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.

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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.

SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells

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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.

Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells.

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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.

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

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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

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

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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

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

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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

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 ...

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

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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.

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

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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.

Chemoresistive gas sensor

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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.

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

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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

Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

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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

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

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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.

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

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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

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

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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.

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

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

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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.

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

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

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 ...

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

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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.

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

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

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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.

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

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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.

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

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

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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...

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

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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.

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

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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

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

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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).

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)

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.

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 ...

Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

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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.

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

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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

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

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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

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

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

[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.

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

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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

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

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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.

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

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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.

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

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

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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.

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

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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

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

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

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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...

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.

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)

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...

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

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

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.

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.

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.

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.

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

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...

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.

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

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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.

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

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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.

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

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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…

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

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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.

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

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

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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

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

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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.

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

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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.

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

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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.

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.

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

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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.

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.

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

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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.

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.

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.

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

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....

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).

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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

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

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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.

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

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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.

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 ...

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

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.

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

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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

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

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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.

Schizophrenia and second language acquisition.

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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.

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

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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.

Concept Acquisition and Experiential Change

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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.

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

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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.

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.

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

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Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China); Xia, Qiang, E-mail: xiaqiang1@yahoo.com.cn [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China)

2012-07-13

Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer 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.

Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

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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.

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

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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.

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)

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...

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.

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.

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

Success Factors of the Companies Mergers and Acquisitions

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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.

[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.

MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

Science.gov (United States)

Lai, Xin; Gupta, Shailendra K; Schmitz, Ulf; Marquardt, Stephan; Knoll, Susanne; Spitschak, Alf; Wolkenhauer, Olaf; Pützer, Brigitte M; Vera, Julio

2018-01-01

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells. The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance. PMID:29464002

GSH-targeted nanosponges increase doxorubicin-induced toxicity "in vitro" and "in vivo" in cancer cells with high antioxidant defenses.

Science.gov (United States)

Daga, Martina; Ullio, Chiara; Argenziano, Monica; Dianzani, Chiara; Cavalli, Roberta; Trotta, Francesco; Ferretti, Carlo; Zara, Gian Paolo; Gigliotti, Casimiro L; Ciamporcero, Eric S; Pettazzoni, Piergiorgio; Corti, Denise; Pizzimenti, Stefania; Barrera, Giuseppina

2016-08-01

Several reports indicate that chemo-resistant cancer cells become highly adapted to intrinsic oxidative stress by up-regulating their antioxidant systems, which causes an increase of intracellular GSH content. Doxorubicin is one of the most widely used drugs for tumor treatment, able to kill cancer cells through several mechanisms. However, doxorubicin use is limited by its toxicity and cancer resistance. Therefore, new therapeutic strategies able to reduce doses and to overcome chemo-resistance are needed. A new class of glutathione-responsive cyclodextrin nanosponges (GSH-NS), is able to release anticancer drugs preferentially in cells having high GSH content. Doxorubicin-loaded GSH-NS, in the cancer cells with high GSH content, inhibited clonogenic growth, cell viability, topoisomerase II activity and induced DNA damage with higher effectiveness than free drug. Moreover, GSH-NS reduced the development of human tumor in xenograft models more than free drug. These characteristics indicate that GSH-NS can be a suitable drug delivery carrier for future applications in cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

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).

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....

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.

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

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.

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...

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

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...

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.

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

OpenAIRE

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

2014-01-01

Background: 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. Methods: 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 immunohistoche...

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

Bee venom suppresses methamphetamine-induced conditioned place preference in mice.

Science.gov (United States)

Kwon, Young Bae; Li, Jing; Kook, Ji Ae; Kim, Tae Wan; Jeong, Young Chan; Son, Ji Seon; Lee, Hyejung; Kim, Kee Won; Lee, Jang Hern

2010-02-01

Although acupuncture is most commonly used for its analgesic effect, it has also been used to treat various drug addictions including cocaine and morphine in humans. This study was designed to investigate the effect of bee venom injection on methamphetamine-induced addictive behaviors including conditioned place preference and hyperlocomotion in mice. Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the acquisition of addictive behaviors was assessed on day 7. After confirming extinction of addictive behaviors on day 17, addictive behaviors reinstated by priming dose of methamphetamine (0.1 mg/kg) was evaluated on day 18. Bee venom (20 microl of 1 mg/ml in saline) was injected to the acupuncture point ST36 on days 1, 3 and 5. Repeated bee venom injections completely blocked development of methamphetamine-induced acquisition and subsequent reinstatement. Single bee venom acupuncture 30 minutes before acquisition and reinstatement test completely inhibited methamphetamine-induced acquisition and reinstatement. Repeated bee venom acupunctures from day 8 to day 12 after methamphetamine-induced acquisition partially but significantly suppressed reinstatement. These findings suggest that bee venom acupuncture has a preventive and therapeutic effect on methamphetamine-induced addiction.

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.)

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.

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.

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…

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....

State-dependent interaction in the antihistamine-induced disruption of a radiation-induced conditioned taste aversion

International Nuclear Information System (INIS)

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

1982-01-01

Two experiments were run to evaluate the possibility that injection of antihistamine can produce a state-dependent acquisition of a radiation-induced conditioned taste aversion. In the first experiment, pretreating rats with the antihistamine chlorpheniramine maleate prior to their initial exposure to sucrose and to low-level irradiation on the conditioning day did not prevent the acquisition of a taste aversion to sucrose when the antihistamine was also administered prior to a subsequent preference test. In the second experiment, rats were both conditioned and tested for a radiation-induced aversion in a drug-free state. Under these condtions, the rats continued to show an aversion to sucrose despite pretreating them with chlorpheniramine prior to irradiation. Since rats conditioned under the antihistamine do not show the radiation-induced conditioned taste aversion when tested for sucrose preference in a nondrug state, it would seem that pretreating rats with an antihistamine prior to conditioning affects only the retrieval of the previously learned response and not its acquisition

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.

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.

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.

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...

Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem-like cells via induction of lncRNA HOTAIR

Science.gov (United States)

Wang, Li; Dong, Ping; Wang, Weiguo; Huang, Mingquan; Tian, Bole

2017-01-01

Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem-like cells (CSCs) and their critical roles in drug resistance, invasion and metastasis, which are tightly regulated by long non-coding RNAs (lncRNAs). The present study demonstrated that HOX antisense intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line PANC-1 and its enriched CSC sub-population. However, after gemcitabine treatment, the expression levels of HOTAIR in CSCs were induced, but not in PANC-1 cells. HOTAIR induced by gemcitabine failed to cause chemoresistance, but promoted the clonogenicity, proliferation and migration of the cells. By introducing HOTAIR using lentivirus, chemoresistance was induced and the self-renewal capacity, proliferation and migration were significantly promoted. By contrast, HOTAIR knockdown in PANC-1 CSCs treated with or without gemcitabine decreased the cell proliferation, altered the cell cycle progression and induced apoptosis, demonstrating its critical roles in regulating the malignant character of PANC-1 CSCs. In conclusion, the present study demonstrated that HOTAIR may be induced by gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and promoting the self-renewal capacity, proliferation and migration of PANC-1 CSCs, which supports its potential application as a novel therapeutic approach for pancreatic cancer. PMID:29201179

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...

Interaction between harmane, a class of β-carboline alkaloids, and the CA1 serotonergic system in modulation of memory acquisition.

Science.gov (United States)

Nasehi, Mohammad; Ghadimi, Fatemeh; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2017-09-01

This study set to assess the involvement of dorsal hippocampus (CA1) serotonergic system on harmane induced memory acquisition deficit. We used one trial step-down inhibitory avoidancetask to evaluate memory retention and then, open field test to evaluate locomotor activity in adult male NMRI mice. The results showed that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) induced impairment of memory acquisition. Pre-training intra-CA1 administration of 5-HT1B/1D receptor agonist (CP94253; 0.5 and 5ng/mouse) and 5-HT2A/2B/2C receptor agonist (α-methyl 5-HT; 50ng/mouse) impaired memory acquisition. Furthermore, intra-CA1 administration of 5-HT1B/1D receptor antagonist (GR127935; 0.5ng/mouse) and 5-HT2 receptor antagonist (cinancerine; 5ng/mouse) improved memory acquisition. In addition, pre-training intra-CA1 injection of sub-threshold dose of CP94253 (0.05ng/mouse) and α-methyl 5-HT (5ng/mouse) potentiated impairment of memory acquisition induced by harmane (12mg/kg, i.p.). On the other hand, pre-training intra-CA1 infusion of sub-threshold dose of GR127935 (0.05ng/mouse) and cinancerine (0.5ng/mouse) with the administration of harmane (12mg/kg, i.p.) weakened impairment of memory acquisition. Moreover, all above doses of drugs did not change locomotor activity. The present findings suggest that there is an interaction between harmane and the CA1 serotonergic system in modulation of memory acquisition. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer.

Science.gov (United States)

Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

2018-05-01

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined. Results: Different proportions of α2δ1 + cells were identified in SCLC cell lines and PDX models. α2δ1 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1 + cells instead of CD133 + cells in PDXs, and an increased proportion of α2δ1 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148-58. ©2018 AACR . ©2018 American Association for Cancer Research.

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…

Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells.

Science.gov (United States)

Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Toro, Lenka; Durinikova, Erika; Tyciakova, Silvia; Demkova, Lucia; Gursky, Jan; Kucerova, Lucia

2016-01-12

Cells of the tumor microenvironment are recognized as important determinants of the tumor biology. The adjacent non-malignant cells can regulate drug responses of the cancer cells by secreted paracrine factors and direct interactions with tumor cells. Human mesenchymal stromal cells (MSC) actively contribute to tumor microenvironment. Here we focused on their response to chemotherapy as during the treatment these cells become affected. We have shown that the secretory phenotype and behavior of mesenchymal stromal cells influenced by cisplatin differs from the naïve MSC. MSC were more resistant to the concentrations of cisplatin, which was cytotoxic for tumor cells. They did not undergo apoptosis, but a part of MSC population underwent senescence. However, MSC pretreatment with cisplatin led to changes in phosphorylation profiles of many kinases and also increased secretion of IL-6 and IL-8 cytokines. These changes in cytokine and phosphorylation profile of MSC led to increased chemoresistance and stemness of breast cancer cells. Taken together here we suggest that the exposure of the chemoresistant cells in the tumor microenvironment leads to substantial alterations and might lead to promotion of acquired microenvironment-mediated chemoresistance and stemness.

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...

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

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.)

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)

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)

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)

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)

Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells

Directory of Open Access Journals (Sweden)

Manel B. Hammouda

2016-07-01

Full Text Available Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK phosphorylation and microphthalmia-associated transcription factor (MITF overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF, BCL-2-associated X protein (BAX and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2. It generated a distinct response in reactive oxygen species (ROS generation and p53 levels depending on the p53 cell line status (wild type or mutant. Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma.

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...

Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

National Research Council Canada - National Science Library

Behbakht, Kian

2008-01-01

.... TRAIL therapies are particularly exciting because TRAIL reverses chemoresistance to standard chemotherapy as well as having a direct growth inhibitory effect on ovarian cancer cells, while sparing normal...

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...

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.

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.

Evaluation of Radiation Response and Gold Nanoparticle Enhancement in Drug-Resistant Pancreatic Cancer Cells

Science.gov (United States)

Abourabia, Assya

Pancreatic cancer is a major cause of cancer-related death worldwide after lung cancer and colorectal cancer Pancreatic treatment modalities consist of surgery, chemotherapy, and radiation therapy or combination of these therapies. These modalities are good to some extents but they do have some limitations. For example, during the chemotherapy, tumor cells can develop some escape mechanisms and become chemoresistant to protect themselves against the chemo drugs and pass on theses escape mechanisms to their offspring, despite the treatment given. Cancer Cells can become chemoresistant by many mechanisms, for example, decreased drug influx mechanisms, decreased of drug transport molecules, decreased drug activation, altered drug metabolism that diminishes the capacity of cytotoxic drugs, and enhanced repair of DNA damage. Given that some of these chemoresistance mechanisms may impact sensitivity to radiation. Therefore, there is a strong need for a new alternative treatment option to amplify the therapeutic efficacy of radiotherapy and eventually increase the overall efficacy of cancer treatment. Nano-radiation therapy is an emerging and promising modality aims to enhance the therapeutic efficacy of radiotherapy through the use of radiosensitizing nanoparticles. The primary goal of using GNP-enhanced radiation is that GNPs are potent radiosensitizer agents that sensitize the tumor cells to radiation, and these agents promote generation of the free radicals produced by Photo- and Auger- electrons emission at the molecular level which can enhance the effectiveness of radiation-induced cancer cell death. The main aim of this research is to analyze and compare the response to radiation of pancreatic cancer cells, PANC-1, and PANC-1 cells that are resistant to oxaliplatin, PANC-1/OR, and investigate the radiation dose enhancement effect attributable to GNP when irradiating the cells with low-energy (220 kVp) beam at various doses. Based on evidence from the existing

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.

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

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.

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

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...

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...

Effects of cannabinoid CB₁ receptor antagonist rimonabant on acquisition and reinstatement of psychostimulant reward memory in mice.

