005-54; Small Entity Compliance Guide AGENCY: Department of Defense (DoD), General... Federal Acquisition Circular (FAC) 2005-54, which amend the Federal Acquisition Regulation (FAR... (FAR Case 2009-006) This final rule amends the FAR to implement Executive Order (E.O.) 13494, Economy...

  18. 75 FR 19179 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-41; Small Entity Compliance Guide

    Science.gov (United States)

    2010-04-13

    ... Acquisition Circular 2005-41; Small Entity Compliance Guide AGENCIES: Department of Defense (DoD), General... Federal Acquisition Circular (FAC) 2005-41 which amends the Federal Acquisition Regulation (FAR... projects where the total cost to the Government is $25 million or more in order to promote economy and...

  19. 75 FR 54524 - Defense Federal Acquisition Regulation Supplement; Acquisition Strategies To Ensure Competition...

    Science.gov (United States)

    2010-09-08

    ...., because the changes are to internal Government organization and operating procedures only. The rule... 48 CFR Part 207 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations... Life Cycle of Major Defense Acquisition Programs (DFARS Case 2009-D014) AGENCY: Defense Acquisition...

  20. 48 CFR 7.402 - Acquisition methods.

    Science.gov (United States)

    2010-10-01

    ... ACQUISITION PLANNING Equipment Lease or Purchase 7.402 Acquisition methods. (a) Purchase method. (1) Generally, the purchase method is appropriate if the equipment will be used beyond the point in time when cumulative leasing costs exceed the purchase costs. (2) Agencies should not rule out the purchase method of...

  1. Distributed multiprotocol acquisition network for environmental data

    Science.gov (United States)

    Barone, Fabrizio; De Rosa, Rosario; Milano, Leopoldo; Qipiani, Ketevan

    2003-03-01

    The acquisition and storage of large amount of data coming from distributed environmental sensors of different kind can be solved with the aid of a network between the acquisition subsystems, but problems can arise if they are not homogeneous. In this case the network should be as flexible as possible to ensure modularity and connectivity. In this work we describe the development and testing of a network based acquisition system. The network uses, where possible, commercial products, based on different standards, in order to increase the availability of its components, as well as its modularity. In addition it is completely independent from proprietary hardware and software products. In particular we tested an acquisition network based on multiple transmission protocol, like wireless and cabled RS232 and Fast Ethernet, which includes the acquisition, archiving and data analysis systems. Each acquisition subsystem can get time from satellite using GPS, and is able to monitor seismic activity, temperature, pressure, humidity and electromagnetic data. The sampling frequency and the dynamics of the acquired data can be matched to the characteristics of each probe. All the acquisition stations can use different platform as well as different operating systems. Tests have been performed to evaluate the capability of long acquisition periods and the fault tolerance of the whole system.

  2. Acquisitions and Real Options : The Greenfield Alternative

    NARCIS (Netherlands)

    Brouthers, Keith D.; Dikova, Desislava

    P>Although acquisitions are a popular way to enter new markets, empirical evidence tends to indicate few benefits accrue to acquiring firms. This might be the case because firms use acquisitions when they should be employing an alternative mode of expansion. Applying real options theory to this

  3. Data-Acquisition Systems for Fusion Devices

    NARCIS (Netherlands)

    van Haren, P. C.; Oomens, N. A.

    1993-01-01

    During the last two decades, computerized data acquisition systems (DASs) have been applied at magnetic confinement fusion devices. Present-day data acquisition is done by means of distributed computer systems and transient recorders in CAMAC systems. The development of DASs has been technology

  4. OPAL: selection and acquisition of LEP data

    International Nuclear Information System (INIS)

    Le Du, P.

    1985-01-01

    The OPAL project (Omni Purpose aparatus for LEP) is presented. It will be a frame and an example to explain the main problems and limitations concerning the mode of event selection, acquisition and information transfer to the final registering system. A quick review of the different problems related to data selection and acquisition is made [fr

  5. Input and Intake in Language Acquisition

    Science.gov (United States)

    Gagliardi, Ann C.

    2012-01-01

    This dissertation presents an approach for a productive way forward in the study of language acquisition, sealing the rift between claims of an innate linguistic hypothesis space and powerful domain general statistical inference. This approach breaks language acquisition into its component parts, distinguishing the input in the environment from…

  6. Child Language Acquisition: Contrasting Theoretical Approaches

    Science.gov (United States)

    Ambridge, Ben; Lieven, Elena V. M.

    2011-01-01

    Is children's language acquisition based on innate linguistic structures or built from cognitive and communicative skills? This book summarises the major theoretical debates in all of the core domains of child language acquisition research (phonology, word-learning, inflectional morphology, syntax and binding) and includes a complete introduction…

  7. Foreign acquisition, plant survival, and employment growth

    DEFF Research Database (Denmark)

    Bandick, Roger; Görg, Holger

    2010-01-01

    This paper analyzes the effect of foreign acquisition on survival and employment growth of targets using data on Swedish manufacturing plants.We separate targeted plants into those within Swedish MNEs, Swedish exporting non-MNEs, and purely domestic firms. The results, controlling for possible...... acquisitions. We find robust positive employment growth effects only for exporters and only if the takeover is vertical....

  8. Data Acquisition System On Beta Installation

    International Nuclear Information System (INIS)

    Abtokhi, Ahmad; Nurhanan; Sudarno; Sumarno, Edy

    2000-01-01

    Data acquisition system is needed on every installation. This is important used to monitoring and processing data to get information desired. This system applied to β installation which is facility to carry out experiments on accident condition like as reflooding phenomena in test section. The 16 exp.th channel data acquisition system is drived by ADC 0804 and programme application DELPHI

  9. EBT data acquisition and analysis system

    International Nuclear Information System (INIS)

    Burris, R.D.; Greenwood, D.E.; Stanton, J.S.; Geoffroy, K.A.

    1980-10-01

    This document describes the design and implementation of a data acquisition and analysis system for the EBT fusion experiment. The system includes data acquisition on five computers, automatic transmission of that data to a large, central data base, and a powerful data retrieval system. The system is flexible and easy to use, and it provides a fully documented record of the experiments

  10. Acquired Inventors’ Productivity after Horizontal Acquisition

    DEFF Research Database (Denmark)

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    Effective integration of the R&D functions of the acquired and acquiring firms is essential for knowledge recombination after acquisition. However, prior research suggests that the post-acquisition integration process often damages the inventive labor force. We argue that an examination of the mu...

  11. 23 CFR 710.501 - Early acquisition.

    Science.gov (United States)

    2010-04-01

    ... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Property Acquisition Alternatives § 710.501 Early acquisition. (a) Real property... the Civil Rights Act of 1964 (42 U.S.C. 2000d-2000d-4); (5) The State determined and the FHWA concurs...

  12. 23 CFR 710.309 - Acquisition.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Acquisition. 710.309 Section 710.309 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT RIGHT-OF-WAY AND REAL ESTATE Project Development § 710.309 Acquisition. The process of acquiring real property includes...

  13. Data Acquisition and Real-Time Systems.

    Science.gov (United States)

    Lawrence, D. E., Ed.; Fenwick, P. M., Ed.

    The first group of papers starts with a tutorial paper which surveys the methods used in data acquisition systems. Other papers in this group describe: (1) some problems involved in the computer acquisition of high-speed randomly-occurring data and the protection of this data from accidental corruption, (2) an input/output bus to allow an IBM…

  14. Consumption Skill Acquisition in Ski Schools

    DEFF Research Database (Denmark)

    Woermann, Niklas; Wieser, Verena

    2016-01-01

    Remedying the absence of a cultural theory of consumption skill acquisition, we use video data to explore how consumers learn in ski schools. We identify six modes of skill acquisition and theorize the interplay between the sensori-motor system, the conscious state of skillful coping...

  15. Acquisition-based Dynamic Reconfiguration Capabilities

    NARCIS (Netherlands)

    Amiryany Araghy, N.; Huysman, M.H.; de Man, A.P.; Cloodt, M.; Demetriss, V.; Weber, Y.; Kaufmann, R.; Tarba, S.

    2009-01-01

    The success of knowledge acquisitions is dependent upon firm’s ability to integrate knowledge-based resources and thus share knowledge, in order to innovate. Regardless of the increasing number of knowledge acquisitions, however, an understanding of how successful firms direct their knowledge

  16. 77 FR 59339 - Acquisition of Commercial Items

    Science.gov (United States)

    2012-09-27

    ... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 212 Acquisition of Commercial Items CFR Correction 212.504 [Corrected] In Title 48 of the Code of Federal Regulations, Chapter 2 (Parts 201--299), revised as of October 1, 2011, on page 73, in section 212.504, paragraph (a) is...

  17. Conference data acquisition process at CERN

    CERN Multimedia

    CERN. Geneva

    2002-01-01

    Will describe the data acquisition process set up at CERN (and tools developed for this purpose) and propose a MaC capture module based on CERN's experience. Will also focus on the video acquisition and how we can improve it to produce better InDiCo analysis test videos.

  18. Maximizing remanufacturing profit using product acquisition management

    NARCIS (Netherlands)

    V.D.R. Guide Jr (Daniel); R.H. Teunter (Ruud); L.N. van Wassenhove (Luk)

    2001-01-01

    textabstractThe profitability of remanufacturing depends on the quantity and quality of product returns and on the demand for remanufactured products. The quantity and quality of product returns can be influenced by varying quality dependent acquisition prices, i.e., by using product acquisition

  19. Data acquisition in nuclear and particle physics

    International Nuclear Information System (INIS)

    Renk, B.