Science.gov (United States)

Yu, Lu-Lu; Zhou, Shuang-Jiang; Wang, Xue-Yi; Liu, Jian-Feng; Xue, Yan-Xue; Jiang, Wengao; Lu, Lin

2011-02-02

Drug addiction processes are considered to be mainly controlled by the mesocorticolimbic dopamine system. Cannabinoids, a class of psychoactive drugs of abuse, elicit their rewarding and pharmacological effects through the endocannabinoid system. Previous research has indicated that dopaminergic neurons in the mesocorticolimbic system are also under the control of the endocannabinoid system. Recently, evidence has suggested that the endocannabinoid system may also participate in the modulation of the common reward system. The present study examined whether rimonabant, a cannabinoid CB₁ receptor antagonist, disrupts the acquisition and reinstatement of psychostimulant reward memory measured by conditioned place preference (CPP). Mice were trained to acquire methamphetamine or cocaine-induced CPP. A priming injection of methamphetamine (0.5 mg/kg, i.p.) or cocaine (5 mg/kg, i.p.) was respectively given to reinstate methamphetamine or cocaine-induced CPP after extinction. Vehicle or rimonabant (1 or 3 mg/kg, i.p.) was administered at different time-points: 30 min before each CPP training session (acquisition) or 30 min before the priming injection (reinstatement). Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the acquisition of methamphetamine- and cocaine-induced CPP. At the high dose (3 mg/kg), rimonabant disrupted the reinstatement of extinguished methamphetamine- or cocaine-induced CPP. These findings indicate that cannabinoid CB₁ receptors play a major role in psychostimulant reward memory, and rimonabant may be a potential pharmacotherapy for psychostimulant addiction. Copyright © 2010. Published by Elsevier B.V.

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...

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...

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...

Age of Acquisition Effects in Chinese EFL learners’ Delexicalized Verb and Collocation Acquisition

Directory of Open Access Journals (Sweden)

Miao Haiyan

2015-05-01

Full Text Available This paper investigates age of acquisition (AoA effects and the acquisition of delexicalized verbs and collocations in Chinese EFL learners, and explores the underlying reasons from the connectionist model for these learners’ acquisition characteristics. The data were collected through a translation test consisted of delexialized verb information section and English-Chinese and Chinese-English collocation parts, aiming to focus on Chinese EFL learners’ receptive and productive abilities respectively. As Chinese EFL is a nationally classroom-based practice beginning from early primary school, the pedagogical value and different phases of acquisition are thus taken into consideration in designing the translation test. Research results show that the effects of AoA are significant not only in the learners’ acquisition of individual delexicalized verbs but also in delexicalized collocations. Although learners have long begun to learn delexicalized verbs, their production indicates that early learning does not guarantee total acquisition, because their grasp of delexicalized verbs still stay at the senior middle school level. AoA effects significantly affect the recognition but not the production of collocations. Furthermore, a plateau effect occurs in learners’ acquisition of college-level delexicalized collocations, as their recognition and production have no processing advantages over earlier learned collocations.

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...

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...

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.

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.

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...

[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.

Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

Directory of Open Access Journals (Sweden)

Yao Fong

2012-05-01

Full Text Available Caffeic acid (CA, a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC₅₀ dose of paclitaxel (PTX, an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls.

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...

NMDA receptor glycine modulatory site in the ventral tegmental area regulates the acquisition, retrieval, and reconsolidation of cocaine reward memory.

Science.gov (United States)

Zhou, Shuang-jiang; Xue, Li-fen; Wang, Xue-yi; Jiang, Wen-gao; Xue, Yan-xue; Liu, Jian-feng; He, Yin-yin; Luo, Yi-xiao; Lu, Lin

2012-05-01

Accumulating clinical and preclinical studies have shown that the memories of the rewarding effects of drugs and their paired cues may contribute to relapse and persistent cocaine use. Glutaminergic actions in the ventral tegmental area (VTA) have been shown to regulate the rewarding effect of drugs and conditioned responses to drug-associated cues, but the role of the VTA in the acquisition, retrieval, and reconsolidation of cocaine cues is not yet known. In the present study, we used 7-chlorothiokynurenic acid (7-CTKA), an N-methyl-D-aspartate (NMDA) receptor glycine modulatory site antagonist with no rewarding effects, to examine the role of the NMDA receptor glycine modulatory site in the acquisition, retrieval, and reconsolidation of cocaine-related reward memory using the conditioned place preference (CPP) paradigm. Separate groups of Sprague-Dawley rats were trained to acquire cocaine-induced CPP. Vehicle or 7-CTKA was microinjected into the VTA or substantia nigra (SN) (5 μg/μl) at different time points: 10 min before each CPP training session (acquisition), 10 min before the reactivation of CPP (retrieval), and immediately after the reactivation of CPP (reconsolidation). Cocaine-induced CPP was retested 24 h and 1 and 2 weeks after 7-CTKA administration. 7-CTKA microinjected into the VTA, but not SN, significantly impaired the acquisition, retrieval, and reconsolidation of cocaine-induced CPP without affecting cocaine-induced locomotion. Our findings suggest that the NMDA receptor glycine modulatory site in the VTA plays a major role in cocaine reward memory, and NMDA receptor glycine site antagonists may be potential pharmacotherapies for the management of relapse.

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.

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.

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...

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...

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

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.

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

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.

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...

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...

Role of hypoxia-inducible factor-α in hepatitis-B-virus X protein-mediated MDR1 activation

International Nuclear Information System (INIS)

Han, Hyo-Kyung; Han, Chang Yeob; Cheon, Eun-Pa; Lee, Jaewon; Kang, Keon Wook

2007-01-01

The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1α (HIF-1α) and induced the nuclear translocation of C/EBPβ. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1α siRNA but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1α activation, and suggest HIF-1α for the therapeutic target of HBV-mediated chemoresistance

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

Motion-robust diffusion tensor acquisition at routine 3T magnetic resonance imaging

International Nuclear Information System (INIS)

Yasmin, Hasina; Abe, Osamu; Masutani, Yoshitaka; Hayashi, Naoto; Ohtomo, Kuni; Kabasawa, Hiroyuki; Aoki, Shigeki

2010-01-01

We compared different acquisition and reconstruction methods in phantom and human studies in the clinical setting to validate our hypothesis that optimizing the k-space acquisition and reconstruction method could decrease motion artifacts. Diffusion tensor images of a water phantom were obtained with three table displacement magnitudes: 1 mm, 2 mm, and 3 mm. Images were reconstructed using homodyne and zero-fill reconstruction. Overscanning in 8- and 16-k y lines was tested. We performed visual assessment of the artifacts using reconstructed coronal images and analyzed them with Wilcoxon signed-ranks test both for phantom and human studies. Also, fractional anisotropy (FA) changes between acquisition methods were compared. Artifacts due to smaller displacement (1 and 2 mm) were significantly reduced in 16-k y overscan with zero filling. The Wilcoxon signed-ranks test showed significant differences (P<0.031 for reconstruction methods and P<0.016 for overscanning methods). FA changes were statistically significant (P<0.037; Student's t-test). The Wilcoxon signed-ranks test showed significant reductions (P<0.005) in the human study. Motion-induced artifacts can be reduced by optimizing acquisition and reconstruction methods. The techniques described in this study offer an effective method for robust estimation of diffusion tensor in the presence of motion-related artifactual data points. (author)

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.

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…

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

VPA and MEL induce apoptosis by inhibiting the Nrf2-ARE signaling pathway in TMZ-resistant U251 cells.

Science.gov (United States)

Pan, Hao; Wang, Handong; Jia, Yue; Wang, Qiang; Li, Liwen; Wu, Qi; Chen, Longbang

2017-07-01

Chemoresistance is the primary obstacle to effective treatment of glioblastoma, the most lethal brain tumor. Our previous study demonstrated that Nf-E2 related factor 2 (Nrf2), a traditional cytoprotective transcription factor, was overexpressed in gliomas and promoted malignancy. The present study aimed to investigate the expression levels of Nrf2‑antioxidant response element (ARE) signaling pathway genes in temozolomide (TMZ)‑resistant U251 human glioblastoma cells (U251‑TMZ). Additionally, the effect of valproic acid (VPA) and melatonin (MEL) on Nrf2 expression in U251‑TMZ cells and their association with chemoresistance was investigated. The results of the present study indicated that the expression levels of components of the Nrf2‑ARE signaling pathway were increased in U251‑TMZ cells compared with U251 parent cells. Silencing of Nrf2 by transfection with small interfering RNA restored the chemosensitivity of U251‑TMZ cells. The Nrf2 inhibitors VPA and MEL successfully reduced Nrf2 expression and survival in U251‑TMZ cells treated with TMZ, accompanied by increased reactive oxygen species levels and apoptosis. Therefore, VPA and MEL may be potential chemotherapeutic sensitizers for the treatment of chemoresistant glioblastoma.

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...

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...

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...

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...

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...

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...

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...

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.

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

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.

CLL cells are resistant to smac mimetics because of an inability to form a ripoptosome complex

NARCIS (Netherlands)

Maas, C.; Tromp, J. M.; van Laar, J.; Thijssen, R.; Elias, J. A.; Malara, A.; Krippner-Heidenreich, A.; Silke, J.; van Oers, M. H. J.; Eldering, E.

2013-01-01

In the lymph node (LN) environment, chronic lymphocytic leukemia (CLL) cells display increased NF-κB activity compared with peripheral blood CLL cells, which contributes to chemoresistance. Antagonists of cellular inhibitor of apoptosis proteins (cIAPs) can induce apoptosis in various cancer cells

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...

Industry Relatedness and Post-Acquisition Innovative Performance

DEFF Research Database (Denmark)

Cefis, Elena; Marsili, Orietta; Rigamonti, Damiana

2015-01-01

This paper examines how characteristics of acquiring and acquired firms influence the curvilinear (inverted U-shaped) relationship between relatedness and post-acquisition innovative performance. Using a relatedness index based on industry co-occurrence in a sample of 1,736 Dutch acquisitions, we...... find that acquirer's internal R&D and acquisition experience, and the small size of acquired firms, help to reach a balance between exploration of novelty and exploitation of synergies in unrelated acquisitions, and to achieve higher post-acquisition performance. However, while the acquirer's R......&D increases flexibility in the acquisition process in presence of deviations from the optimal level of relatedness, acquisition experience may enhance rigidities....

Value Creation through Acquisition Strategy: A Study of Volvo’s Acquisition by Geely

Directory of Open Access Journals (Sweden)

Yane Chandera

2012-04-01

Full Text Available This paper examines the value creation on the acquisition of Volvo Car Corp by Zhejiang Geely Holding Group. The acquisition of Volvo by Geely became an interesting topic to discuss since it was the first time in automotive industry that a Chinese company acquired an international company with a considerably high transaction amount. The paper examines the short term value creation using event study to calculate abnormal returns of each company’s stock during the announcement period and measuring the significance of the cumulative abnormal return. The findings are consistent with previous studies over the years which have shown that most acquisitions fail to add value for shareholders in the acquiring company. The paper discusses the broad managerial implications of the findings this paper discussion on marketing aspect after the acquisition by integrating two different brand perceptions.

Value Creation through Acquisition Strategy: A Study of Volvo’s Acquisition by Geely

Directory of Open Access Journals (Sweden)

Yane Chandera

2012-08-01

Full Text Available This paper examines the value creation on the acquisition of Volvo Car Corp by Zhejiang Geely Holding Group. The acquisition of Volvo by Geely became an interesting topic to discuss since it was the first time in automotive industry that a Chinese company acquired an international company with a considerably high transaction amount. The paper examines the short term value creation using event study to calculate abnormal returns of each company’s stock during the announcement period and measuring the significance of the cumulative abnormal return. The findings are consistent with previous studies over the years which have shown that most acquisitions fail to add value for shareholders in the acquiring company. The paper discusses the broad managerial implications of the findings this paper discussion on marketing aspect after the acquisition by integrating two different brand perceptions.

PMS2 expression in epithelial ovarian cancer is posttranslationally regulated by Akt and essential for platinum-induced apoptosis.

Science.gov (United States)

Jia, Jinghui; Wang, Zehua; Cai, Jing; Zhang, Yuan

2016-03-01

Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic malignancies, mainly due to the advanced stage at diagnosis and development of cisplatin resistance. The sensitivity of tumor cells to cisplatin is frequently affected by defect in DNA mismatch repair (MMR), which repairs mispaired DNA sequences and regulates DNA-damage-induced apoptosis. However, the role of postmeiotic segregation increased 2 (PMS2), a member of MMR protein family, in cisplatin resistance remains elusive. In the present study, we demonstrated the frequent deficiency of PMS2 and phosphorylation of Akt in EOC cell lines and tissues. Results of complex immunoprecipitation (co-IP) and protein stability assay indicated that activated Akt could directly bind to PMS2 and cause degradation of PMS2 in EOC cells. In addition, functional experiments revealed that PMS2 was required for cisplatin-induced apoptosis and cell cycle arrest in G2/M phase. These findings provide a novel insight into molecular mechanisms linking MMR with chemoresistance and suggest that stabilization of PMS2 expression may be useful in overcoming the cisplatin resistance in EOC.

Improvement of Sidestream Dark Field Imaging with an Image Acquisition Stabilizer

OpenAIRE

Balestra, Gianmarco M; Bezemer, Rick; Boerma, E Christiaan; Yong, Ze-Yie; Sjauw, Krishan D; Engstrom, Annemarie E; Koopmans, Matty; Ince, Can

2010-01-01

Abstract Background In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging. Methods The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time ...

USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt.

Science.gov (United States)

Zhang, Jing; Luo, Nan; Tian, Yu; Li, Jiazhi; Yang, Xiaozhou; Yin, Huimin; Xiao, Congshu; Sheng, Jie; Li, Yang; Tang, Bo; Li, Rongkuan

2017-04-11

USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy. Silencing USP22 in chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in vitro; suppressed tumorigenic and metastatic capacities in vivo; and inhibited drug resistance-related proteins (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its function through down-regulating PI3K and activating Smad4, which inhibited phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells. Our results, for the first time, provide evidence that USP22 plays a critical role in the development of chemoresistant HCC cells and that high USP22 expression serves as a molecular marker for the prognosis of HCC patients who undergo chemotherapy.

17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

Energy Technology Data Exchange (ETDEWEB)

Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

2016-05-13

17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

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.

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

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

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.

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...

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...

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

Inhibition of p38 MAPK enhances ABT-737-induced cell death in melanoma cell lines: novel regulation of PUMA.

Science.gov (United States)

Keuling, Angela M; Andrew, Susan E; Tron, Victor A

2010-06-01

The mitogen-activated protein kinase (MAPK) pathway is constitutively activated in the majority of melanomas, promoting cell survival, proliferation and migration. In addition, anti-apoptotic Bcl-2 family proteins Mcl-1, Bcl-xL and Bcl-2 are frequently overexpressed, contributing to melanoma's well-documented chemoresistance. Recently, it was reported that the combination of MAPK pathway inhibition by specific MEK inhibitors and Bcl-2 family inhibition by BH3-mimetic ABT-737 synergistically induces apoptotic cell death in melanoma cell lines. Here we provide the first evidence that inhibition of another key MAPK, p38, synergistically induces apoptosis in melanoma cells in combination with ABT-737. We also provide novel mechanistic data demonstrating that inhibition of p38 increases expression of pro-apoptotic Bcl-2 protein PUMA. Furthermore, we demonstrate that PUMA can be cleaved by a caspase-dependent mechanism during apoptosis and identify what appears to be the PUMA cleavage product. Thus, our findings suggest that the combination of ABT-737 and inhibition of p38 is a promising, new treatment strategy that acts through a novel PUMA-dependent mechanism.

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.

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

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...

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...

A hybrid data acquisition system for magnetic measurements of accelerator magnets

International Nuclear Information System (INIS)

Wang, X.; Hafalia, R.; Joseph, J.; Lizarazo, J.; Martchevsky, M.; Sabbi, G.L.

2011-01-01

A hybrid data acquisition system was developed for magnetic measurement of superconducting accelerator magnets at LBNL. It consists of a National Instruments dynamic signal acquisition (DSA) card and two Metrolab fast digital integrator (FDI) cards. The DSA card records the induced voltage signals from the rotating probe while the FDI cards records the flux increment integrated over a certain angular step. This allows the comparison of the measurements performed with two cards. In this note, the setup and test of the system is summarized. With a probe rotating at a speed of 0.5 Hz, the multipole coefficients of two magnets were measured with the hybrid system. The coefficients from the DSA and FDI cards agree with each other, indicating that the numerical integration of the raw voltage acquired by the DSA card is comparable to the performance of the FDI card in the current measurement setup.

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...

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...

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

Directory of Open Access Journals (Sweden)

Miaki Uzu

2015-05-01

Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

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.

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

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)

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…

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

Tenascin-C induces resistance to apoptosis in pancreatic cancer cell through activation of ERK/NF-κB pathway.

Science.gov (United States)

Shi, Meiyan; He, Xiaodan; Wei, Wei; Wang, Juan; Zhang, Ti; Shen, Xiaohong

2015-06-01

As a glycol-protein located in extracellular matrix (ECM), tenascin-C (TNC) is absent in most normal adult tissues but is highly expressed in the majority of malignant solid tumors. Pancreatic cancer is characterized by an abundant fibrous tissue rich in TNC. Although it was reported that TNC's expression increased in the progression from low-grade precursor lesions to invasive cancer and was associated with tumor differentiation in human pancreatic cancer, studies on the relations between TNC and tumor progression in pancreatic cancer were rare. In this study, we performed an analysis to determine the effects of TNC on modulating cell apoptosis and chemo-resistance and explored its mechanisms involving activation in pancreatic cancer cell. The expressions of TNC, ERK1/2/p-ERK1/2, Bcl-xL and Bcl-2 were detected by immunohistochemistry and western blotting. Then the effects of exogenous and endogenous TNC on the regulation of tumor proliferation, apoptosis and gemcitabine cytotoxicity were investigated. The associations among the TNC knockdown, TNC stimulation and expressions of ERK1/2/NF-κB/p65 and apoptotic regulatory proteins were also analyzed in cell lines. The mechanism of TNC on modulating cancer cell apoptosis and drug resistant through activation of ERK1/2/NF-κB/p65 signals was evaluated. The effect of TNC on regulating cell cycle distribution was also tested. TNC, ERK1/2/p-ERK1/2, and apoptotic regulatory proteins Bcl-xL and Bcl-2 were highly expressed in human pancreatic cancer tissues. In vitro, exogenous TNC promoted pancreatic cancer cell growth also mediates basal as well as starved and drug-induced apoptosis in pancreatic cancer cells. The effects of TNC on anti-apoptosis were induced by the activation state of ERK1/2/NF-κB/p65 signals in pancreatic cell. TNC phosphorylate ERK1/2 to induce NF-κB/p65 nucleus translocation. The latter contributes to promote Bcl-xL, Bcl-2 protein expressions and reduce caspase activity, which inhibit cell apoptotic

TET2 functions as a resistance factor against DNA methylation acquisition during Epstein-Barr virus infection.

Science.gov (United States)

Namba-Fukuyo, Hiroe; Funata, Sayaka; Matsusaka, Keisuke; Fukuyo, Masaki; Rahmutulla, Bahityar; Mano, Yasunobu; Fukayama, Masashi; Aburatani, Hiroyuki; Kaneda, Atsushi

2016-12-06

Extensive DNA methylation is observed in gastric cancer with Epstein-Barr virus (EBV) infection, and EBV infection is the cause to induce this extensive hypermethylaton phenotype in gastric epithelial cells. However, some 5' regions of genes do not undergo de novo methylation, despite the induction of methylation in surrounding regions, suggesting the existence of a resistance factor against DNA methylation acquisition. We conducted an RNA-seq analysis of gastric epithelial cells with and without EBV infection and found that TET family genes, especially TET2, were repressed by EBV infection at both mRNA and protein levels. TET2 was found to be downregulated by EBV transcripts, e.g. BARF0 and LMP2A, and also by seven human miRNAs targeting TET2, e.g., miR-93 and miR-29a, which were upregulated by EBV infection, and transfection of which into gastric cells repressed TET2. Hydroxymethylation target genes by TET2 were detected by hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq) with and without TET2 overexpression, and overlapped significantly with methylation target genes in EBV-infected cells. When TET2 was knocked down by shRNA, EBV infection induced de novo methylation more severely, including even higher methylation in methylation-acquired promoters or de novo methylation acquisition in methylation-protected promoters, leading to gene repression. TET2 knockdown alone without EBV infection did not induce de novo DNA methylation. These data suggested that TET2 functions as a resistance factor against DNA methylation in gastric epithelial cells and repression of TET2 contributes to DNA methylation acquisition during EBV infection.

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.

The ROS/SUMO Axis Contributes to the Response of Acute Myeloid Leukemia Cells to Chemotherapeutic Drugs

Directory of Open Access Journals (Sweden)

Guillaume Bossis

2014-06-01

Full Text Available Chemotherapeutic drugs used in the treatment of acute myeloid leukemias (AMLs are thought to induce cancer cell death through the generation of DNA double-strand breaks. Here, we report that one of their early effects is the loss of conjugation of the ubiquitin-like protein SUMO from its targets via reactive oxygen species (ROS-dependent inhibition of the SUMO-conjugating enzymes. Desumoylation regulates the expression of specific genes, such as the proapoptotic gene DDIT3, and helps induce apoptosis in chemosensitive AMLs. In contrast, chemotherapeutics do not activate the ROS/SUMO axis in chemoresistant cells. However, pro-oxidants or inhibition of the SUMO pathway by anacardic acid restores DDIT3 expression and apoptosis in chemoresistant cell lines and patient samples, including leukemic stem cells. Finally, inhibition of the SUMO pathway decreases tumor growth in mice xenografted with AML cells. Thus, targeting the ROS/SUMO axis might constitute a therapeutic strategy for AML patients resistant to conventional chemotherapies.

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...

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)

The role of histamine in estradiol-induced conditioned consumption reductions.

Science.gov (United States)

Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

2005-01-31

Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

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....

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...

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

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....

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

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

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.

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...

Land acquisition problems in China ' adopting land acquisition act 1960 of Malaysia as an alternative procedure

Directory of Open Access Journals (Sweden)

Anuar Alias

2011-06-01

Full Text Available Land is scarce and it is the most important resource that humans rely on. Therefore, the protection of land interests is extremely important. Land acquisition deprives the owner's interest on land. A fair and adequate compensation as well as transparent procedures are crucial for land acquisition. The aims of this study are to investigate the adequacy of compensation for land acquisition in China as compared to the Malaysian framework, and to enhance the understanding of land acquisition procedures and determination of compensation in both China and Malaysia. A case study was conducted to investigate whether the compensation for land acquisition in China is adequate and equitable. Two sets of compensation have been calculated, one based on the current compensation standard executed in China; and the other, calculated based on the market value of the land. The finding reveals that the compensation based on the current compensation standard in China is inadequate. The compensation determined by compensation standard executed varied with the market value of the land. In order to better protect the dispossessed owners in China, the compensation for land acquisition should be based on the market value of the land and other related matters such as betterment, severance, injurious affection, incidental expenses and accommodation works should be given due consideration.

Measuring Acquisition Workforce Quality Through Dynamic Knowledge and Performance: An Exploratory Investigation to Interrelate Acquisition Knowledge with Process Maturity

OpenAIRE

Nissen, Mark E.; Rendon, Rene G.

2013-01-01

Acquisition Research Program Sponsored Report Series Approved for public release; distribution is unlimited. The efficacy of defense acquisition is highly dependent upon acquisition workforce quality, but assessing such quality remains a major challenge, particularly given the knowledge-intensive and dynamic nature of acquisition organizations and processes. Hence, it is difficult to gauge?much less predict?the impact of leadership interventions in terms of policy, process, reg...

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

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.

Science.gov (United States)

Lee, Hye Lim; Park, Mi Hee; Hong, Ji Eun; Kim, Dae Hwan; Kim, Ji Young; Seo, Hyen Ok; Han, Sang-Bae; Yoon, Joo Hee; Lee, Won Hyoung; Song, Ho Sueb; Lee, Ji In; Lee, Ung Soo; Song, Min Jong; Hong, Jin Tae

2016-02-01

We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.

Factors affecting the Long-Term Post-Acquisition Performance of BRICS Firms Engaging in Cross-Border Mergers and Acquisitions

Directory of Open Access Journals (Sweden)

Damilola Oyetade

2017-04-01

Full Text Available The purpose of the paper is to examine factors that affect the long-term performance of listed firms from Brazil, Russia, India, China and South Africa (BRICS that engage in cross-border mergers and acquisitions. This paper adds to the existing literature on the performance of mergers and acquisitions from emerging economies by examining the performance of mergers and acquisitions activities on acquirers from individual BRICS countries and examining whether intra-BRICS acquisitions are more beneficial than non-BRICS acquisitions. The system generalised method of moments estimation technique was employed in order to control for unobservable heterogeneity and potential endogeneity problems using accounting data and merger deal information collected from the Bloomberg online database for the period January 2000 to December 2012.The results obtained indicate that there is persistence in the profits, suggesting that BRICS acquirers continue to profit as they engage in mergers and acquisitions, and firm size significantly impacts the profits of acquirers.

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.

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...

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

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)

The Disintegrin and Metalloprotease ADAM12 Is Associated with TGF-β-Induced Epithelial to Mesenchymal Transition.

Directory of Open Access Journals (Sweden)

Michaël Ruff

Full Text Available The increased expression of the Disintegrin and Metalloprotease ADAM12 has been associated with human cancers, however its role remain unclear. We have previously reported that ADAM12 expression is induced by the transforming growth factor, TGF-β and promotes TGF-β-dependent signaling through interaction with the type II receptor of TGF-β. Here we explore the implication of ADAM12 in TGF-β-mediated epithelial to mesenchymal transition (EMT, a key process in cancer progression. We show that ADAM12 expression is correlated with EMT markers in human breast cancer cell lines and biopsies. Using a non-malignant breast epithelial cell line (MCF10A, we demonstrate that TGF-β-induced EMT increases expression of the membrane-anchored ADAM12L long form. Importantly, ADAM12L overexpression in MCF10A is sufficient to induce loss of cell-cell contact, reorganization of actin cytoskeleton, up-regulation of EMT markers and chemoresistance. These effects are independent of the proteolytic activity but require the cytoplasmic tail and are specific of ADAM12L since overexpression of ADAM12S failed to induce similar changes. We further demonstrate that ADAM12L-dependent EMT is associated with increased phosphorylation of Smad3, Akt and ERK proteins. Conversely, inhibition of TGF-β receptors or ERK activities reverses ADAM12L-induced mesenchymal phenotype. Together our data demonstrate that ADAM12L is associated with EMT and contributes to TGF-β-dependent EMT by favoring both Smad-dependent and Smad-independent pathways.