    1993-01-01

    An introduction to the methodics of the measurement data acquisition in nuclear and particle physics for students of physics as well as experimental physicists and engineers in research and industry. The contents are: Obtaining of measurement data, digitizing and triggers, memories and microprocessors, bus systems, communication and networks, and examples for data acquisition systems

  20. The Chateau de Cristal data acquisition system

    International Nuclear Information System (INIS)

    Villard, M.M.

    1987-05-01

    This data acquisition system is built on several dedicated data transfer busses: ADC data readout through the FERA bus, parallel data processing in two VME crates. High data rates and selectivities are performed via this acquisition structure and new developed processing units. The system modularity allows various experiments with additional detectors

  1. 78 FR 35195 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-06-12

    ... DEPARTMENT OF ENERGY 48 CFR Parts 925, 952, and 970 RIN 1991-AB99 Acquisition Regulations: Export... Energy (DOE) is proposing to amend the Department of Energy Acquisition Regulation (DEAR) to add export... comments, identified by ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods...

  2. 78 FR 45168 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-07-26

    ... DEPARTMENT OF ENERGY 48 CFR Parts 925, 952 and 970 RIN 1991-AB99 Acquisition Regulations: Export... (78 FR 35195) to amend the Department of Energy Acquisition Regulation (DEAR) to add export control... ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods: Federal eRulemaking Portal...

  3. Acquisition of reactor experimental data; Akviziter reaktorskih eksperimentalnih podataka

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, M; Tasic, A [Institut za nuklearne nauke ' Boris Kidric' , Vinca, Belgrade (Yugoslavia)

    1966-07-01

    This paper include the analysis of possible experiments and relevant experimental devices for detection, registering and analysis of inducing and response signals. It contains a concept of our system for detection and registering of data, which i appropriate for our research program. Non-typical details of certain acquisition systems are described as well. U ovom radu se analiziraju moguci eksperimenti i odgovarajuci eksperimentalni uredjaji za detekciju, registraciju i analizu signala pobude i odziva. Dalje se iznosi koncepcija naseg sistema za detekciju i registraciju podataka pogodnog za nas program istrazivanja. Netipicni detalji pojedinih kola akvizitera takodje se iznose u radu (author)

  4. Merging Platform Ecosystems in Technology Acquisitions

    DEFF Research Database (Denmark)

    Dowie, Jamie; Henningsson, Stefan; Kude, Thomas

    2017-01-01

    of the merging companies. Given the increasing importance of platforms and value co-creation with third-party providers for companies making technology acquisitions, we complement existing literature by reframing the analysis of technology acquisitions to include the merger of the broader partner ecosystems....... Specifically, we draw on theories of ecosystem governance to analyze how ecosystem tensions unfolded during the ecosystem merger and how the acquirer governed these tensions in SAP SE’s acquisition of the e-commerce provider Hybris AG. Our findings suggest that the governance of ecosystem tensions...... is an important aspect of managing technology acquisitions. We identify the pre-acquisition relation between the acquired company’s ecosystem partners and the acquirer as an important context factor for explaining how a partner company is exposed to the ecosystem tensions during the merger....

  5. IT Consultants in Acquisition IT Integration

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Øhrgaard, Christian

    2016-01-01

    strategic IT initiatives and how companies can draw effectively on their services. The paper investigates the use of consultants in relation to one type of major strategic IT initiative: acquisition IT integration. Acquisition IT integration, which is the integration of the acquirer’s and target......’s IT following a corporate acquisition, presents a difficult but crucial IT challenge for the many acquiring organizations. Through a comparative case study of four acquirers, theoretically grounded in the resource-based view of the firm, it is analyzed how acquirers draw on external consultants to realize...... acquisition IT integration. Two complementary and two supplementary roles consultants assume in these projects are identified. Additionally, three characteristics of the acquisition IT integration strategy are identified that influence how the acquirers assign different roles to IT consultants. The resulting...

  6. Risks of Mergers and Acquisitions Processes

    Directory of Open Access Journals (Sweden)

    Skitsko Volodymyr I.

    2017-06-01

    Full Text Available Despite structural changes both in the economies of individual countries and in the world at large, the size of the merger/acquisition market is not declining and is tending to grow further. However, uncertainty in the global environment increases the importance of proper analysis, assessment and risk management in merger/acquisition transactions. Using the relevant research and publications by various authors, we have built a general ranking of the significance of merger and acquisition risks according to phases of the indicated process, with comparison of individual risk ratings, based on the publications by authors from Central and Eastern Europe and other countries around the world. The ranking of risks and threats of mergers/acquisitions proposed in this work can be considered one of the most complete for today. Further research needs to focus on the analysis, evaluation, and modeling of merger/acquisition risks, which occupy the top of the ranking, presented by the article.

  7. 48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note: This...

  8. Status report of data acquisition

    International Nuclear Information System (INIS)

    Endo, Ichita

    1982-01-01

    The data acquisition system for the experiment with TRISTAN at KEK is discussed. For the standardization of the data bus, CAMAC-based system with possible improvement and FASTBUS being proposed by the US NIM committee were considered. The CAMAC has the disadvantages in the card size and the connectors. The card size is too small to house an intelligent circuit on a single board. The connectors cause most of troubles during the experiment. The FASTBUS is quite attractive from the viewpoint of the flexibility in bus speed and device size, although there is no commercially available FASTBUS device yet. It is not likely that other new data bus than CAMAC and FASTBUS is adopted by KEK for TRISTAN experiment. With respect to a standard microprocessor, an MC68000 (16 bit) has been picked up. The following items are being prepared by KEK to give support to users: i) the cross software of the MC68000 on the M200 H or PDP11, ii) the interface board for a personal computer equipped with a MC68000 chip to the FASTBUS and iii) a single board microprocessor module to be inserted in a FASTBUS crate. As for a host computer, a 32 bit minicomputer will be selected in 1982. (Ito, K.)

  9. Simulations of seismic acquisition footprint

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J.; Margrave, G.; Lawton, D. [Calgary Univ., AB (Canada)

    2008-07-01

    Numerical simulations were performed to investigate the causes of commonly observed artefacts in seismic field data. These seismic acquisition footprints typically consist of modulations in recorded amplitudes that are spatially correlated to the surface locations of sources and receivers used in a survey. Two broad classes of footprint were considered, notably amplitude variations related to the edges of the survey and the amplitude variations in the interior of the survey. The variations in amplitude obscure the true reflection response of the subsurface. The MATLAB numerical modelling code was used to produce the synthetic seismic data and create a thorough dataset using a survey design incorporating dense grids of sources and receivers. The footprint consisting of periodic amplitude variations in the interior of the surveys, similar to that observed in field data and likely produced by poor sampling, was observed in the decimated dataset. This type of footprint varied in strength between images produced with different processing algorithms. The observed footprint in these simulations was most organized in the unmigrated stack and was somewhat randomized after poststack. 2 refs., 1 tab., 3 figs.

  10. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage

    DEFF Research Database (Denmark)

    Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta

    2015-01-01

    (CTCL), a disease that is progressive, chemoresistant and refractory to treatment. We tested the effect of ellipticine in three cell lines with different p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored...... the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage....... Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma....

  11. Acquisition Path Analysis as a Collaborative Activity

    International Nuclear Information System (INIS)

    Nakao, A.; Grundule, R.; Gushchyn, K.; El Gebaly, A.; Higgy, R.; Tsvetkov, I.; Mandl, W.

    2015-01-01

    In the International Atomic Energy Agency, acquisition path analysis (APA) is indispensable to safeguards implementation. It is an integral part of both State evaluation process and the development of State level safeguards approaches, all performed through ongoing collaborative analysis of all available safeguards relevant information by State evaluation groups (SEG) with participation of other contributors, as required. To perform comprehensive State evaluation, to develop and revise State-level safeguards approaches, and to prepare annual implementation plans, the SEG in its collaborative analysis follows accepted safeguards methodology and guidance. In particular, the guide ''Performing Acquisition Path Analysis for the Development of a State-level Safeguards Approach for a State with a CSA'' is used. This guide identifies four major steps of the APA process: 1. Consolidating information about the State's past, present and planned nuclear fuel cycle-related capabilities and infrastructure; 2. Identifying and visually presenting technically plausible acquisition paths for the State; 3. Assessing acquisition path steps (State's technical capabilities and possible actions) along the identified acquisition paths; and 4. Assessing the time needed to accomplish each identified technically plausible acquisition path for the State. The paper reports on SEG members' and other contributors' experience with APA when following the above steps, including the identification of plausible acquisition pathways, estimation of time frames for all identified steps and determination of the time needed to accomplish each acquisition path. The difficulties that the SEG encountered during the process of performing the APA are also addressed. Feedback in the form of practical suggestions for improving the clarity of the acquisition path step assessment forms and a proposal for software support are also included. (author)

  12. Live forensic acquisition as alternative to traditional forensic processes

    CSIR Research Space (South Africa)

    Lessing, M

    2008-09-01

    Full Text Available The development of live forensic acquisition in general presents a remedy for some of the problems introduced by traditional forensic acquisition. However, this live forensic acquisition introduces a variety of additional problems, unique...

  13. 48 CFR 32.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... procedures financing. 32.003 Section 32.003 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 32.003 Simplified acquisition procedures financing. Unless agency regulations otherwise permit, contract financing shall not be provided for...

  14. Acquisition patterns of financial products : A longitudinal investigation

    NARCIS (Netherlands)

    Paas, Leonard J.; Bijmolt, Tammo H. A.; Vermunt, Jeroen K.

    Acquisition pattern analysis investigates orders in which households acquire products. Extant empirical studies employ cross-sectional data, providing limited insight into acquisition orders and no insight into timing of product acquisitions. We use an extensive longitudinal database for studying

  15. Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

    Directory of Open Access Journals (Sweden)

    Louis Chesler

    2008-11-01

    Full Text Available Chemoresistance in neuroblastoma is a significant issue complicating treatment of this common pediatric solid tumor. MYCN-amplified neuroblastomas are infrequently mutated at p53 and are chemosensitive at diagnosis but acquire p53 mutations and chemoresistance with relapse. Paradoxically, Myc-driven transformation is thought to require apoptotic blockade. We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy. Tumors formed with high penetrance and low latency in p53-haploinsufficient TH-MYCN mice. Cyclophosphamide (CPM induced a complete remission in p53 wild type TH-MYCN tumors, mirroring the sensitivity of childhood neuroblastoma to this agent. Treated tumors showed a prominent proliferation block, induction of p53 protein, and massive apoptosis proceeding through induction of the Bcl-2 homology domain-3-only proteins PUMA and Bim, leading to the activation of Bax and cleavage of caspase-3 and -9. Apoptosis induced by CPM was reduced in p53-haploinsufficient tumors. Treatment of MYCN-expressing human neuroblastoma cell lines with CPM induced apoptosis that was suppressible by siRNA to p53. Taken together, the results indicate that the p53 pathway plays a significant role in opposing MYCN-driven oncogenesis in a mouse model of neuroblastoma and that basal inactivation of the pathway is achieved in progressing tumors. This, in part, explains the striking sensitivity of such tumors to chemotoxic agents that induce p53-dependent apoptosis and is consistent with clinical observations that therapy-associated mutations in p53 are a likely contributor to the biology of tumors at relapse and secondarily mediate resistance to therapy.

  16. Developing Program Management Leadership for Acquisition Reform

    Science.gov (United States)

    2011-04-30

    mêçÅÉÉÇáåÖë= çÑ=íÜÉ= bfdeqe=^kkr^i=^`nrfpfqflk== obpb^o`e=pvjmlpfrj== qeropa^v=pbppflkp== slirjb ff Developing Program Management Leadership for...4. TITLE AND SUBTITLE Developing Program Management Leadership for Acquisition Reform 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...Developing Program  Management   Leadership   for Acquisition Reform    The 8th Annual Acquisition Research Symposium Panel #20: Investing in People

  17. An integrated acquisition, display, and analysis system

    International Nuclear Information System (INIS)

    Ahmad, T.; Huckins, R.J.

    1987-01-01

    The design goal of the ND9900/Genuie was to integrate a high performance data acquisition and display subsystem with a state-of-the-art 32-bit supermicrocomputer. This was achieved by integrating a Digital Equipment Corporation MicroVAX II CPU board with acquisition and display controllers via the Q-bus. The result is a tightly coupled processing and analysis system for Pulse Height Analysis and other applications. The system architecture supports distributed processing, so that acquisition and display functions are semi-autonomous, making the VAX concurrently available for applications programs

  18. TFTR diagnostic control and data acquisition system

    International Nuclear Information System (INIS)

    Sauthoff, N.R.; Daniels, R.E.; PPL Computer Division

    1985-01-01

    General computerized control and data-handling support for TFTR diagnostics is presented within the context of the Central Instrumentation, Control and Data Acquisition (CICADA) System. Procedures, hardware, the interactive man--machine interface, event-driven task scheduling, system-wide arming and data acquisition, and a hierarchical data base of raw data and results are described. Similarities in data structures involved in control, monitoring, and data acquisition afford a simplification of the system functions, based on ''groups'' of devices. Emphases and optimizations appropriate for fusion diagnostic system designs are provided. An off-line data reduction computer system is under development

  19. Acquisition of speech rhythm in first language.

    Science.gov (United States)

    Polyanskaya, Leona; Ordin, Mikhail

    2015-09-01

    Analysis of English rhythm in speech produced by children and adults revealed that speech rhythm becomes increasingly more stress-timed as language acquisition progresses. Children reach the adult-like target by 11 to 12 years. The employed speech elicitation paradigm ensured that the sentences produced by adults and children at different ages were comparable in terms of lexical content, segmental composition, and phonotactic complexity. Detected differences between child and adult rhythm and between rhythm in child speech at various ages cannot be attributed to acquisition of phonotactic language features or vocabulary, and indicate the development of language-specific phonetic timing in the course of acquisition.

  20. Combined Acquisition/Processing For Data Reduction

    Science.gov (United States)

    Kruger, Robert A.

    1982-01-01

    Digital image processing systems necessarily consist of three components: acquisition, storage/retrieval and processing. The acquisition component requires the greatest data handling rates. By coupling together the acquisition witn some online hardwired processing, data rates and capacities for short term storage can be reduced. Furthermore, long term storage requirements can be reduced further by appropriate processing and editing of image data contained in short term memory. The net result could be reduced performance requirements for mass storage, processing and communication systems. Reduced amounts of data also snouid speed later data analysis and diagnostic decision making.

  1. Multi-user data acquisition environment

    International Nuclear Information System (INIS)

    Storch, N.A.

    1983-01-01

    The typical data acquisition environment involves data collection and monitoring by a single user. However, in order to support experiments on the Mars facility at Lawrence Livermore National Laboratory, we have had to create a multi-user data acquisition environment where any user can control the data acquisition and several users can monitor and analyze data being collected in real time. This paper describes how we accomplished this on an HP A600 computer. It focuses on the overall system description and user communication with the tasks within the system. Our current implementation is one phase of a long-term software development project

  2. A data acquisition architecture for the SSC

    International Nuclear Information System (INIS)

    Partridge, R.

    1990-01-01

    An SSC data acquisition architecture applicable to high-p T detectors is described. The architecture is based upon a small set of design principles that were chosen to simplify communication between data acquisition elements while providing the required level of flexibility and performance. The architecture features an integrated system for data collection, event building, and communication with a large processing farm. The interface to the front end electronics system is also discussed. A set of design parameters is given for a data acquisition system that should meet the needs of high-p T detectors at the SSC

  3. Manganese acquisition by Lactobacillus plantarum

    Energy Technology Data Exchange (ETDEWEB)

    Archibald, F.S.; Duong, M.N.

    1984-04-01

    Lactobacillus plantarum has an unusually high Mn(II) requirement for growth and accumulated over 30 mM intracellular Mn(II). The acquisition of Mn(II) by L. plantarum occurred via a specific active transport system powered by the transmembrane proton gradient. The Mn(II) uptake system has a K/sub m/ of 0.2 ..mu..M and a V/sub max/ of 24 nmol mg/sup -1/ of protein min/sup -1/. Above a medium Mn(II) concentration of 200 ..mu..M, the intracellular Mn(II) level was independent of the medium Mn(II) and unresponsive to oxygen stresses but was reduced by phosphate limitation. At a pH of 5.5, citrate, isocitrate, and cis-aconitate effectively promoted MN(II) uptake, although measurable levels of 1,5-(/sup 14/C)citrate were not accumulated. When cells were presented with equimolar Mn(II) and Cd(II), Cd(II) was preferentially taken up by the Mn(II) transport system. Both Mn(II) and Cd(II) uptake were greatly increased by Mn(II) starvation. Mn(II) uptake by Mn(II)-starved cells was subject to a negative feedback regulatory mechanism functioning less than 1 min after exposure of the cells to Mn(II) and independent of protein synthesis. When presented with a relatively large amount of exogenous Mn(II), Mn(II)-starved cells exhibited a measurable efflux of their internal Mn(II), but the rate was only a small fraction of the maximal Mn(II) uptake rate.

  4. Developing Air Force Acquisition Leaders for the 21st Century

    National Research Council Canada - National Science Library

    Latin, Anita

    2003-01-01

    ... direction, skills, training and education, career management guidance, and leadership and command opportunities to nurture, develop, and retain acquisition officers to become the best strategic acquisition leaders...

  5. IT-based Value Creation in Serial Acquisitions

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Yetton, Philip

    2013-01-01

    serial acquirers realize IT-based value, we integrate and model the findings on individual acquisitions from the extant literature, and extend that model to explain the effects of sequential acquisitions in a growth-by-acquisition strategy. This extended model, drawing on the Resource-Based Theory......The extant research on post-acquisition IT integration analyzes how acquirers realize IT-based value in individual acquisitions. However, serial acquirers make 60% of acquisitions. These acquisitions are not isolated events, but are components in growth-by-acquisition programs. To explain how...

  6. Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-13-1-0162 TITLE: Using a Novel Transgenic Mouse Model to Study c -Myc Oncogenic Pathway in Castration Resistance and...DATES COVERED 15Sept2013 - 14Sept2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Using a Novel Transgenic Mouse Model to Study c -Myc Oncogenic...ABSTRACT We previously made a PB-Cre4/Ai-Myc model for Cre-induced and androgen-independent expression of c -Myc and Luc2 in prostate. This is designed

  7. Advanced Mars Water Acquisition System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Mars Water Acquisition System (AMWAS) recovers and purifies water from Mars soils for oxygen and fuel production, life support, food production, and...

  8. Liforac - A Model For Live Forensic Acquisition

    CSIR Research Space (South Africa)

    Grobler, MM

    2009-10-01

    Full Text Available ways in which such an acquisition should take place to ensure forensic soundness. The study presents information on a relatively new field of expertise and considers the Digital Forensic discipline, forensic tools, practical problems experienced during...

  9. Summary of DOD Acquisition Program Audit Coverage

    National Research Council Canada - National Science Library

    2001-01-01

    This report will provide the DoD audit community with information to support their planning efforts and provide management with information on the extent of audit coverage of DoD acquisition programs...

  10. Unique portable signal acquisition/processing station

    International Nuclear Information System (INIS)

    Garron, R.D.; Azevedo, S.G.