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

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....

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

48 CFR 1401.370 - Acquisition Managers' Partnership.

Science.gov (United States)

2010-10-01

...' Partnership. 1401.370 Section 1401.370 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... Acquisition Managers' Partnership. (a) The Acquisition Managers' Partnership (AMP) is a forum for DOI's senior... the partnership will meet and develops meeting agendas. The Chairperson will distribute the meeting...

Pattern-based framework for data acquisition systems

International Nuclear Information System (INIS)

Padmini, S.; Diwakar, M.P.; Nair, Preetha; Mathew, R.

2004-01-01

The data acquisition framework implements a reusable abstract architectural design for use in the development of data acquisition systems. The framework is being used to build Flux Mapping system (FMs) for TAPS III-IV and RRS Data Acquisition System for Dhruva reactor

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.)

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.

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...

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...

48 CFR 18.113 - Interagency acquisitions under the Economy Act.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Interagency acquisitions under the Economy Act. 18.113 Section 18.113 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities 18.113 Interagency acquisitions under...

48 CFR 1825.1101 - Acquisition of supplies.

Science.gov (United States)

2010-10-01

....225-8, Duty-Free Entry of Space Articles, in solicitations and contracts when the supplies that will... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Acquisition of supplies... ADMINISTRATION SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Solicitation Provisions and Contract Clauses 1825.1101...

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.

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...

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...

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...

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...

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.

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

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...

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. ...

7 CFR 1735.76 - Acquisition of affiliates.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Acquisition of affiliates. 1735.76 Section 1735.76... AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Acquisitions Involving Loan Funds § 1735.76 Acquisition of affiliates. A borrower shall not use RUS loan funds to acquire...

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis.

Science.gov (United States)

Wang, Xiaoyu; Zhang, Yiting; Lin, Haiyingjie; Liu, Yan; Tan, Yi; Lin, Jie; Gao, Fenze; Lin, Shaoqiang

2017-01-22

Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3. Copyright © 2016 Elsevier Inc. All rights reserved.

War-gaming application for future space systems acquisition: MATLAB implementation of war-gaming acquisition models and simulation results

Science.gov (United States)

Vienhage, Paul; Barcomb, Heather; Marshall, Karel; Black, William A.; Coons, Amanda; Tran, Hien T.; Nguyen, Tien M.; Guillen, Andy T.; Yoh, James; Kizer, Justin; Rogers, Blake A.

2017-05-01

The paper describes the MATLAB (MathWorks) programs that were developed during the REU workshop1 to implement The Aerospace Corporation developed Unified Game-based Acquisition Framework and Advanced Game - based Mathematical Framework (UGAF-AGMF) and its associated War-Gaming Engine (WGE) models. Each game can be played from the perspectives of the Department of Defense Acquisition Authority (DAA) or of an individual contractor (KTR). The programs also implement Aerospace's optimum "Program and Technical Baseline (PTB) and associated acquisition" strategy that combines low Total Ownership Cost (TOC) with innovative designs while still meeting warfighter needs. The paper also describes the Bayesian Acquisition War-Gaming approach using Monte Carlo simulations, a numerical analysis technique to account for uncertainty in decision making, which simulate the PTB development and acquisition processes and will detail the procedure of the implementation and the interactions between the games.

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...

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.

49 CFR 24.102 - Basic acquisition policies.

Science.gov (United States)

2010-10-01

... valuation only if the offer to acquire the property is $10,000, or less. (See appendix A, § 24.102(n).) [70... Transportation Office of the Secretary of Transportation UNIFORM RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Real Property Acquisition § 24.102 Basic acquisition...

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...

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...

Relationship of signal-to-noise ratio with acquisition parameters in MRI for a given contrast

International Nuclear Information System (INIS)

Bittoun, J.; Leroy-Willig, A.; Idy, I.; Halimi, P.; Syrota, A.; Desgrez, A.; Saint-Jalmes, H.

1987-01-01

The signal-to-noise ratio (SNR) is certainly the most important characteristic of medical images, since the spatial resolution and the visualization of contrast are dependent on its value. On the other hand, modifying an acquisition variable in magnetic resonance imaging, in order to improve spatial resolution for example, may induce a SNR loss and finally alter the image quality. We have studied a theoretical relation between SNR and 2DFT method acquisition variables with the exception of parameters such as TR, TE and TI; these parameters are determined by the desired contrast in order to confirm a diagnosis. According to this relation SNR is proportional to each dimension of the slice, and to the square root of the number of averaged signals; it is inversely proportional to the number of frequency points and to the square root of the number of phase points. This relation was experimentally verified with phantoms and on an MR system at 1.5 T. It was then plotted as a multiple-entry graph on which operators at the console can read the number of averaged signals necessary to compensate SNR loss induced by a modification of other parameters [fr

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

Science.gov (United States)

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

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...

Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

International Nuclear Information System (INIS)

Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

2013-01-01

Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

Energy Technology Data Exchange (ETDEWEB)

Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

2013-04-15

Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

The Role of Hippocampal 5HT3 Receptors in Harmaline-Induced Memory Deficit

Directory of Open Access Journals (Sweden)

Mohammad Nasehi

2015-07-01

Full Text Available Introduction: The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic (5-HT system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline.  Methods: Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333 and antagonist (RS23597-190 were injected intra-hippocampal. A single-trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively.  Results: The data revealed that pre-training injection of higher dose of harmaline (1 mg/kg, RS67333 (0.5 ng/mouse and RS23597-190 (0.5 ng/mouse decreased memory acquisition process in the adult mice. Moreover, concurrent pre-training administration of subthreshold dose of RS67333 (0.005 ng/mouse or RS23597-190 (0.005 ng/mouse with subthreshold dose of harmaline (0.5 mg/kg, i.p. intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors.  Discussion: The results demonstrated that the synergistic effect between both hippocampal 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced amnesia.

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)

Changing of the ELAN data acquisition to an integrated system with VME frontend acquisition and VAX work station analysis

International Nuclear Information System (INIS)

Foerster, W.

1991-07-01

A new data acquisition system for the experiment ELAN at the electron stretcher accelerator ELSA had become necessary due to changes in the experimental setup. The data acquisition and analysis which formerly both were performed by a single computer system are now separately done by a VMEbus-Computer and a VAX-Workstation. Based on the software components MECDAS (Mainz Experiment Control and Data Acquisition System) and GOOSY (GSI Online Offline System) a powerfull tool for data acquisition and analysis has been adapted to the requirements of the ELAN experiment. (orig.) [de

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

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...

Foreign acquisitions, domestic multinationals, and R&D

DEFF Research Database (Denmark)

Bandick, Roger; Görg, Holger; Karpaty, Patrik

endogeneity of the acquisition dummy.  Overall, our results give no support to the fears that foreign acquisition of domestic firms lead to a brain drain of R&D activity in Swedish MNEs. Rather, this paper finds robust evidence that foreign acquisitions lead to increasing R&D intensity in acquired domestic......The aim of this paper is to evaluate the causal effect of foreign acquisition on R&D intensity in targeted domestic firms. We are able to distinguish domestic multinationals and non-multinationals, which allows us to investigate the fear that the change in ownership of domestic to foreign...

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

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...

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.

48 CFR 1552.232-74 - Payments-simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... acquisition procedures financing. 1552.232-74 Section 1552.232-74 Federal Acquisition Regulations System... Provisions and Clauses 1552.232-74 Payments—simplified acquisition procedures financing. As prescribed in... acquisition procedures financing. Payments—Simplified Acquisition Procedures Financing (JUN 2006) Simplified...

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.

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%

First and second language acquisition: Towards a reconcillation

Directory of Open Access Journals (Sweden)

Nau Nicole

2015-07-01

Full Text Available For the past two decades, research on first language acquisition on the one side, and on second language acquisition and learning on the other have largely developed separately, probably as a reaction to the failure of earlier attempts to use the same methods or simply transfer insights gained in one of the fields to the other. T his article argues that a reconciliation may be fruitful, provided that different aspects which have often got blurred in the discussion are considered separately. These aspects include the assessment of multilingualism and monolingualism, the age factor and the definition of “first” and “second” language, the understanding of linguistic competence and of completeness of acquisition, different forms of acquisition and learning, and uniformity vs. individual differences in the process of language acquisition. By challenging some widely held views on characteristics of first language acquisition and its differences to second language learning, more fine-grained research questions are revealed, some of which have been addressed in recent studies on language acquisition and multilingualism

Knowledge Capture and Acquisition Mechanisms at Kisii University

Directory of Open Access Journals (Sweden)

Nemwel Aming'a

2015-07-01

Full Text Available Knowledge management and knowledge assets have gained much prominence in recent years and are said to improve organizational performance. Knowledge capture and acquisition mechanisms enhance organizational memory and performance. However, knowledge capture and acquisition mechanisms in higher education institutions are not well known. The aim of this study was to investigate the knowledge capture and acquisition mechanisms at Kisii University. This was a case study in which data were collected through interviews and questionnaires. Purposive sampling was used to determine interview participants while questionnaire respondents were selected through stratified random sampling. Qualitative and quantitative data were analysed using SPSS® student version 14; it revealed that there were various knowledge capture and acquisition mechanisms at Kisii University. It was also established that the University encountered various challenges in knowledge capture and acquisition and lacked some essential knowledge capture and acquisition mechanisms. In this regard, this study proposed knowledge capture and acquisition guidelines that may be adopted by the University to enhance its organizational memory and performance.

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.

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.

Financing and Regulatory Frictions in Mergers and Acquisitions

NARCIS (Netherlands)

Q. Zhang (Quxian)

2018-01-01

markdownabstractThis dissertation studies how financial frictions and regulatory costs affect mergers and acquisitions (M&A). The first conclusion is that financial distress drives firms to make diversifying acquisitions. Acquisitions made by distressed firms in recent years are economically

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

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

Multiple-user data acquisition and analysis system

International Nuclear Information System (INIS)

Manzella, V.; Chrien, R.E.; Gill, R.L.; Liou, H.I.; Stelts, M.L.

1981-01-01

The nuclear physics program at the Brookhaven National Laboratory High Flux Beam Reactor (HFBR) employs a pair of PDP-11 computers for the dual functions of data acquisition and analysis. The data acquisition is accomplished through CAMAC and features a microprogrammed branch driver to accommodate various experimental inputs. The acquisition computer performs the functions of multi-channel analyzers, multiscaling and time-sequenced multichannel analyzers and gamma-ray coincidence analyzers. The data analysis computer is available for rapid processing of data tapes written by the acquisition computer. The ability to accommodate many users is facilitated by separating the data acquisition and analysis functions, and allowing each user to tailor the analysis to the specific requirements of his own experiment. The system is to be upgraded soon by the introduction of a dual port disk to allow a data base to be available to each computer

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....

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

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

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

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

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

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

Predictors of chain acquisition among independent dialysis facilities.

Science.gov (United States)

Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

2010-04-01

To determine the predictors of chain acquisition among independent dialysis providers. Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996-2003. Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status.

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...

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...

Data acquisition for experiments with multi-detector arrays

Indian Academy of Sciences (India)

Experiments with multi-detector arrays have special requirements and place higher demands on computer data acquisition systems. In this contribution we discuss data acquisition systems with special emphasis on multi-detector arrays and in particular we describe a new data acquisition system, AMPS which we have ...

78 FR 18349 - Federal Acquisition Regulation; Information Collection; Commercial Item Acquisitions

Science.gov (United States)

2013-03-26

... information provided. FOR FURTHER INFORMATION CONTACT: Mr. Michael O. Jackson, Procurement Analyst, Office of Governmentwide Acquisition Policy, GSA (202) 208- 4949 or email at michaelo.jackson@gsa.gov . SUPPLEMENTARY...

Actively triggered 4d cone-beam CT acquisition

Energy Technology Data Exchange (ETDEWEB)

Fast, Martin F.; Wisotzky, Eric [German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Oelfke, Uwe; Nill, Simeon [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT (United Kingdom)

2013-09-15

Purpose: 4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this “after-the-fact” binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor.Methods: The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective “Faraday” shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories.Results: With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145

Actively triggered 4d cone-beam CT acquisition.

Science.gov (United States)

Fast, Martin F; Wisotzky, Eric; Oelfke, Uwe; Nill, Simeon

2013-09-01

4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this "after-the-fact" binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor. The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective "Faraday" shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories. With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145 projections were acquired per respiratory

Actively triggered 4d cone-beam CT acquisition

International Nuclear Information System (INIS)

Fast, Martin F.; Wisotzky, Eric; Oelfke, Uwe; Nill, Simeon

2013-01-01

Purpose: 4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this “after-the-fact” binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor.Methods: The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective “Faraday” shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories.Results: With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145

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…

Acquisition by Processing Theory: A Theory of Everything?

Science.gov (United States)

Carroll, Susanne E.