    1983-01-01

    At Lawrence Livermore National Laboratory, there are experimental applications requiring digital signal acquisition as well as data reduction and analysis. A prototype Signal Acquisition/Processing Station (SAPS) has been constructed and is currently undergoing tests. The system employs an LSI-11/23 computer with Data Translation analog-to-digital hardware. SAPS is housed in a roll-around cart which has been designed to withstand most subtle EMI/RFI environments. A user-friendly menu allows a user to access powerful data acquisition packages with a minimum of training. The software architecture of SAPS involves two operating systems, each being transparent to the user. Since this is a general purpose workstation with several units being utilized, an emphasis on low cost, reliability, and maintenance was stressed during conception and design. The system is targeted for mid-range frequency data acquisition; between a data logger and a transient digitizer

  11. MITS Data Acquisition Subsystem Acceptance Test procedure

    International Nuclear Information System (INIS)

    Allison, R.

    1980-01-01

    This is an acceptance procedure for the Data Acquisition Subsystem of the Machine Interface Test System (MITS). Prerequisites, requirements, and detailed step-by-step instruction are presented for inspecting and performance testing the subsystem

  12. Mergers and acquisitions: a most strategic decision.

    Science.gov (United States)

    Laine, Mike; Tyler, David

    2007-11-01

    Five steps are basic to successfully concluding (or deciding not to conclude) a merger or acquisition: Identify targets. Begin with the end in mind. Choose a transaction team. Perform due diligence. Commit to the deal--or to no deal.

  13. A marine meteorological data acquisition system

    Digital Repository Service at National Institute of Oceanography (India)

    Desai, R.G.P.; Desa, E.; Vithayathil, G.

    A marine meteorological data acquisition system has been developed for long term unattended measurements at remote coastal sites, ocean surface platforms and for use on board research vessels. The system has an open and modular configuration...

  14. Innovative UK Approaches to Acquisition Management

    Science.gov (United States)

    2009-05-01

    Financial and Operational Imperatives Size of UK armed forces UK Industry ? Political influence PFI / PPP Increased Scrutiny - NAO “ Commercialisation “ of the...acquisition KNOWLEDGE (EXPERIENCE – Lessons learned) KNOWLEDGE (Training) KNOWLEDGE ( Education ) OPTIMAL OPERATIONAL PERFORMANCE Operational Capability UK

  15. 75 FR 10567 - Commerce Acquisition Regulation (CAR)

    Science.gov (United States)

    2010-03-08

    ... regulations, Federal acquisition regulations, Government procurement, Government contracts, Procurement, Reporting and recordkeeping requirements. 48 CFR Part 1302 Definitions, Government procurement, Terms. 48 CFR Part 1303 Antitrust, Conflict of interests, Ethical conduct, Government procurement, Reporting and...

  16. AcquisitionFootprintAttenuationDrivenbySeismicAttributes

    Directory of Open Access Journals (Sweden)

    Cuellar-Urbano Mayra

    2014-04-01

    Full Text Available Acquisition footprint, one of the major problems that PEMEX faces in seismic imaging, is noise highly correlated to the geometric array of sources and receivers used for onshore and offshore seismic acquisitions. It prevails in spite of measures taken during acquisition and data processing. This pattern, throughout the image, is easily confused with geological features and misguides seismic attribute computation. In this work, we use seismic data from PEMEX Exploración y Producción to show the conditioning process for removing random and coherent noise using linear filters. Geometric attributes used in a workflow were computed for obtaining an acquisition footprint noise model and adaptively subtract it from the seismic data.

  17. Triggering and data acquisition general considerations

    International Nuclear Information System (INIS)

    Butler, Joel N.

    2003-01-01

    We provide a general introduction to trigger and data acquisition systems in High Energy Physics. We emphasize the new possibilities and new approaches that have been made possible by developments in computer technology and networking

  18. Technological Integration of Acquisitions in Digital Industries

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Toppenberg, Gustav

    2015-01-01

    providers to extend the platform core and to derive network effects by consolidating platform user groups, and (b) complement providers to create monopoly positions for the complements and for innovation complementarity. To enable these acquisition benefits, acquirers face technological integration...... challenges in process and product integration. Through a case study of Network Solutions Corp. (NSC), a Fortune 500 company that has acquired more than 175 business units, we develop four propositions explaining how the benefits of platform core and complement acquisitions are differently contingent......Acquisitions have become essential tools to retain the technological edge in digital industries. This paper analyses the technological integration challenges in such acquisitions. Acquirers in digital industries are typically platform leaders in platform markets. They acquire (a) other platform...

  19. Data acquisition in the EUDET project

    Indian Academy of Sciences (India)

    with emphasis on issues related to data acquisition for future test beam experiments. Keywords. ... working in the field of high energy physics. In addition .... processor for gas detectors, Open Access article, Published in: IEEE Trans. Nucl. Sci.

  20. Generative Research on Second Language Acquisition.

    Science.gov (United States)

    Eubank, Lynn

    1995-01-01

    Reviews recent trends in generative research on second language acquisition, focusing on the role of universal grammar, parameter resetting, and anaphoric binding. An annotated bibliography discusses five important works in the field. (61 references) (MDM)

  1. French bank mergers and acquisitions performance

    Directory of Open Access Journals (Sweden)

    Houda Ben Said

    2017-11-01

    Full Text Available In this paper, we empirically investigate the impact of mergers and acquisitions on French bank performance. Performance is measured by potential gains in efficiency and value creation. We first analyzed efficiency using the data envelopment analysis (DEA under input oriented with variable returns to scale to obtain the efficiency scores. Second, we analyzed the impact on French bank value creation following mergers-acquisitions operations of a set of control variables (model 1 and explicative variables measuring strategic similarities between bidders and targets (model 2. The sample studied is composed of French bank mergers-acquisitions happening between 1996 and 2006 and implying one of the 14 greatest French banking groups. Empirical result showed that mergers and acquisitions have been traduced by an improvement in the overall efficiency by 17.82% and a shareholder value reduction by 5.14%

  2. Acquisition Reform: "This, Too, Shall Pass..?"

    National Research Council Canada - National Science Library

    Munechika, Curtis

    1997-01-01

    .... Will this effort too, come, and go? This paper attempts to answer this question by comparing the past efforts in implementing acquisition reform to today today's efforts using the backdrop of current organizational change theories...

  3. The CMD-3 Data Acquisition System

    CERN Document Server

    Kozyrev, A N; Epifanov, D A; Epshteyn, L B; Logashenko, I B; Mikhailov, K Yu; Popov, A S; Ruban, A A; Selivanov, A N; Talyshev, A A; Titov, V M; Yudin, Y V

    2017-01-01

    The specialized data acquisition system designed for CMD-3 detector which is installed at the electron-positron collider VEPP-2000 to the Budker Institute of Nuclear Physics, Novosibirsk, Russia. The structure of electronic hardware and firmware is described.

  4. Using Architectures for Research, Development, and Acquisition

    National Research Council Canada - National Science Library

    Dickerson, C

    2004-01-01

    The goal of this book is to show how architectures can be used to enable a capabilities-based approach to the research, development, and acquisition of DoD families of systems that must interoperate...

  5. Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response.

    Science.gov (United States)

    Long, J; Fang, W Y; Chang, L; Gao, W H; Shen, Y; Jia, M Y; Zhang, Y X; Wang, Y; Dou, H B; Zhang, W J; Zhu, J; Liang, A B; Li, J M; Hu, Jiong

    2017-12-01

    Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9 + leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.

  6. A Lossless Network for Data Acquisition

    OpenAIRE

    Jereczek, Grzegorz Edmund; Lehmann Miotto, Giovanna

    2016-01-01

    The bursty many-to-one communication pattern, typical for data acquisition systems, is particularly demanding for commodity TCP/IP and Ethernet technologies. We expand the study of lossless switching in software running on commercial-off-the-shelf servers, using the ATLAS experiment as a case study. In this paper we extend the popular software switch, Open vSwitch, with a dedicated, throughput-oriented buffering mechanism for data acquisition. We compare the performance under heavy congestion...

  7. Analysis of the SIAM Infrared Acquisition System

    Energy Technology Data Exchange (ETDEWEB)

    Varnado, S.G.

    1974-02-01

    This report describes and presents the results of an analysis of the performance of the infrared acquisition system for a Self-Initiated Antiaircraft Missile (SIAM). A description of the optical system is included, and models of target radiant intensity, atmospheric transmission, and background radiance are given. Acquisition probabilities are expressed in terms of the system signal-to-noise ratio. System performance against aircraft and helicopter targets is analyzed, and background discrimination techniques are discussed. 17 refs., 22 figs., 6 tabs.

  8. Incidental Lexicon Acquisition through Playful Interaction

    OpenAIRE

    Lukas Wilhelm Ansteeg

    2015-01-01

    This paper presents an educational game which aids learners with foreign lexicon acquisition while entertaining them at the same time. An overview over existing language learning tools is given, and a general platform for educational games for second language acquisition (SLA) is described. It introduces a specific prototype video game which teaches Italian vocabulary to the user. The application puts learning at the core of its game mechanics and combines it with a narrative and role-playing...

  9. Acquisition Modernization: Transitioning Technology Into Warfighter Capability

    Science.gov (United States)

    2011-08-01

    to test and evaluate the technology and integrate the new capability into operational weapon systems (Figure 4). This funding model creates stove...misalignment between missions, TRLs, and the RDT&E funding model is a major 11 contributor to the valley of death. Technologies become obsolete on... funding model of the acquisition system. Create an individual budget account to fund the development of promising technologies. The Acquisition

  10. Defense Acquisition Reform, 19602009: An Elusive Goal

    Science.gov (United States)

    2011-10-31

    the seven largest economies of the world (United States, China, Japan, Germany, France, United Kingdom, and Italy ).11 Major weapon systems...the Federal Acquisition Regulation.96 95 Ibid., pp. 20, 21. 96 Joseph Ferrara , “DoD’s 5000 Documents: Evolution and Change in Defense Acquisition...Wayne Smith. How Much Is Enough: Shaping the Defense Program, 1961–1969. New York: Harper & Row, 1971. Ferrara , Joseph. “DoD’s 5000 Documents

  11. DABASCO Experiment Data Acquisition and Control System

    International Nuclear Information System (INIS)

    Alberdi Primicia, J.; Artigao Arteaga, A.; Barcala Rieveira, J. M.; Oller Gonzalez, J. C.

    2000-01-01

    DABASCO experiment wants to study the thermohydraulic phenomena produced into the containment area for a severe accident in a nuclear power facility. This document describes the characteristics of the data acquisition and control system used in the experiment. The main elements of the system were a data acquisition board, PCI-MIO-16E-4, and an application written with LaB View. (Author) 5 refs

  12. Introduction : language acquisition and sociolinguistic variation

    OpenAIRE

    Chevrot, Jean-Pierre; Foulkes, Paul

    2013-01-01

    International audience; The special issue appears in a new scientific landscape of innovative attempts to link sociolinguistics and cognitive psycholinguistics. Studies on acquisition of variation have been conducted since the late 1960s, but the changing scientific landscape gives them a new impetus. On the one hand, our work draws on and contributes to sociolinguistics. As a result, it focuses on the acquisition of sociolinguistic patterns conceived of as properties shared by communities of...

  13. Technological Similarity, Post-acquisition R&D Reorganization, and Innovation Performance in Horizontal Acquisition

    DEFF Research Database (Denmark)

    Colombo, Massimo G.; Rabbiosi, Larissa

    2014-01-01

    This paper aims to disentangle the mechanisms through which technological similarity between acquiring and acquired firms influences innovation in horizontal acquisitions. We develop a theoretical model that links technological similarity to: (i) two key aspects of post-acquisition reorganization...... of acquired R&D operations – the rationalization of the R&D operations and the replacement of the R&D top manager, and (ii) two intermediate effects that are closely associated with the post-acquisition innovation performance of the combined firm – improvements in R&D productivity and disruptions in R......&D personnel. We rely on PLS techniques to test our theoretical model using detailed information on 31 horizontal acquisitions in high- and medium-tech industries. Our results indicate that in horizontal acquisitions, technological similarity negatively affects post-acquisition innovation performance...

  14. Acoustic window planning for ultrasound acquisition.

    Science.gov (United States)

    Göbl, Rüdiger; Virga, Salvatore; Rackerseder, Julia; Frisch, Benjamin; Navab, Nassir; Hennersperger, Christoph

    2017-06-01

    Autonomous robotic ultrasound has recently gained considerable interest, especially for collaborative applications. Existing methods for acquisition trajectory planning are solely based on geometrical considerations, such as the pose of the transducer with respect to the patient surface. This work aims at establishing acoustic window planning to enable autonomous ultrasound acquisitions of anatomies with restricted acoustic windows, such as the liver or the heart. We propose a fully automatic approach for the planning of acquisition trajectories, which only requires information about the target region as well as existing tomographic imaging data, such as X-ray computed tomography. The framework integrates both geometrical and physics-based constraints to estimate the best ultrasound acquisition trajectories with respect to the available acoustic windows. We evaluate the developed method using virtual planning scenarios based on real patient data as well as for real robotic ultrasound acquisitions on a tissue-mimicking phantom. The proposed method yields superior image quality in comparison with a naive planning approach, while maintaining the necessary coverage of the target. We demonstrate that by taking image formation properties into account acquisition planning methods can outperform naive plannings. Furthermore, we show the need for such planning techniques, since naive approaches are not sufficient as they do not take the expected image quality into account.

  15. Acquisition: Implementation of the DoD Management Control Program for Navy Acquisition Category II and III Programs

    National Research Council Canada - National Science Library

    2004-01-01

    ... deviations in cost, schedule, and performance requirements in acquisition program baselines for Acquisition Category II and III programs and in identifying whether program managers are reporting...

  16. Acquisitions Everywhere: Modeling an Acquisitions Data Standard to Connect a Distributed Environment

    OpenAIRE

    Hanson, Eric M.; Lightcap, Paul W.; Miguez, Matthew R.

    2016-01-01

    Acquisitions functions remain operationally crucial in providing access to paid information resources, but data formats and workflows utilized within library acquisitions remain primarily within the traditional integrated library system (ILS). As libraries have evolved to use distributed systems to manage information resources, so too must acquisitions functions adapt to an environment that may include the ILS, e‐resource management systems (ERMS), institutional repositories (IR), and other d...

  17. Design of the M&S acquisition support effort of the SANDF GBADS acquisition programme

    CSIR Research Space (South Africa)

    Nel, JJ

    2007-06-01

    Full Text Available (AmADS) GBADS Phase 2 (MobADS) GBADS Phase 3 (LmADS) GBADS Phase 4 (C2 Optimisation) GBADS Phase 5 (MecADS) Figure 1: GBADS Phased Acquisition. The acquisition programme comprises five phases each addressing the acquisition of a specific... element of the GBADS. Phase 1 addresses an Air-mobile Air Defence System (AmADS) utilising man-portable missiles that can also be employed as a component of a Mobile Air Defence System (MobADS). Phase 2 involves the acquisition of the remainder...

  18. The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view.

    Science.gov (United States)

    El Sayed, Salah Mohamed; Baghdadi, Hussam; Zolaly, Mohammed; Almaramhy, Hamdi H; Ayat, Mongi; Donki, Jagadish G

    2017-03-01

    3-Bromopyruvate (3BP) is a promising effective anticancer drug against many different tumors in children and adults. 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect. There is no report about 3BP metabolism to guide researchers and oncologists to improve clinical practice and prevent drug resistance. In this article, we provide evidences that 3BP is metabolized through glutathione (GSH) conjugation as a novel report where 3BP was confirmed to be attached to GSH followed by permanent loss of pharmacological effects in a picture similar to cisplatin. Both cisplatin and 3BP are alkylating agents. Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i.e. GSH consumption for conjugation with 3BP. Cancer cells having high endogenous GSH exhibit resistance to 3BP while 3BP sensitive cells acquire resistance upon adding exogenous GSH. Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH. That may decrease 3BP-induced anticancer effects and the functions of those proteins. We proved here that 3BP metabolism is different from metabolism of hydroxypyruvate that results from metabolism of D-serine using D-amino acid oxidase. Clinically, 3BP administration should be monitored during albumin infusion and protein therapy where GSH should be added to emergency medications. GSH exerts many physiological effects and is safe for human administration both orally and intravenously. Based on that, reported GSH-induced inhibition of 3BP effects makes 3BP effects reversible, easily monitored and easily controlled. This confers a superiority of 3BP over many anticancer agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents.

    Science.gov (United States)

    Xue, Kai; Gu, Juan J; Zhang, Qunling; Mavis, Cory; Hernandez-Ilizaliturri, Francisco J; Czuczman, Myron S; Guo, Ye

    2016-02-01

    Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were

  20. Acquisition and tracking for underwater optical communications

    Science.gov (United States)

    Williams, Andrew J.; Laycock, Leslie L.; Griffith, Michael S.; McCarthy, Andrew G.; Rowe, Duncan P.

    2017-10-01

    There is a growing requirement to transfer large volumes of data between underwater platforms. As seawater is transmissive in the visible band, underwater optical communications is an active area of interest since it offers the potential for power efficient, covert and high bandwidth datalinks at short to medium ranges. Short range systems have been successfully demonstrated using sources with low directionality. To realise higher data rates and/or longer ranges, the use of more efficient directional beams is required; by necessity, these must be sufficiently aligned to achieve the required link margin. For mobile platforms, the acquisition and tracking of each node is therefore critical in order to establish and maintain an optical datalink. This paper describes work undertaken to demonstrate acquisition and tracking in a 3D underwater environment. A range of optical sources, beam steering technologies, and tracking sensors have been assessed for suitability. A novel scanning strategy exploiting variable beam divergence was developed to provide robust acquisition whilst minimising acquisition time. A prototype system was assembled and demonstrated in a large water tank. This utilised custom quadrant detectors based on Silicon PhotoMultiplier (SiPM) arrays for fine tracking, and a Wide Field of View (WFoV) sCMOS camera for link acquisition. Fluidic lenses provided dynamic control of beam divergence, and AC modulation/filtering enabled background rejection. The system successfully demonstrated robust optical acquisition and tracking between two nodes with only nanowatt received optical powers. The acquisition time was shown to be dependent on the initial conditions and the transmitted optical power.

  1. Development of data acquisition system for CSNS 3He detector

    International Nuclear Information System (INIS)

    Zhao Dongxu; Zhang Hongyu

    2012-01-01

    This paper introduces the research and development of data acquisition system of CSNS 3 He detector prototype. This system provides high performance data acquisition capability of CSNS 3 He detector, as well as several performance tests of electronics prototype. This data acquisition system establishes foundation for the later data acquisition development. (authors)

  2. A Research on Second Language Acquisition and College English Teaching

    Science.gov (United States)

    Li, Changyu

    2009-01-01

    It was in the 1970s that American linguist S.D. Krashen created the theory of "language acquisition". The theories on second language acquisition were proposed based on the study on the second language acquisition process and its rules. Here, the second language acquisition process refers to the process in which a learner with the…

  3. 48 CFR 3032.003 - Simplified acquisition procedures financing.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Simplified acquisition procedures financing. 3032.003 Section 3032.003 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND... FINANCING Scope of Part 3032.003 Simplified acquisition procedures financing. Contract financing may be...