2004-01-01

Truscott and Sharwood Smith (henceforth T&SS) propose a novel theory of language acquisition, "Acquisition by Processing Theory" (APT), designed to account for both first and second language acquisition, monolingual and bilingual speech perception and parsing, and speech production. This is a tall order. Like any theoretically ambitious…

48 CFR 53.212 - Acquisition of commercial items.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Acquisition of commercial... (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.212 Acquisition of commercial items. SF 1449 (Rev. 3/2005), Solicitation/Contract/Order for Commercial Items. SF 1449 is prescribed for use in...

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.

Anti-Leukemic Activity of Shikonin: Role of ERP57 in Shikonin Induced Apoptosis in Acute Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Rachana Trivedi

2016-07-01

Full Text Available Background/Aims: ER-Stress and activation of unfolded protein response belong to the major factors involved in chemoresistance in cancer cells. In this study we investigated the effect of shikonin on the survival of acute myeloid leukemia cells and the role of ER-stress protein ERP57, a protein disulfide isomerase, in improvement of chemotherapy. Methods: Using MTT assay we studied cytotoxic effects of shikonin on HL-60 cells. The flow cytometry was adopted to examine the shikonin induced mode of cell death in HL-60 cells. The overall protein expression alteration resulting from shikonin treatment was investigated using proteomics methods. Western blotting was performed to quantify the alteration in protein expression in HL-60 after shikonin treatment. Silencing and overexpression studies were carried out to highlight the therapeutic role of ERP57 in shikonin effect on AML cells. Results: Shikonin induces apoptosis in HL-60 cells without significant effect on Primary cells from healthy volunteers. The apoptotic effect was dose and time dependent and was accompanied by strong alteration in cell proteome. Among the proteins targeted by shikonin, ERP57 was significantly downregulated in HL-60 after treatment. Compared to healthy control ERP57 was found to be highly expressed in AML cell line HL60 and was downregulated after shikonin treatment. Overexpression of ERP57 protected HL-60 from shikonin induced apoptosis, whereas knockdown of ERP57 expression resulted in increase in shikonin induced apoptosis. Conclusions: Our results demonstrate that ERP57 plays a crucial role in resistance towards shikonin induced apoptosis in AML cells. Targeting of ERP57 might offer a new therapeutic option for the treatment of acute myeloid leukemia.

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…

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...

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.

Improvement of sidestream dark field imaging with an image acquisition stabilizer.

Science.gov (United States)

Balestra, Gianmarco M; Bezemer, Rick; Boerma, E Christiaan; Yong, Ze-Yie; Sjauw, Krishan D; Engstrom, Annemarie E; Koopmans, Matty; Ince, Can

2010-07-13

In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging. The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared. Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 +/- 0.15 N without vs. 0.62 +/- 0.05 N with the IAS, p IAS ensured an increased duration of a stable image sequence (8 +/- 2 s without vs. 42 +/- 8 s with the IAS, p IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 +/- 5 s without vs. 67 +/- 14 s with the IAS, p = 0.006). The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS improved both axial and lateral SDF image stability and thereby increased the critical force required

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...

10 CFR 490.302 - Vehicle acquisition mandate schedule.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Vehicle acquisition mandate schedule. 490.302 Section 490... Alternative Fuel Provider Vehicle Acquisition Mandate § 490.302 Vehicle acquisition mandate schedule. (a) Except as provided in section 490.304 of this part, of the light duty motor vehicles newly acquired by a...

Model-based Sensor Data Acquisition and Management

OpenAIRE

Aggarwal, Charu C.; Sathe, Saket; Papaioannou, Thanasis G.; Jeung, Ho Young; Aberer, Karl

2012-01-01

In recent years, due to the proliferation of sensor networks, there has been a genuine need of researching techniques for sensor data acquisition and management. To this end, a large number of techniques have emerged that advocate model-based sensor data acquisition and management. These techniques use mathematical models for performing various, day-to-day tasks involved in managing sensor data. In this chapter, we survey the state-of-the-art techniques for model-based sensor data acquisition...

Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

Directory of Open Access Journals (Sweden)

Sonja Stojković

2016-06-01

Full Text Available Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl-1-nitrosourea (BCNU and temozolomide (TMZ. Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.

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...

A VMEbus general-purpose data acquisition system

International Nuclear Information System (INIS)

Ninane, A.; Nemry, M.; Martou, J.L.; Somers, F.

1992-01-01

We present a general-purpose, VMEbus based, multiprocessor data acquisition and monitoring system. Events, handled by a master CPU, are kept at the disposal of data storage and monitoring processes which can run on distinct processors. They access either the complete set of data or a fraction of them, minimizing the acquisition dead-time. The system is built with the VxWorks 5.0 real time kernel to which we have added device drivers for data acquisition and monitoring. The acquisition is controlled and the data are displayed on a workstation. The user interface is written in C ++ and re-uses the classes of the Interviews and the NIH libraries. The communication between the control workstation and the VMEbus processors is made through SUN RPCs on an Ethernet link. The system will be used for, CAMAC based, data acquisition for nuclear physics experiments as well as for the VXI data taking with the 4π configuration (100 neutron detectors) of the Brussels-Caen-Louvian-Strasbourg DEMON collaboration. (author)

7 CFR 1710.107 - Amount lent for acquisitions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Amount lent for acquisitions. 1710.107 Section 1710... GUARANTEES Loan Purposes and Basic Policies § 1710.107 Amount lent for acquisitions. The maximum amount that will be lent for an acquisition is limited to the value of the property, as determined by RUS. If the...

Five channel data acquisition system for tracer studies

International Nuclear Information System (INIS)

Narender Reddy, J.; Dhananjay Reddy, Y.; Dheeraj Reddy, J.

2001-01-01

Radioactive tracers are being used by many modern industries for trouble shooting, process control/quality control and optimization in the process plants. A five channel data acquisition system which has five independent scintillation detector based channels for data acquisition has been developed and made available. This system can be used for tracer studies involving Mean residence time, Resident time distribution and other similar parameters involving tracer movement. System developed can acquire data with dwell times ranging from 10 m sec to 100 sec into each channel and has a capacity to acquire data into 10K channels. Each channel electronics, has a 1x1 NaI Scintillation Detector probe, HV, AMP SCA, micro-controller based data acquisition card with independent dot matrix LCD display for visualization. Extensive use of serial bus (I 2 C, microwire) compatible devices has been incorporated in the design. Data acquisition is initiated simultaneously into all the channels. System design permits delayed/prompt data acquisition selectively. Dual counter switching technique has been employed to achieve faster dwell times for data acquisition. (author)

Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.

Science.gov (United States)

Yin, Tao; He, Sisi; Liu, Xiaoling; Jiang, Wei; Ye, Tinghong; Lin, Ziqiang; Sang, Yaxiong; Su, Chao; Wan, Yang; Shen, Guobo; Ma, Xuelei; Yu, Min; Guo, Fuchun; Liu, Yanyang; Li, Ling; Hu, Qiancheng; Wang, Yongsheng; Wei, Yuquan

2015-01-01

Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1β release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance. Copyright © 2014 by The American Association of Immunologists, Inc.

Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

Science.gov (United States)

Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

2015-08-03

Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.

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

75 FR 60261 - Federal Acquisition Regulation; Award-Fee Language Revision

Science.gov (United States)

2010-09-29

...-AL42 Federal Acquisition Regulation; Award-Fee Language Revision AGENCIES: Department of Defense (DoD...: Final rule. SUMMARY: The Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council (Councils) have adopted as final, with changes, the interim rule amending the Federal Acquisition...

An innovative experimental sequence on electromagnetic induction and eddy currents based on video analysis and cheap data acquisition

International Nuclear Information System (INIS)

Bonanno, A; Sapia, P; Bozzo, G

2017-01-01

In this work, we present a coherent sequence of experiments on electromagnetic (EM) induction and eddy currents, appropriate for university undergraduate students, based on a magnet falling through a drilled aluminum disk. The sequence, leveraging on the didactical interplay between the EM and mechanical aspects of the experiments, allows us to exploit the students’ awareness of mechanics to elicit their comprehension of EM phenomena. The proposed experiments feature two kinds of measurements: (i) kinematic measurements (performed by means of high-speed video analysis) give information on the system’s kinematics and, via appropriate numerical data processing, allow us to get dynamic information, in particular on energy dissipation; (ii) induced electromagnetic field (EMF) measurements (by using a homemade multi-coil sensor connected to a cheap data acquisition system) allow us to quantitatively determine the inductive effects of the moving magnet on its neighborhood. The comparison between experimental results and the predictions from an appropriate theoretical model (of the dissipative coupling between the moving magnet and the conducting disk) offers many educational hints on relevant topics related to EM induction, such as Maxwell’s displacement current, magnetic field flux variation, and the conceptual link between induced EMF and induced currents. Moreover, the didactical activity gives students the opportunity to be trained in video analysis, data acquisition and numerical data processing. (paper)

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...

Defense Acquisition Workforce: The Air Force Needs to Evaluate Changes in Funding for Civilians Engaged in Space Acquisition

Science.gov (United States)

2013-07-01

1) revitalize the acquisition workforce; (2) improve the requirements generation process; (3) instill budget and financial DOD Acquisition...with our four recommended actions (see app . I). In concurring with our recommendations, DOD stated that the Air Force will evaluate the pilot program

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

Applying Rapid Acquisition Policy Lessons for Defense Innovation

Science.gov (United States)

2017-12-21

import- ing Silicon Valley- style innovation practices to its acquisition process, it is im- portant to assess an organization’s ability to...these efforts. Keywords: defense acquisition, defense procurement, rapid acquisition, de- fense innovation, program management , organizational culture...Device De- feat Organization, JIEDDO, Rapid Equipping Force, REF Silicon Valley- style innovation is a hot topic in the Department of De-fense (DOD). For

ROLE OF INTERNATIONAL MERGERS AND ACQUISITIONS IN CORPORATE INTEGRATION

OpenAIRE

Lucia P. BLĂJUȚ

2015-01-01

This paper highlights the role of international mergers and acquisitions in corporate integration. The factors that stimulate mergers and acquisitions activities bring real changes in the world economy. Mergers and acquisitions are a form of expansion: mergers can take place either as a statutory merger or consolidation and minority, majority or full acquisitions dominate the international market. It is very important to not confuse the meaning of the two terms. Multinational companies are fo...

VersaCold: Analysis of Change Management in Mergers & Acquisitions

OpenAIRE

Eslami, Sara

2011-01-01

Many firms use mergers and acquisitions as a corporate strategy to increase shareholder value. Therefore, understanding such a widely exercised strategy and its implications on corporate change would be critical for organizations that wish to pursue this strategy. This study provides an in depth review of mergers and acquisitions and introduces best practices for managing changes that result from mergers and acquisitions. Next, the concepts are applied to two cases of acquisitions in VersaCol...

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

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…

High temporal resolution magnetic resonance imaging: development of a parallel three dimensional acquisition method for functional neuroimaging

International Nuclear Information System (INIS)

Rabrait, C.

2007-11-01

Echo Planar Imaging is widely used to perform data acquisition in functional neuroimaging. This sequence allows the acquisition of a set of about 30 slices, covering the whole brain, at a spatial resolution ranging from 2 to 4 mm, and a temporal resolution ranging from 1 to 2 s. It is thus well adapted to the mapping of activated brain areas but does not allow precise study of the brain dynamics. Moreover, temporal interpolation is needed in order to correct for inter-slices delays and 2-dimensional acquisition is subject to vascular in flow artifacts. To improve the estimation of the hemodynamic response functions associated with activation, this thesis aimed at developing a 3-dimensional high temporal resolution acquisition method. To do so, Echo Volume Imaging was combined with reduced field-of-view acquisition and parallel imaging. Indeed, E.V.I. allows the acquisition of a whole volume in Fourier space following a single excitation, but it requires very long echo trains. Parallel imaging and field-of-view reduction are used to reduce the echo train durations by a factor of 4, which allows the acquisition of a 3-dimensional brain volume with limited susceptibility-induced distortions and signal losses, in 200 ms. All imaging parameters have been optimized in order to reduce echo train durations and to maximize S.N.R., so that cerebral activation can be detected with a high level of confidence. Robust detection of brain activation was demonstrated with both visual and auditory paradigms. High temporal resolution hemodynamic response functions could be estimated through selective averaging of the response to the different trials of the stimulation. To further improve S.N.R., the matrix inversions required in parallel reconstruction were regularized, and the impact of the level of regularization on activation detection was investigated. Eventually, potential applications of parallel E.V.I. such as the study of non-stationary effects in the B.O.L.D. response

Control and data acquisition system for Beam Line C and HRS

International Nuclear Information System (INIS)

Naivar, F.J.; Rogers, W.L.; Simmonds, D.D.; Spencer, J.E.; Spencer, N.C.; Stark, C.F.

1977-03-01

The High Resolution Spectrometer (HRS) at LAMPF is a multimillion dollar facility intended for the study of proton induced reactions and scattering with 100 to 800 MeV protons. It will be used by research scientists from universities and other national laboratories throughout the United States. The design resolution of +-1.5:10 -5 is better than any similar system ever attempted in this energy range. To obtain this quality as well as fully realize the research potential of the facility, a rather sophisticated computer control and data acquisition system is required. The facility, based on a general multiuser, multitask, multiprocessor system, is described

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.

VME data acquisition system. Interactive software for the acquisition, display and storage of one or two dimensional spectra

International Nuclear Information System (INIS)

Petremann, E.

1989-01-01

The development and construction of a complete data acquisition system for nuclear physics applications, are described. The system is based on the VME bus and the 16/32 bits microprocessor. The data acquisition system enables the obtention of line spectra, involving one or two parameters, and the simultaneous storage of events in a magnetic tape. The analysis and the description of the data acquisition software, the experimental spectra display and saving on magnetic systems are given. Pascal and Assembler are used. The development of cards, for the standard VME and electronic equipment interfaces, is performed [fr

48 CFR 939.7002 - Contractor acquisition of information technology.

Science.gov (United States)

2010-10-01

... information technology. 939.7002 Section 939.7002 Federal Acquisition Regulations System DEPARTMENT OF ENERGY SPECIAL CATEGORIES OF CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY Implementing DOE Policies and Procedures 939.7002 Contractor acquisition of information technology. (a) Management and operating (M&O...

Handgun Acquisitions in California After Two Mass Shootings.

Science.gov (United States)

Studdert, David M; Zhang, Yifan; Rodden, Jonathan A; Hyndman, Rob J; Wintemute, Garen J

2017-05-16

Mass shootings are common in the United States. They are the most visible form of firearm violence. Their effect on personal decisions to purchase firearms is not well-understood. To determine changes in handgun acquisition patterns after the mass shootings in Newtown, Connecticut, in 2012 and San Bernardino, California, in 2015. Time-series analysis using seasonal autoregressive integrated moving-average (SARIMA) models. California. Adults who acquired handguns between 2007 and 2016. Excess handgun acquisitions (defined as the difference between actual and expected acquisitions) in the 6-week and 12-week periods after each shooting, overall and within subgroups of acquirers. In the 6 weeks after the Newtown and San Bernardino shootings, there were 25 705 (95% prediction interval, 17 411 to 32 788) and 27 413 (prediction interval, 15 188 to 37 734) excess acquisitions, respectively, representing increases of 53% (95% CI, 30% to 80%) and 41% (CI, 19% to 68%) over expected volume. Large increases in acquisitions occurred among white and Hispanic persons, but not among black persons, and among persons with no record of having previously acquired a handgun. After the San Bernardino shootings, acquisition rates increased by 85% among residents of that city and adjacent neighborhoods, compared with 35% elsewhere in California. The data relate to handguns in 1 state. The statistical analysis cannot establish causality. Large increases in handgun acquisitions occurred after these 2 mass shootings. The spikes were short-lived and accounted for less than 10% of annual handgun acquisitions statewide. Further research should examine whether repeated shocks of this kind lead to substantial increases in the prevalence of firearm ownership. None.

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...

AZ-101 Mixer Pump Demonstration Data Acquisition System and Gamma Cart Data Acquisition Control System Software Configuration Management Plan

International Nuclear Information System (INIS)

WHITE, D.A.

1999-01-01

This Software Configuration Management Plan (SCMP) provides the instructions for change control of the AZ1101 Mixer Pump Demonstration Data Acquisition System (DAS) and the Sludge Mobilization Cart (Gamma Cart) Data Acquisition and Control System (DACS)

Cross-linguistic patterns in the acquisition of quantifiers

Science.gov (United States)

Cummins, Chris; Gavarró, Anna; Kuvač Kraljević, Jelena; Hrzica, Gordana; Grohmann, Kleanthes K.; Skordi, Athina; Jensen de López, Kristine; Sundahl, Lone; van Hout, Angeliek; Hollebrandse, Bart; Overweg, Jessica; Faber, Myrthe; van Koert, Margreet; Smith, Nafsika; Vija, Maigi; Zupping, Sirli; Kunnari, Sari; Morisseau, Tiffany; Rusieshvili, Manana; Yatsushiro, Kazuko; Fengler, Anja; Varlokosta, Spyridoula; Konstantzou, Katerina; Farby, Shira; Guasti, Maria Teresa; Vernice, Mirta; Okabe, Reiko; Isobe, Miwa; Crosthwaite, Peter; Hong, Yoonjee; Balčiūnienė, Ingrida; Ahmad Nizar, Yanti Marina; Grech, Helen; Gatt, Daniela; Cheong, Win Nee; Asbjørnsen, Arve; Torkildsen, Janne von Koss; Haman, Ewa; Miękisz, Aneta; Gagarina, Natalia; Puzanova, Julia; Anđelković, Darinka; Savić, Maja; Jošić, Smiljana; Slančová, Daniela; Kapalková, Svetlana; Barberán, Tania; Özge, Duygu; Hassan, Saima; Chan, Cecilia Yuet Hung; Okubo, Tomoya; van der Lely, Heather; Sauerland, Uli; Noveck, Ira

2016-01-01

Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier’s specific meaning. We investigate competence with the expressions for “all,” “none,” “some,” “some…not,” and “most” in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language- and learner-specific factors, such as negative concord and gender, are significant predictors of variation. PMID:27482119

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

Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75

Directory of Open Access Journals (Sweden)

Leoh Lai

2009-08-01

Full Text Available Abstract Background Hormone-refractory prostate cancer (HRPC is characterized by poor response to chemotherapy and high mortality, particularly among African American men when compared to other racial/ethnic groups. It is generally accepted that docetaxel, the standard of care for chemotherapy of HRPC, primarily exerts tumor cell death by inducing mitotic catastrophe and caspase-dependent apoptosis following inhibition of microtubule depolymerization. However, there is a gap in our knowledge of mechanistic events underlying docetaxel-induced caspase-independent cell death, and the genes that antagonize this process. This knowledge is important for circumventing HRPC chemoresistance and reducing disparities in prostate cancer mortality. Results We investigated mechanistic events associated with docetaxel-induced death in HRPC cell lines using various approaches that distinguish caspase-dependent from caspase-independent cell death. Docetaxel induced both mitotic catastrophe and caspase-dependent apoptosis at various concentrations. However, caspase activity was not essential for docetaxel-induced cytotoxicity since cell death associated with lysosomal membrane permeabilization still occurred in the presence of caspase inhibitors. Partial inhibition of docetaxel-induced cytotoxicity was observed after inhibition of cathepsin B, but not inhibition of cathepsins D and L, suggesting that docetaxel induces caspase-independent, lysosomal cell death. Simultaneous inhibition of caspases and cathepsin B dramatically reduced docetaxel-induced cell death. Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75, a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal destabilization and cell death. Interestingly, LEDGF/p75 overexpression did not protect cells against DTX-induced mitotic catastrophe, and against apoptosis induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL

Foreign acquisitions, domestic multinationals, and R&D

DEFF Research Database (Denmark)

Bandick, Roger; Görg, Holger; Karpaty, Patrik

2014-01-01

The aim of this paper is to evaluate the causal effect of foreign acquisition on R&D intensity in targeted domestic firms. We are able to distinguish domestic multinationals and non-multinationals, which allows us to investigate the fear that the change in ownership of domestic to foreign...... multinationals leads to a reduction in R&D activity in the country. We use unique and rich firm level data for the Swedish manufacturing sector and micro-econometric estimation strategies in order to control for the potential endogeneity of the acquisition decision. Overall, our results give no support...... to the fears that foreign acquisition of domestic firms lead to a relocation of R&D activity in Swedish MNEs. Rather, this paper finds robust evidence that foreign acquisitions lead to increasing R&D intensity in acquired domestic MNEs and non-MNEs....

Disentangling value creation mechanism in cross-border acquisitions

DEFF Research Database (Denmark)

Wang, Daojuan; Sørensen, Olav Jull; Moini, Hamid

2016-01-01

This study investigates the value creation mechanism in cross-border acquisitions ( CBAs ) by employing a structural equation modeling technique and surveying 103 CBAs performed by Nordic firms. The results reveal that resource possession, resource picking, and resource utilization are three impo...... in this study, is an important step forward in merger and acquisition (M&A) research. Moreover, numerous research findings offer tactical implications for international acquirers.......This study investigates the value creation mechanism in cross-border acquisitions ( CBAs ) by employing a structural equation modeling technique and surveying 103 CBAs performed by Nordic firms. The results reveal that resource possession, resource picking, and resource utilization are three...... important strategic dimensions for realizing synergy and creating value in CBAs . Furthermore, mediation analysis shows that the two acquisition-based dynamic capabilities—value identification and resource reconfiguration—act as important mediators in how the joining firms’ resource base impacts acquisition...

Book Review : A DICTIONARY OF LANGUAGE ACQUISITION: A COMPREHENSIVE OVERVIEW OF KEY TERMS IN FIRST AND SECOND LANGUAGE ACQUISITION

OpenAIRE

Kaswan Kaswan

2014-01-01

As  with language, language acquisition (LA), particularly second language acquisition (SLA)  is not simple. SLA  is complex  and paradoxical.  SLA is complex because it cannot be scrutinized using a single approach.  SLA  is complex;  nevertheless  it is  a curious fact that the study of  (SLA has historically been dominated by a single broad approach—that which goes by the name of “cognitive (Atkinson (ed), 2011). Among views on acquisition which can be characterized as cognitive are: 1...

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

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

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)

Acquisition of Scientific Literature in Developing Countries. 2: Malaysia.

Science.gov (United States)

Taib, Rosna

1989-01-01

Describes the acquisition of scientific literature by academic libraries in Malaysia. The discussion covers the impact of government policies, library acquisition policies, the selection process, acquisition of special materials, the role of gifts and exchanges, and problems with customs clearance and censorship. Progress in cooperative…

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

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

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

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…

How Cisco Systems Used Enterprise Architecture Capability to Sustain Acquisition-Based Growth

DEFF Research Database (Denmark)

Toppenberg, Gustav; Shanks, Graeme; Henningsson, Stefan

2015-01-01

Value-creating acquisitions are a major challenge for many firms. The case of Cisco Systems shows that an advanced enterprise architecture (EA) capability can contribute to the four phases of the acquisition process: pre-acquisition preparation, acquisition selection, acquisition integration...... and post-integration management. Cisco’s EA capability improves its ability to rapidly capture value from acquisitions and to sustain its acquisition-based growth strategy over time....

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

LENUS (Irish Health Repository)

d'Adhemar, Charles J

2014-01-01

pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

Directory of Open Access Journals (Sweden)

Charles J d'Adhemar

/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

Study of customer acquisition support system for mobile operators

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

The mobile operators are struggling for improving the market share and the revenues.One important method is to acquire the potential customers from the competitors.This article presents a whole acquisition process and an integrated framework for customer acquisition support system (CASS).The core of the system is the customer acquisition identification models which are built based on data mining technologies.The CASS can automate the acquisition process and decrease the cost and implement precise marketing strategy for mobile operators.

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

The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

Science.gov (United States)

Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2018-05-16

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

48 CFR 227.7103-2 - Acquisition of technical data.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Acquisition of technical... Rights in Technical Data 227.7103-2 Acquisition of technical data. (a) Contracting officers shall work... personnel are responsible for identifying the Government's minimum needs for technical data. Data needs must...

48 CFR 307.7001 - Distinction between acquisition and assistance.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Distinction between acquisition and assistance. 307.7001 Section 307.7001 Federal Acquisition Regulations System HEALTH AND HUMAN... barter, of property or services for the direct benefit or use of the Government; or (2) Government...

Attenuation of everolimus-induced cytotoxicity by a protective autophagic pathway involving ERK activation in renal cell carcinoma cells

Science.gov (United States)

Zeng, Yizhou; Tian, Xiaofang; Wang, Quan; He, Weiyang; Fan, Jing; Gou, Xin

2018-01-01

Aim The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway. Methods and results: RAD001 strongly induced autophagy of RCC cells in a dose- and time-dependent manner, as confirmed by Western blot analysis. Importantly, suppression of autophagy by the pharmacological inhibitor chloroquine effectively enhanced RAD001-induced apoptotic cytotoxicity, as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, indicating a cytoprotective role for RAD001-induced autophagy. In addition, as was shown by the MTT assay, flow cytometry, and Western blot analysis, RAD001 robustly activated ERK, but not c-Jun N-terminal kinase and p38. Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. Moreover, employing AZD6244 markedly attenuated RAD001-induced autophagy and enhanced RAD001-induced apoptosis, which play a central role in RAD001-induced cell death. Furthermore, RAD001-induced autophagy is regulated by ERK-mediated phosphorylation of Beclin-1 and B-cell lymphoma 2, as confirmed by Western blot analysis. Conclusion These results suggest that RAD001-induced autophagy involves activation of the ERK, which may impair cytotoxicity of RAD001 in RCC cells. Thus, inhibition of the activation of ERK pathway-mediated autophagy may be useful to overcome chemoresistance to RAD001. PMID:29719377

High temporal resolution magnetic resonance imaging: development of a parallel three dimensional acquisition method for functional neuroimaging; Imagerie par resonance magnetique a haute resolution temporelle: developpement d'une methode d'acquisition parallele tridimensionnelle pour l'imagerie fonctionnelle cerebrale

Energy Technology Data Exchange (ETDEWEB)

Rabrait, C

2007-11-15

Echo Planar Imaging is widely used to perform data acquisition in functional neuroimaging. This sequence allows the acquisition of a set of about 30 slices, covering the whole brain, at a spatial resolution ranging from 2 to 4 mm, and a temporal resolution ranging from 1 to 2 s. It is thus well adapted to the mapping of activated brain areas but does not allow precise study of the brain dynamics. Moreover, temporal interpolation is needed in order to correct for inter-slices delays and 2-dimensional acquisition is subject to vascular in flow artifacts. To improve the estimation of the hemodynamic response functions associated with activation, this thesis aimed at developing a 3-dimensional high temporal resolution acquisition method. To do so, Echo Volume Imaging was combined with reduced field-of-view acquisition and parallel imaging. Indeed, E.V.I. allows the acquisition of a whole volume in Fourier space following a single excitation, but it requires very long echo trains. Parallel imaging and field-of-view reduction are used to reduce the echo train durations by a factor of 4, which allows the acquisition of a 3-dimensional brain volume with limited susceptibility-induced distortions and signal losses, in 200 ms. All imaging parameters have been optimized in order to reduce echo train durations and to maximize S.N.R., so that cerebral activation can be detected with a high level of confidence. Robust detection of brain activation was demonstrated with both visual and auditory paradigms. High temporal resolution hemodynamic response functions could be estimated through selective averaging of the response to the different trials of the stimulation. To further improve S.N.R., the matrix inversions required in parallel reconstruction were regularized, and the impact of the level of regularization on activation detection was investigated. Eventually, potential applications of parallel E.V.I. such as the study of non-stationary effects in the B.O.L.D. response

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

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....