  4. 10 CFR 626.4 - General acquisition strategy.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false General acquisition strategy. 626.4 Section 626.4 Energy DEPARTMENT OF ENERGY (CONTINUED) SALES REGULATION PROCEDURES FOR ACQUISITION OF PETROLEUM FOR THE STRATEGIC PETROLEUM RESERVE § 626.4 General acquisition strategy. (a) Criteria for commencing acquisition. To reduce...

  5. 32 CFR 644.102 - Examples of involuntary acquisitions.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Examples of involuntary acquisitions. 644.102... PROPERTY REAL ESTATE HANDBOOK Acquisition Involuntary Acquisition by the United States § 644.102 Examples... property, as prescribed by Pub. L. 91-646. Examples of involuntary acquisition are: (a) Damage to real...

  6. 48 CFR 1.102-3 - Acquisition team.

    Science.gov (United States)

    2010-10-01

    ... service. By identifying the team members in this manner, teamwork, unity of purpose, and open... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acquisition team. 1.102-3... ACQUISITION REGULATIONS SYSTEM Purpose, Authority, Issuance 1.102-3 Acquisition team. The purpose of defining...

  7. Anti-apoptotic ARC protein confers chemoresistance by controlling leukemia-microenvironment interactions through a NFκB/IL1β signaling network

    KAUST Repository

    Carter, Bing Z.; Mak, Po Yee; Chen, Ye; Mak, Duncan H.; Mu, Hong; Jacamo, Rodrigo; Ruvolo, Vivian; Arold, Stefan T.; Ladbury, John E.; Burks, Jared K.; Kornblau, Steven; Andreeff, Michael

    2016-01-01

    To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB. Expression of these chemokines in MSCs increased by AML cells in an ARC/IL1β-dependent manner; likewise, IL1β expression was elevated when leukemia cells were co-cultured with MSCs. Further, cells from AML patients expressed the receptors for and migrated toward CCL2, CCL4, and CXCL12. Inhibition of IL1β suppressed AML cell migration and sensitized the cells co-cultured with MSCs to chemotherapy. Our results suggest the existence of a complex ARC-regulated circuit that maintains intimate connection of AML with the tumor microenvironment through NFκB/IL1β-regulated chemokine receptor/ligand axes and reciprocal crosstalk resulting in cytoprotection. The data implicate ARC as a promising drug target to potentially sensitize AML cells to chemotherapy.

  8. Anti-apoptotic ARC protein confers chemoresistance by controlling leukemia-microenvironment interactions through a NFκB/IL1β signaling network

    KAUST Repository

    Carter, Bing Z.

    2016-04-11

    To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB. Expression of these chemokines in MSCs increased by AML cells in an ARC/IL1β-dependent manner; likewise, IL1β expression was elevated when leukemia cells were co-cultured with MSCs. Further, cells from AML patients expressed the receptors for and migrated toward CCL2, CCL4, and CXCL12. Inhibition of IL1β suppressed AML cell migration and sensitized the cells co-cultured with MSCs to chemotherapy. Our results suggest the existence of a complex ARC-regulated circuit that maintains intimate connection of AML with the tumor microenvironment through NFκB/IL1β-regulated chemokine receptor/ligand axes and reciprocal crosstalk resulting in cytoprotection. The data implicate ARC as a promising drug target to potentially sensitize AML cells to chemotherapy.

  9. Knowledge-sharing Behavior and Post-acquisition Integration Failure

    DEFF Research Database (Denmark)

    Gammelgaard, Jens; Husted, Kenneth; Michailova, Snejina

    2004-01-01

    AbstractNot achieving the anticipated synergy effects in the post-acquisition integration context is a serious causefor the high acquisition failure rate. While existing studies on failures of acquisitions exist fromeconomics, finance, strategy, organization theory, and human resources management......, this paper appliesinsights from the knowledge-sharing literature. The paper establishes a conceptual link between obstaclesin the post-acquisition integration processes and individual knowledge-sharing behavior as related toknowledge transmitters and knowledge receivers. We argue that such an angle offers...... important insights toexplaining the high failure rate in acquisitions.Descriptors: post-acquisition integration, acquisition failure, individual knowledge-sharing behavior...

  10. Analysis of International Mergers and Acquisitions in the Pharmaceutical Industry

    Directory of Open Access Journals (Sweden)

    Božo Matić

    2011-07-01

    Full Text Available There are numerous researches which analyze mergers and acquisitions, but most of them do not focus on a certain industry, but their sample considers companies from different industries. This paper focuses on mergers and acquisitions in the pharmaceutical industry. It is assumed that pharmaceutical companies with no experience in mergers and acquisitions achieve better results in relatively small and domestic mergers and acquisitions while pharmaceutical companies with greater experience in mergers and acquisitions are successful even in bigger and international mergers and acquisitions. Bigger mergers and acquisitions and international mergers and acquisitions are more risky for the companies so lack of experience in mergers and acquisitions additionally increases risks during the process of mergers and acquisitions. On average, such increase of the risk results in lower returns for stock owners of pharmaceutical companies.

  11. 75 FR 14057 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-40; Introduction

    Science.gov (United States)

    2010-03-23

    ... the Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council (Councils) in..., consider all the information in FAPIIS and PPIRS when making a responsibility determination, and notify the... appropriate for the official's consideration; and Enter a non-responsibility determination into FAPIIS. The...

  12. 75 FR 52650 - Defense Federal Acquisition Regulation Supplement; Acquisition of Commercial Items (2008-D011)

    Science.gov (United States)

    2010-08-27

    ...: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Interim rule; delay in... rule that amended the Defense Federal Acquisition Regulation Supplement (DFARS) to implement sections... comments on the interim rule were located, which had not been addressed in finalization of the interim rule...

  13. 75 FR 53127 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-45; Introduction

    Science.gov (United States)

    2010-08-30

    ... summarizes the Federal Acquisition Regulation (FAR) rules agreed to by the Civilian Agency Acquisition... Chambers. Cost or Pricing Data. III American Recovery 2009-008 Davis. and Reinvestment Act of 2009 (the Recovery Act)-- Buy American Requirements for Construction Materials. SUPPLEMENTARY INFORMATION: Summaries...

  14. Dual isotope, single acquisition parathyroid imaging

    International Nuclear Information System (INIS)

    Triantafillou, M.; McDonald, H.J.

    1998-01-01

    Full text: Nuclear Medicine parathyroid imaging using Thallium-201(TI) and Technetium-99m(Tc) is an often used imaging modality for the detection of parathyroid adenomas and hyper parathyroidism. The conventional Tl/Tc subtraction technique requires 2 separate injections and acquisitions which are then normalised and subtracted from each other. This lengthy technique is uncomfortable for patients and can result in false positive scan results due to patient movement between and during the acquisition process. We propose a simplified injection and single acquisition technique, that reduces the chance of movement and thus reduces the chance of false positive scan results. The technique involves the injection of Tc followed by the Tl injection 10 minutes later. After a further 10 min wait, imaging is performed using a dual isotope acquisition, with window (W) 1 set on 140 keV 20%W 5% off peak and W2 peaked for 70 keV 20%W., acquired for 10 minutes. We have imaged 27 patients with this technique, 15 had positive parathyroid imaging. Of the 15, 11 had positive ultrasound correlation. Of the remaining 4, 2 have had positive surgical findings for adenomas, the other 2 are awaiting follow-up. Of the 12 patients with negative parathyroid imaging, 2 have been shown to be false - negative with surgery. In conclusion, the single acquisition technique suggested by us is a valid method of imaging parathyroids that reduces the chance of false positive results due to movement

  15. Data acquisition system for nuclear reactor environment

    International Nuclear Information System (INIS)

    Tiwari, Akash; Tiwari, Railesha; Tiwari, S.S.; Panday, Lokesh; Suri, Nitin; Chouksey, Abhsek; Singh, Sarvesh Kumar; Dwivedi, Tarun; Agrawal, Ashish; Pandey, Pranav Kumar; Sharma, Brijnandan; Bhatia, Chirag

    2004-01-01

    We have designed an online real time data acquisition system for nuclear reactor environment monitoring. Data acquisition system has eight channels of analog signals and one channel of pulsed input signal from detectors like GM Tube, or any other similar input. Connectivity between the data acquisition system and environmental parameters monitoring computer is made through a wireless data communication link of 151 MHz/100 mW RF power and 10 km maximum communication range for remote data telemetry. Sensors used are gamma ionizing radiation sensor made from CsI:Tl scintillator, atmospheric pressure sensor with +/-0.1 mbar precision, temperature sensor with +/-l milli degree Celsius precision, relative humidity with +/-0.1RH precision, pulse counts with +/-1 count in 0-10000 Hz count rate measurement precision and +/-1 count is accumulated count measurement precision. The entire data acquisition system and wireless telemetry system is 9 V battery powered and the device is to be fitted on a wireless controlled mobile robot for scanning the nuclear reactor zone from remote. Wireless video camera has been planned for integration into the existing system on a later date for moving the robotics environmental data acquisition system beyond human vision reach. System development cost is Rs.25 Lacs and has been developed for Department of Atomic Energy, Government of India and Indian Defense use. (author)

  16. Data acquisition upgrade in the RFX experiment

    International Nuclear Information System (INIS)

    Barana, O.; Luchetta, A.; Manduchi, G.; Taliercio, C.

    2005-01-01

    The control and data acquisition system of RFX has been completely renewed and is currently under re-commissioning. Most data acquisition is now performed by means of CompactPCI (CPCI) devices supervised by Pentium PCs running Linux. Real-time control systems, implemented using VME and PowerPCs running VxWorks, also produce data that are then acquired by the data acquisition system. The older CAMAC systems have only been retained for existing diagnostics. New diagnostic systems will employ either CompactPCI data acquisition or custom solutions, usually running under Windows, due to the fact that the drivers for the used devices are normally available for this platform. Despite the variety of hardware and software platforms involved in data acquisition, the same software package is used for all components, thus providing a uniform view of the system. Such functionality is provided by the MDSplus software. MDSplus is now available for a variety of platforms, and includes several Java components that are platform-independent

  17. Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    International Nuclear Information System (INIS)

    Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.; Patel, Vyomesh; Gutkind, J. Silvio; Yamada, Kenneth M.; Berrier, Allison L.

    2011-01-01

    Research highlights: → Proteomics of clustered integrin αβ1, α v β, α 6 β receptors in oral carcinoma. → p130Cas, Dek, Src and talin regulate oral carcinoma invasion. → p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin αβ1, α v β or α 6 β receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  18. Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    Energy Technology Data Exchange (ETDEWEB)

    Sansing, Hope A. [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States); Sarkeshik, Ali; Yates, John R. [Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA (United States); Patel, Vyomesh; Gutkind, J. Silvio [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yamada, Kenneth M. [Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Berrier, Allison L., E-mail: allison.berrier@gmail.com [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States)

    2011-03-11

    Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  19. Shared vision and autonomous motivation vs. financial incentives driving success in corporate acquisitions

    Science.gov (United States)

    Clayton, Byron C.

    2015-01-01

    Successful corporate acquisitions require its managers to achieve substantial performance improvements in order to sufficiently cover acquisition premiums, the expected return of debt and equity investors, and the additional resources needed to capture synergies and accelerate growth. Acquirers understand that achieving the performance improvements necessary to cover these costs and create value for investors will most likely require a significant effort from mergers and acquisitions (M&A) management teams. This understanding drives the common and longstanding practice of offering hefty performance incentive packages to key managers, assuming that financial incentives will induce in-role and extra-role behaviors that drive organizational change and growth. The present study debunks the assumptions of this common M&A practice, providing quantitative evidence that shared vision and autonomous motivation are far more effective drivers of managerial performance than financial incentives. PMID:25610406

  20. Shared vision and autonomous motivation vs. financial incentives driving success in corporate acquisitions.

    Science.gov (United States)

    Clayton, Byron C

    2014-01-01

    Successful corporate acquisitions require its managers to achieve substantial performance improvements in order to sufficiently cover acquisition premiums, the expected return of debt and equity investors, and the additional resources needed to capture synergies and accelerate growth. Acquirers understand that achieving the performance improvements necessary to cover these costs and create value for investors will most likely require a significant effort from mergers and acquisitions (M&A) management teams. This understanding drives the common and longstanding practice of offering hefty performance incentive packages to key managers, assuming that financial incentives will induce in-role and extra-role behaviors that drive organizational change and growth. The present study debunks the assumptions of this common M&A practice, providing quantitative evidence that shared vision and autonomous motivation are far more effective drivers of managerial performance than financial incentives.

  1. Shared Vision and Autonomous Motivation versus Financial Incentives Driving Success in Corporate Acquisitions

    Directory of Open Access Journals (Sweden)

    Byron C Clayton

    2015-01-01

    Full Text Available Successful corporate acquisitions require its managers to achieve substantial performance improvements in order to sufficiently cover acquisition premiums, the expected return of debt and equity investors, and the additional resources needed to capture synergies and accelerate growth. Acquirers understand that achieving the performance improvements necessary to cover these costs and create value for investors will most likely require a significant effort from mergers and acquisitions (M&A management teams. This understanding drives the common and longstanding practice of offering hefty performance incentive packages to key managers, assuming that financial incentives will induce in-role and extra-role behaviors that drive organizational change and growth. The present study debunks the assumptions of this common M&A practice, providing quantitative evidence that shared vision and autonomous motivation are far more effective drivers of managerial performance than financial incentives.

  2. Optimization of Hierarchical System for Data Acquisition

    Directory of Open Access Journals (Sweden)

    V. Novotny

    2011-04-01

    Full Text Available Television broadcasting over IP networks (IPTV is one of a number of network applications that are except of media distribution also interested in data acquisition from group of information resources of variable size. IP-TV uses Real-time Transport Protocol (RTP protocol for media streaming and RTP Control Protocol (RTCP protocol for session quality feedback. Other applications, for example sensor networks, have data acquisition as the main task. Current solutions have mostly problem with scalability - how to collect and process information from large amount of end nodes quickly and effectively? The article deals with optimization of hierarchical system of data acquisition. Problem is mathematically described, delay minima are searched and results are proved by simulations.

  3. A Lossless Network for Data Acquisition

    CERN Document Server

    AUTHOR|(SzGeCERN)698154; The ATLAS collaboration; Lehmann Miotto, Giovanna

    2016-01-01

    The planned upgrades of the experiments at the Large Hadron Collider at CERN will require higher bandwidth networks for their data acquisition systems. The network congestion problem arising from the bursty many-to-one communication pattern, typical for these systems, will become more demanding. It is questionable whether commodity TCP/IP and Ethernet technologies in their current form will be still able to effectively adapt to the bursty traffic without losing packets due to the scarcity of buffers in the networking hardware. We continue our study of the idea of lossless switching in software running on commercial-off-the-shelf servers for data acquisition systems, using the ATLAS experiment as a case study. The flexibility of design in software, performance of modern computer platforms, and buffering capabilities constrained solely by the amount of DRAM memory are a strong basis for building a network dedicated to data acquisition with commodity hardware, which can provide reliable transport in congested co...

  4. Acquisition of Opposites and Cognitive Explanation

    Directory of Open Access Journals (Sweden)

    Xudong Sun

    2004-12-01

    Full Text Available This paper presents an analysis of the acquisition sequence of two pairs of contrasting terms in English. The research is based on questionnaires completed by Chinese learners of English of various levels. The analysis concludes that easily-recognisable, unmarked, high-frequency terms, from which are derived concepts and terms that express an earlier stage of an action, tend to be easier to learn and enjoy a higher retention level during the first phase of acquisition while those terms which do not share these characteristics have a much lower retention level during the same stage. Given these conclusions, this study suggests that learners and teachers of a language should pay more attention to those terms which are in an unfavourable position in the vocabulary acquisition sequence of a language. (English text.

  5. The data acquisition system of ICT

    International Nuclear Information System (INIS)

    Gao Fuqiang; An Kang; Lu Hua; Cao Peng; Jiang Renqing; Gao Fubing

    2008-01-01

    The purpose of the design is to develop a data acquisition system which can be used to collect and transmit hundreds of channels of weak light signal data at the same time, so as to meet the need of industrial computer tomography. The system is composed of two parts, detection circuit and acquisition circuit. FPGA and 20 bit integral and conversion chips are the primary chips adopted in detection circuit, while the primary chips for acquisition circuit are FPGA and AMCCS5335. The problems, data jam-up and data drop were solved by using multilevel memorizer. A large number of experiments have proved that this system has very high precision and transmission reliability. The design has been applied in several industrial computer tomography machines produced by the industrial computer tomography research center of Chongqing University, and its effectiveness is well apprised. (authors)

  6. Hunger promotes acquisition of nonfood objects.

    Science.gov (United States)

    Xu, Alison Jing; Schwarz, Norbert; Wyer, Robert S

    2015-03-03

    Hunger motivates people to consume food, for which finding and acquiring food is a prerequisite. We test whether the acquisition component spills over to nonfood objects: Are hungry people more likely to acquire objects that cannot satisfy their hunger? Five laboratory and field studies show that hunger increases the accessibility of acquisition-related concepts and the intention to acquire not only food but also nonfood objects. Moreover, people act on this intention and acquire more nonfood objects (e.g., binder clips) when they are hungry, both when these items are freely available and when they must be paid for. However, hunger does not influence how much they like nonfood objects. We conclude that a basic biologically based motivation can affect substantively unrelated behaviors that cannot satisfy the motivation. This presumably occurs because hunger renders acquisition-related concepts and behaviors more accessible, which influences decisions in situations to which they can be applied.

  7. An original approach to data acquisition CHADAC

    CERN Document Server

    CERN. Geneva

    1981-01-01

    Many labs try to boost existing data acquisition systems by inserting high performance intelligent devices in the important nodes of the system's structure. This strategy finds its limits in the system's architecture. The CHADAC project proposes a simple and efficient solution to this problem, using a multiprocessor modular architecture. CHADAC main features are: parallel acquisition of data; CHADAC is fast, it dedicates one processor per branch and each processor can read and store one 16 bit word in 800 ns; original structure; each processor can work in its own private memory, in its own shared memory (double access) and in the shared memory of any other processor. Simple and fast communications between processors are also provided by local DMAs; flexibility; each processor is autonomous and may be used as an independent acquisition system for a branch, by connecting local peripherals to it. Adjunction of fast trigger logic is possible. By its architecture and performances, CHADAC is designed to provide a g...