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.

Aesthetic chills: Knowledge-acquisition, meaning-making and aesthetic emotions

Directory of Open Access Journals (Sweden)

Leonid Perlovsky

2016-08-01

Full Text Available This article addresses the relation between aesthetic emotions, knowledge-acquisition, and meaning-making. We briefly review theoretical foundations and present experimental data related to aesthetic chills. These results suggest that aesthetic chills are inhibited by exposing the subject to an incoherent prime prior to the chill-eliciting stimulation, and that a meaningful prime makes the aesthetic experience more pleasurable than a neutral or an incoherent one. Aesthetic chills induced by narrative structures seem to be related to the pinnacle of the story, to have a significant calming effect and subjects describe a strong empathy for the characters. We discuss the relation between meaning-making and aesthetic emotions at the psychological, physiological, narratological, and mathematical levels and propose a series of hypotheses to be tested in future research.

7 CFR 1735.62 - Approval of acquisitions and mergers.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Approval of acquisitions and mergers. 1735.62 Section 1735.62 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE... Mortgage Controls on Acquisitions and Mergers § 1735.62 Approval of acquisitions and mergers. (a) If a...

30 CFR 879.12 - Procedures for acquisition.

Science.gov (United States)

2010-07-01

....12 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.12... adversely affected by past mining. (b) When practical, acquisition shall be by purchase from a willing...

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

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.

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

Directory of Open Access Journals (Sweden)

Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

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

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

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.

Human Robotic Systems (HRS): Robotic ISRU Acquisition Element

Data.gov (United States)

National Aeronautics and Space Administration — During 2014, the Robotic ISRU Resource Acquisition project element will develop two technologies:Exploration Ground Data Systems (xGDS)Sample Acquisition on...

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

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...

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

Right-Sizing the Department of Defense Acquisition Workforce

National Research Council Canada - National Science Library

1997-01-01

.... Through the leadership of vigorous acquisition reform, astute management in a highly dynamic environment and great innovation, the acquisition workforce will be significantly smaller at the end of FY...

7 CFR 982.16 - Inshell trade acquisitions.

Science.gov (United States)

2010-01-01

... acquisitions means the quantity of inshell hazelnuts acquired by the trade from all handlers during a marketing... 7 Agriculture 8 2010-01-01 2010-01-01 false Inshell trade acquisitions. 982.16 Section 982.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing...

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

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.

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

Reference-free unwarping of single-shot spatiotemporally encoded MRI using asymmetric self-refocused echoes acquisition

Science.gov (United States)

Chen, Ying; Chen, Song; Zhong, Jianhui; Chen, Zhong

2015-05-01

This paper presents a phase evolution rewinding algorithm for correcting the geometric and intensity distortions in single-shot spatiotemporally encoded (SPEN) MRI with acquisition of asymmetric self-refocused echo trains. Using the field map calculated from the phase distribution of the source image, the off-resonance induced phase errors are successfully rewound through deconvolution. The alias-free partial Fourier transform reconstruction helps improve the signal-to-noise ratio of the field maps and the output images. The effectiveness of the proposed algorithm was validated through 7 T MRI experiments on a lemon, a water phantom, and in vivo rat head. SPEN imaging was evaluated using rapid acquisition by sequential excitation and refocusing (RASER) which produces uniform T2 weighting. The results indicate that the new technique can more robustly deal with the cases in which the images obtained with conventional single-shot spin-echo EPI are difficult to be restored due to serious field variations.

Electromagnetic Compatibility Assessment of CCD Detector Acquisition Chains not Synchronized

Science.gov (United States)

Nicoletto, M.; Boschetti, D.; Ciancetta, E.; Maiorano, E.; Stagnaro, L.

2016-05-01

Euclid is a space observatory managed by the European Space Agency; it is the second medium class mission (see Figure 1) in the frame of Cosmic Vision 2015-2025 program.In the frame of this project, the electromagnetic interference between two different and not synchronized Charge Coupled Device (CCD) (see Figure 2) acquisition chains has been evaluated. The key parameter used for this assessment is the electromagnetic noise induced on each other. Taking into account the specificity of the issue, radiation coupling at relative low frequency and in near field conditions, classical approach based on simulations and testing on qualification model cannot be directly applied. Based on that, it has been decided to investigate the issue by test in an incremental way.

Data acquisition for X ray microprobe. User's manual

International Nuclear Information System (INIS)

2002-01-01

A modified data acquisition software for X ray microprobe was developed by the Physics Group, Instrumentation Unit, IAEA Laboratories at Seibersdorf, with assistance from M. Bogovac, Croatia. The software consists of data acquisition (scanning and calibration), automatic positioning and micro-movement of sample, data reduction and evaluation. The acquisition software was designed in order to support different measurement set-ups which are applied in low-energy nuclear physics. The modification was done in 1999-2000 under the projects Nuclear Spectrometry and Utilization of Particle Accelerators. The manual supersedes the first version entitled Microanalysis Data Acquisition and Control Program published under Computer Manual Series, No. 9 in 1996. The software described in this manual is freely available from the IAEA upon request

Air Traffic Control: Immature Software Acquisition Processes Increase FAA System Acquisition Risks

Science.gov (United States)

1997-03-01

The General Accounting Office (GAO) at the request of Congress reviewed (1) : the maturity of Federal Aviation Administration's (FAA's) Air Traffic Control : (ATC) modernization software acquisition processes, and (2) the steps/actions : FAA has unde...

Comparison of continuous with step and shoot acquisition in SPECT scanning

International Nuclear Information System (INIS)

McCarthy, L.; Cotterill, T.; Chu, J.M.G.

1998-01-01

Full text: Following the recent advent of continuous acquisition for performing SPECT scanning, it was decided to compare the commonly used Step and Shoot mode of acquisition with the new continuous acquisition mode. The aim of the study is to assess any difference in resolution from the resulting images acquired using the two modes of acquisition. Sequential series of studies were performed on a SPECT phantom using both modes of acquisition. Separate sets of data were collected for both high resolution parallel hole and ultra high resolution fan beam collimators. Clinical data was collected on patients undergoing routine gallium, 99m Tc-MDP bone and 99m Tc-HMPAO brain studies. Separate sequential acquisition in both modes were collected for each patient. The sequence of collection was also alternated. Reconstruction was performed utilising the same parameters for each acquisition. The reconstructed data were assessed visually by blinded observers to detect differences in resolution and image quality. No significant difference in the studies collected by either acquisition modes were detected. The time saved by continuous acquisition could be an advantage

Impact of acquisition channels on customer equity, The

OpenAIRE

Villanueva, Julian; Yoo, Shijin; Hanssens, Dominique M.

2003-01-01

Customer equity (CE henceforth) is a powerful new paradigm to evaluate the firm's value and to optimally allocate marketing resources. This paper is focused on the relationship between customer acquisition and CE. The authors attempt to answer the following four questions: 1) how should customer acquisition channels be categorized to make them meaningful to managers and academics?; 2) how do we measure the effects of different acquisition channels on the firm's performance?; 3) how do we dise...

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)

Acquisition Review Quarterly (ARQ) Vol. 4, No. 4

National Research Council Canada - National Science Library

1997-01-01

The primary goal of the Acquisition Review quarterly (ARQ) is to provide practicing acquisition professionals with relevant management tools and information based on recent advances in policy, management theory, and research...

A Framework for Operational Due Diligence in Mergers and Acquisitions

DEFF Research Database (Denmark)

Porsgaard, Chris Berg; Haubjerg, Mathias; Herbert-Hansen, Zaza Nadja Lee

The number of mergers and acquisitions (M&As) has over the last five years increased greatly (Institute of Mergers, Acquisitions and Alliances, 2016). Furthermore, private equity professionals point to operational performance gains to drive an acquisition decision and attribute cost reductions...... as the most important lever for value creation, after a private equity firm acquires a company (PwC, 2016). However, the overall success rate of M&A activity remains low and the approach to understand an acquisition target’s operating model remains non-exhaustive and unstandardized. This paper investigates...... the pivotal eterminants for assessing operational performance and identifying improvement potentials in an acquisition target. The research question is: “What are the fundamental operational determinants influencing the acquisition decision for private equity firms in the due diligence phase?” This paper...

78 FR 53761 - Federal Acquisition Regulation; Submission for OMB Review; Commercial Item Acquisitions

Science.gov (United States)

2013-08-30

... provided. FOR FURTHER INFORMATION CONTACT: Mr. Michael O. Jackson, Procurement Analyst, Office of Governmentwide Acquisition Policy, GSA (202) 208- 4949 or email at michaelo.jackson@gsa.gov . SUPPLEMENTARY...

Impact of Merger and Acquisition on University Performance.

Science.gov (United States)

Mohamadi Bolbanabad, Amjad; Mosadeghrad, Ali Mohammad; Arab, Mohammad; Majdzadeh, Reza

2017-08-01

Merger and acquisitions (M&A) widen access to higher education, improve quality of teaching and research, and increase efficiency of higher education institutions. Three big medical universities in Iran merged in 2010. The purpose of this study was to highlight the impact of this acquisition on the performance of Tehran University of Medical Sciences. This qualitative study was conducted using semi-structured in-depth interviews with 60 participants from April 2015 to November 2015. Purposeful sampling was used to recruit participants. Data analysis was performed using MAXQDA software (V. 10). The reasons for acquisition of IUMS by TUMS were to enhance the position of TUMS worldwide, and to increase its efficiency. The acquisition improved the organization and management of the newly formed TUMS, enhanced its academic position and market recognition. However, the achieved benefits did not come without shortcomings and unanticipated consequences. The merger and acquisition in higher education has some advantages and disadvantages. A well planned and carefully implemented M&A gives cutting edge to the higher education institutes.

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)

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...

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

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

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.

Language acquisition is model-based rather than model-free.

Science.gov (United States)

Wang, Felix Hao; Mintz, Toben H

2016-01-01

Christiansen & Chater (C&C) propose that learning language is learning to process language. However, we believe that the general-purpose prediction mechanism they propose is insufficient to account for many phenomena in language acquisition. We argue from theoretical considerations and empirical evidence that many acquisition tasks are model-based, and that different acquisition tasks require different, specialized models.

A data acquisition system based on a personal computer

International Nuclear Information System (INIS)

Omata, K.; Fujita, Y.; Yoshikawa, N.; Sekiguchi, M.; Shida, Y.

1991-07-01

A versatile and flexible data acquisition system KODAQ (Kakuken Online Data AcQuisition system) has been developed. The system runs with CAMAC and a most popular Japanese personal computer, PC9801 (NEC), similar to the IBM PC/AT. The system is designed to set up easily a data acquisition system for various kinds of nuclear-physics experiments. (author)

Hardware and software for image acquisition in nuclear medicine

International Nuclear Information System (INIS)

Fideles, E.L.; Vilar, G.; Silva, H.S.

1992-01-01

A system for image acquisition and processing in nuclear medicine is presented, including the hardware and software referring to acquisition. The hardware is consisted of an analog-digital conversion card, developed in wire-wape. Its function is digitate the analogic signs provided by gamma camera. The acquisitions are made in list or frame mode. (C.G.C.)

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...

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

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...

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...

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....

On Cultivating Students' Motivation in Second Language Acquisition

Institute of Scientific and Technical Information of China (English)

沈小平

2009-01-01

This paper attempts to explore the cultivation of motivation in second language acquisition based on shedding new light on the definition, the importance, and the classification of learners' motivation in second language acquisition.

Single-Shot, Volumetrically Illuminated, Three-Dimensional, Tomographic Laser-Induced-Fluorescence Imaging in a Gaseous Free Jet

Science.gov (United States)

2016-04-28

Single-shot, volumetrically illuminated, three- dimensional, tomographic laser-induced- fluorescence imaging in a gaseous free jet Benjamin R. Halls...acquisition; (110.6955) Tomographic imaging ; (110.6960) Tomography; (280.2490) Flow diagnostics; (300.2530) Fluorescence , laser-induced...84 (1983). 2. I. van Cruyningen, A. Lozano, and R. K. Hanson, “Quantitative imaging of concentration by planar laser-induced fluorescence ,” Exp

48 CFR 18.106 - Acquisitions from Federal Prison Industries, Inc. (FPI).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Acquisitions from Federal Prison Industries, Inc. (FPI). 18.106 Section 18.106 Federal Acquisition Regulations System FEDERAL... Flexibilities 18.106 Acquisitions from Federal Prison Industries, Inc. (FPI). Purchase from FPI is not mandatory...