  8. The importance of partnerships, mergers and acquisitions

    Energy Technology Data Exchange (ETDEWEB)

    Trabandt, C.A. [Merrill Lynch, New York, NY (United States)

    1998-09-01

    An overview of the electric utility industry was presented. The main factors driving mergers and acquisitions in the industry were identified as being consolidation, disaggregation, convergence and international expansion. To prove the point, statistics from recent merger and acquisition transactions in the U.S. were presented. The importance of disaggregation of the utility business and convergence as the major themes of the electricity and natural gas industries were demonstrated. They are driven by a new competitive marketplace and fewer regulations. The driving forces behind them were explained, buttressing the arguments with recent statistics reflecting an upsurge in convergence transactions. Significant opportunities abroad and recent foreign acquisitions by U. S. utilities were also reviewed. With regard to convergence, it was shown to be occurring in both the generation/wholesale and distribution/retail marketing segment of the electric power industry. 3 figs.

  9. Do Strategic Alliances, Acquisitions, and R

    Directory of Open Access Journals (Sweden)

    Martynov Aleksey

    2016-01-01

    Full Text Available This paper studies possible complementarities and substitution effects between such strategic choices as alliances, acquisitions and internal R&D investments. The findings indicate that a firm’s absorptive capacity affects the presence of complementarities and substitution effects among those strategic choices. Firms with high absorptive capacity exhibit substitution effects between alliances and acquisitions and between alliances and internal R&D investments. Firms with high absorptive capacity also exhibit complementarities between acquisitions and additional R&D investments. These results were obtained from panel data of large and medium U.S. companies spanning the years 1998-2009. The results are robust to the use of different measures of performance: profitability, market-to-book value, and sales growth. This paper contributes to our understanding of the role of absorptive capacity for the optimal choice of inter-organizational strategy vs. greater internal R&D investments.

  10. MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells.

    Science.gov (United States)

    Di Fiore, Riccardo; Drago-Ferrante, Rosa; Pentimalli, Francesca; Di Marzo, Domenico; Forte, Iris Maria; D'Anneo, Antonella; Carlisi, Daniela; De Blasio, Anna; Giuliano, Michela; Tesoriere, Giovanni; Giordano, Antonio; Vento, Renza

    2014-11-01

    Osteosarcoma (OS) is the most common type of bone cancer, with a peak incidence in the early childhood. Emerging evidence suggests that treatments targeting cancer stem cells (CSCs) within a tumor can halt cancer and improve patient survival. MicroRNAs (miRNAs) have been implicated in the maintenance of the CSC phenotype, thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Downregulation of miRNA-29 family members (miR-29a/b/c; miR‑29s) was observed in human OS, however, little is known about the functions of miR-29s in human OS CSCs. Previously, during the characterization of 3AB-OS cells, a CSC line selected from human OS MG63 cells, we showed a potent downregulation of miR-29b. In this study, after stable transfection of 3AB-OS cells with miR-29b-1, we investigated the role of miR-29b-1 in regulating cell proliferation, sarcosphere-forming ability, clonogenic growth, chemosensitivity, migration and invasive ability of 3AB-OS cells, in vitro. We found that, miR-29b-1 overexpression consistently reduced both, 3AB-OS CSCs growth in two- and three-dimensional culture systems and their sarcosphere- and colony-forming ability. In addition, while miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis, it did not influence their migratory and invasive capacities, thus suggesting a context-depending role of miR-29b-1. Using publicly available databases, we proceeded to identify potential miR-29b target genes, known to play a role in the above reported functions. Among these targets we analyzed CD133, N-Myc, CCND2, E2F1 and E2F2, Bcl-2 and IAP-2. We also analyzed the most important stemness markers as Oct3/4, Sox2 and Nanog. Real-time RT-PCR and western-blot analyses showed that miR-29b-1 negatively regulated the expression of these markers. Overall, the results show that miR-29b-1 suppresses stemness properties of 3AB-OS CSCs and suggest that developing miR-29b-1 as a novel

  11. LAMPF nuclear chemistry data acquisition system

    International Nuclear Information System (INIS)

    Giesler, G.C.

    1983-01-01

    The LAMPF Nuclear Chemistry Data Acquisition System (DAS) is designed to provide both real-time control of data acquisition and facilities for data processing for a large variety of users. It consists of a PDP-11/44 connected to a parallel CAMAC branch highway as well as to a large number of peripherals. The various types of radiation counters and spectrometers and their connections to the system will be described. Also discussed will be the various methods of connection considered and their advantages and disadvantages. The operation of the system from the standpoint of both hardware and software will be described as well as plans for the future

  12. New data acquisition system for AMS

    Energy Technology Data Exchange (ETDEWEB)

    Pfenninger, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-09-01

    A new data acquisition system based on a VME front-end computer, a Sun workstation and a PC has been installed. It is used for the acquisition of mainly AMS data, their graphical display, and storage of the data in a Oracle database. The measurement of magazines of 25 sample each is fully automated. Several data parameters such as transmission are regularly checked. In case of problems the operator is informed by optical and/or acoustical signals. Screens are updated automatically after every measurement cycle. (author) 1 fig.

  13. The Differences between Emergentism & Skill Acquisition Theory

    Directory of Open Access Journals (Sweden)

    Naeemeh Kharaghani

    2017-01-01

    Full Text Available Although both emergentism and skill acquisition theory developed in the same field (cognitive theories and as an attempt to replace Universal grammar-based approaches, there are some differences between these two theories. The differences lie under their different models of knowledge representation and their diverse degree of emphasis on the role of input. In addition, skill acquisition considers the process of learning while emergentism considers input and output, and what goes on in between has not been considered. Finally it should be mentioned that these two theories take different views towards the learning process. 

  14. Biotech Business Lessons for Defense Acquisition

    Science.gov (United States)

    2016-01-01

    repudiates what func- tional personnel hold dear—that their hurdles are vital to some moral or ethical responsibility to protect or safeguard...94 Strategic Studies Quarterly ♦ Summer 2016 Biotech Business Lessons for Defense Acquisition Col David L. Peeler Jr., USAF Abstract The desire to...examples and lessons from private business sectors would serve DOD interests well. ✵ ✵ ✵ ✵ ✵ Acquisition reform! No other two words so stress or trouble

  15. Data acquisition system for LHCb calorimeter

    International Nuclear Information System (INIS)

    Dai Gang; Gong Guanghua; Shao Beibei

    2007-01-01

    LHCb Calorimeter system is mainly used to identify and measure the energy of the photon, electron, hadron produced by the collision of proton. TELL1 is a common data acquisition platform based on FPGA for LHCb experiment. It is used to adopt custom data acquisition and process method for every detector and provide the data standard for the CPU matrix. This paper provides a novel DAQ and data process model in VHDL for Calorimeter. According to this model. We have built an effective Calorimeter DAQ system, which would be used in LHCb Experiment. (authors)

  16. Architecture of an acquisition system-multiprocessors

    International Nuclear Information System (INIS)

    Postec, H.

    1987-07-01

    To follow the huge increasing of concerned parameters in nuclear detection systems, acquisition systems become bigger and have to present very good rapidity performance. At Ganil, four detection systems have been set in Nautilus reaction chamber, that lead to experiment configurations with 700 parameters to process. In front of present acquisition system limitation, a device more relevant to lecture of a large number of channels show off necessary. Functionalities already operating in other systems and hardware already used have been chosen; specific technical solutions were aldo developed to use the most recent techniques and to take in account the four detection system structure of the device [fr

  17. Modulated Acquisition of Spatial Distortion Maps

    Directory of Open Access Journals (Sweden)

    Aleš Švigelj

    2013-08-01

    Full Text Available This work discusses a novel approach to image acquisition which improves the robustness of captured data required for 3D range measurements. By applying a pseudo-random code modulation to sequential acquisition of projected patterns the impact of environmental factors such as ambient light and mutual interference is significantly reduced. The proposed concept has been proven with an experimental range sensor based on the laser triangulation principle. The proposed design can potentially enhance the use of this principle to a variety of outdoor applications, such as autonomous vehicles, pedestrians’ safety, collision avoidance, and many other tasks, where robust real-time distance detection in real world environment is crucial.

  18. Modulated acquisition of spatial distortion maps.

    Science.gov (United States)

    Volkov, Alexey; Gros, Jerneja Zganec; Zganec, Mario; Javornik, Tomaž; Svigelj, Aleš

    2013-08-21

    This work discusses a novel approach to image acquisition which improves the robustness of captured data required for 3D range measurements. By applying a pseudo-random code modulation to sequential acquisition of projected patterns the impact of environmental factors such as ambient light and mutual interference is significantly reduced. The proposed concept has been proven with an experimental range sensor based on the laser triangulation principle. The proposed design can potentially enhance the use of this principle to a variety of outdoor applications, such as autonomous vehicles, pedestrians' safety, collision avoidance, and many other tasks, where robust real-time distance detection in real world environment is crucial.

  19. Foreign acquisition, plant survival, and employment growth

    DEFF Research Database (Denmark)

    Bandick, Roger; Görg, Holger

    This paper analyses the effect of foreign acquisition on survival probability and employment growth of target plant using data on Swedish manufacturing plants during the period 1993-2002.  An improvement over previous studies is that we take into account firm level heterogeneity by separating...... the lifetime of the acquired plants only if the plant was an exporter.  The effect differs depending on whether the acquisition is horizontal or vertical.  We also find robust positive employment growth effects only for exporters, and only if the takeover is vertical, not horizontal....

  20. Greenfields and acquisitions: a comparative analysis

    Directory of Open Access Journals (Sweden)

    Nicolae MARINESCU

    2016-07-01

    Full Text Available This paper compares greenfields and acquisitions as foreign direct investment (FDI alternatives used by transnational corporations (TNCs. First, the determinants leading to the choice of companies between the two modes of entry into a foreign market are laid out. Then, specific features of each alternative are highlighted, by contrasting the advantages and disadvantages of both types of FDI. Based on this analysis, some conclusions are drawn in the end concerning the most important factors that influence the decision of a company whether to choose a greenfield investment or an acquisition.