Design of data acquisition system for GEM detector

International Nuclear Information System (INIS)

Lu Jianliang; Chen Ziyu; Shen Ji; Jin Xi

2011-01-01

It describes the design and realization of the USB 2.0 high speed data acquisition devise which is used in the readout electronics of the GEM (gas electron multiplier) detector. By using of the USB Microcontroller EZ-USB FX2 CY7C68013A, high speed ADC and FPGA, high-speed data rate of data acquisition and transmission was realized. The data rate reaches to 20 MByte/s, meeting the requirements of data acquisition and transmission of the detector. (authors)

Strategy and Tactics of International Mergers and Acquisitions

Directory of Open Access Journals (Sweden)

Denys Kiriakov

2011-12-01

Full Text Available The article reviews contemporary strategy and tactics issues in terms of international mergers and acquisitions, along with displaying cyclical waves of mergers and acquisitions over the last century as well as motivation thereof. Five strategies adhered to by international companies initiating conclusion of such agreements as well as challenges accompanying execution thereof have been analyzed. Modern strategic and tactical tools of international mergers and acquisitions process management have been researched on exemplary buyer (a corporation case-study.

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)

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)

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.

Improvement of Sidestream Dark Field Imaging with an Image Acquisition Stabilizer

International Nuclear Information System (INIS)

Balestra, Gianmarco M; Bezemer, Rick; Boerma, E Christiaan; Yong, Ze-Yie; Sjauw, Krishan D; Engstrom, Annemarie E; Koopmans, Matty; Ince, Can

2010-01-01

In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging. The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared. Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 ± 0.15 N without vs. 0.62 ± 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 ± 2 s without vs. 42 ± 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 ± 5 s without vs. 67 ± 14 s with the IAS, p = 0.006). The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS

Acquisition with partial and continuous reinforcement in pigeon autoshaping.

Science.gov (United States)

Gottlieb, Daniel A

2004-08-01

Contemporary time accumulation models make the unique prediction that acquisition of a conditioned response will be equally rapid with partial and continuous reinforcement, if the time between conditioned stimuli is held constant. To investigate this, acquisition of conditioned responding was examined in pigeon autoshaping under conditions of 100% and 25% reinforcement, holding intertrial interval constant. Contrary to what was predicted, evidence for slowed acquisition in partially reinforced animals was observed with several response measures. However, asymptotic performance was superior with 25% reinforcement. A switching of reinforcement contingencies after initial acquisition did not immediately affect responding. After further sessions, partial reinforcement augmented responding, whereas continuous reinforcement did not, irrespective of an animal's reinforcement history. Subsequent training with a novel stimulus maintained the response patterns. These acquisition results generally support associative, rather than time accumulation, accounts of conditioning.

Turkish Air Force's Experiences in Chemical Material Acquisition

National Research Council Canada - National Science Library

Taskiran, Huseyin

2002-01-01

.... In addition, it analyzes the chemical material acquisition from business perspective. Due to operating in different environments, the Turkish Air Force and the private sector have different objectives in the acquisition of chemical materials...

48 CFR 2953.102 - Quotation for Simplified Acquisitions DL 1-2078.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Quotation for Simplified Acquisitions DL 1-2078. 2953.102 Section 2953.102 Federal Acquisition Regulations System DEPARTMENT OF LABOR CLAUSE AND FORMS FORMS General 2953.102 Quotation for Simplified Acquisitions DL 1-2078. The following...

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...

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...

Multi-channel data acquisition system for CT

International Nuclear Information System (INIS)

Cao Fuqiang; He Bin; Liu Guohua; Xu Minjian

2009-01-01

The architecture design and realization of a data acquisition system for multi-channel CT is described. The article introduces the conversion of analog signal to digital signal, the data cache and transmission. This data acquisition system can be widely used in the system which requires the multi-channel, weak current signal detection. (authors)

Knowledge Acquisition Using Linguistic-Based Knowledge Analysis

Science.gov (United States)

Daniel L. Schmoldt

1998-01-01

Most knowledge-based system developmentefforts include acquiring knowledge from one or more sources. difficulties associated with this knowledge acquisition task are readily acknowledged by most researchers. While a variety of knowledge acquisition methods have been reported, little has been done to organize those different methods and to suggest how to apply them...

Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

Directory of Open Access Journals (Sweden)

Yu-Chun Wang

2013-11-01

Full Text Available Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME. Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv significantly decreased blood pressure of rabbits and NA or DTC injection (iv did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO, but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports

Science.gov (United States)

2017-12-01

by the Army Acquisition Executive contains the following language . As a recently delegated Acquisition Category IC program, the AH-64E Apache...Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports Gregory A. Davis, Project Leader Margaret L. Giles David M. Tate I...F E N S E A N A L Y S E S IDA Paper P-8490 Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports Gregory A. Davis

SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell.

Science.gov (United States)

Feng, Chenzhe; Ma, Fang; Hu, Chunhong; Ma, Jin-An; Wang, Jingjing; Zhang, Yang; Wu, Fang; Hou, Tao; Jiang, Shun; Wang, Yapeng; Feng, Yeqian

2018-01-01

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

War-gaming application for future space systems acquisition part 2: acquisition and bidding war-gaming modeling and simulation approaches for FFP and FPIF

Science.gov (United States)

Nguyen, Tien M.; Guillen, Andy T.

2017-05-01

This paper describes cooperative and non-cooperative static Bayesian game models with complete and incomplete information for the development of optimum acquisition strategies associated with the Program and Technical Baseline (PTB) solutions obtained from Part 1 of this paper [1]. The optimum acquisition strategies discussed focus on achieving "Affordability" by incorporating contractors' bidding strategies into the government acquisition strategies for acquiring future space systems. The paper discusses System Engineering (SE) frameworks, analytical and simulation approaches and modeling for developing the optimum acquisition strategies from both the government and contractor perspectives for Firm Fixed Price (FFP) and Fixed Price Incentive Firm (FPIF) contract types.

48 CFR 7.107 - Additional requirements for acquisitions involving bundling.

Science.gov (United States)

2010-10-01

...; and (2) The acquisition strategy provides for maximum practicable participation by small business... the Government. However, because of the potential impact on small business participation, the head of... acquisition strategy involves substantial bundling, the acquisition strategy must additionally— (1) Identify...

76 FR 13297 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Science.gov (United States)

2011-03-11

... 215 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations System... Director, Defense Procurement and Acquisition Policy. DATES: Effective Date: March 11, 2011. Applicability... adding a section at 215.300 with a reference to Director, Defense Procurement and Acquisition Policy...

Shortening the Defense Acquisition Cycle: A Transformational Imperative?

National Research Council Canada - National Science Library

Vollmecke, Kirk

2004-01-01

.... The acquisition system is both political and complex. This Strategy Research Project paper explores the effectiveness of past policy changes to reduce cycle time, and reviews current acquisition issues or problems related to cycle time reduction...

The image acquisition system design of floor grinder

Science.gov (United States)

Wang, Yang-jiang; Liu, Wei; Liu, Hui-qin

2018-01-01

Based on linear CCD, high resolution image real-time acquisition system serves as designing a set of image acquisition system for floor grinder through the calculation of optical imaging system. The entire image acquisition system can collect images of ground before and after the work of the floor grinder, and the data is transmitted through the Bluetooth system to the computer and compared to realize real-time monitoring of its working condition. The system provides technical support for the design of unmanned ground grinders.

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

128 Channel PCI-based data acquisition system for MDSplus

Energy Technology Data Exchange (ETDEWEB)

Llobet, Xavier E-mail: xavier.llobet@epfl.ch; Duval, Basil P. E-mail: basil.duval@epfl.ch

2002-06-01

With the increasing demand for analogue channel acquisition on the TCV tokamak, a new PCI based acquisition has been specified, designed, built and installed into our MDSplus acquisition environment. The design criteria were to not only improve the cost/channel, as compared to our conventional hub based acquisition (CAMAC), but to provide some distributed processing power to avoid the associated acquisition server saturation, both in terms of CPU and network bandwidth. These units were initially intended to satisfy the requirements of general variable rate acquisition from a variety of sources, and many channel acquisition from modern multi-channel diagnostics. Hosted by a i386-Linux PC in a crate with four available PCI slots, each single-PCI slot 32-channel digitiser features sampling frequencies up to 200 kHz, and 64 MB of memory, providing 1 Msample of 16-bit data per channel. The local hard disk is used for immediate local storage of all the acquired data from the selected channels into a local MDSplus database. The host is then accessed as a MDS/IP server that provides, on demand, down-sampled and software filtered traces. The local hard disk capacity is used for medium to long-term storage and availability of the full data set with optional mirror technology to guard against hard disk failure. We have thus obtained a general solution for high resolution, multi-channel routine acquisition using the multi-platform MDSplus environment, in which different software and hardware architectures are intelligently linked across a standard TCP/IP network. The implementation presented here uses ONLY standard components of the MDSplus environment.

128 Channel PCI-based data acquisition system for MDSplus

International Nuclear Information System (INIS)

Llobet, Xavier; Duval, Basil P.

2002-01-01

With the increasing demand for analogue channel acquisition on the TCV tokamak, a new PCI based acquisition has been specified, designed, built and installed into our MDSplus acquisition environment. The design criteria were to not only improve the cost/channel, as compared to our conventional hub based acquisition (CAMAC), but to provide some distributed processing power to avoid the associated acquisition server saturation, both in terms of CPU and network bandwidth. These units were initially intended to satisfy the requirements of general variable rate acquisition from a variety of sources, and many channel acquisition from modern multi-channel diagnostics. Hosted by a i386-Linux PC in a crate with four available PCI slots, each single-PCI slot 32-channel digitiser features sampling frequencies up to 200 kHz, and 64 MB of memory, providing 1 Msample of 16-bit data per channel. The local hard disk is used for immediate local storage of all the acquired data from the selected channels into a local MDSplus database. The host is then accessed as a MDS/IP server that provides, on demand, down-sampled and software filtered traces. The local hard disk capacity is used for medium to long-term storage and availability of the full data set with optional mirror technology to guard against hard disk failure. We have thus obtained a general solution for high resolution, multi-channel routine acquisition using the multi-platform MDSplus environment, in which different software and hardware architectures are intelligently linked across a standard TCP/IP network. The implementation presented here uses ONLY standard components of the MDSplus environment

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.

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.

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice.

Science.gov (United States)

Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza

2012-01-06

Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

48 CFR 1532.003 - Simplified acquisition procedures financing.

Science.gov (United States)

2010-10-01

... procedures financing. 1532.003 Section 1532.003 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING 1532.003 Simplified acquisition procedures financing. (a) Scope. This subpart provides for authorization of advance and interim payments on...

An emotion-based view of acquisition integration capability

NARCIS (Netherlands)

Q.N. Huy (Quy N.); T.H. Reus (Taco)

2011-01-01

markdownabstractWe propose an emotion-based view of acquisition integration capability by developing an inter-firm model that focuses on dealing constructively with emotions during various organizational identification processes following mergers and acquisitions. The model describes diverse types

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...

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

Implementing Set Based Design into Department of Defense Acquisition

Science.gov (United States)

2016-12-01

The team employed a tailored waterfall process model in order to explore SBD applications in the support of defense acquisition and PORs. Figure 1...Engineering Model . Additionally, the team reviewed DOD case studies that implemented SBD. The SBD principles, along with the common themes from the...acquisition. 14. SUBJECT TERMS set based design, set based thinking, model based systems engineering, concurrent engineering, defense acquisition

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.

Graphical user interface for image acquisition and processing

Science.gov (United States)

Goldberg, Kenneth A.

2002-01-01

An event-driven GUI-based image acquisition interface for the IDL programming environment designed for CCD camera control and image acquisition directly into the IDL environment where image manipulation and data analysis can be performed, and a toolbox of real-time analysis applications. Running the image acquisition hardware directly from IDL removes the necessity of first saving images in one program and then importing the data into IDL for analysis in a second step. Bringing the data directly into IDL creates an opportunity for the implementation of IDL image processing and display functions in real-time. program allows control over the available charge coupled device (CCD) detector parameters, data acquisition, file saving and loading, and image manipulation and processing, all from within IDL. The program is built using IDL's widget libraries to control the on-screen display and user interface.

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

12 CFR 225.132 - Acquisition of assets.

Science.gov (United States)

2010-01-01

... it constitutes the acquisition, in whole or in part, of a going concern. 2 1 Section 225.4(c)(3) of... Regulation Y, the acquisition of a going concern requires prior Board approval. (c) The following examples... going concern. [39 FR 35128, Sept. 30, 1974, as amended at Reg. Y, 57 FR 28779, June 29, 1992] ...

Knowledge acquisition process as an issue in information sciences

Directory of Open Access Journals (Sweden)

Boris Bosančić

2016-07-01

Full Text Available The paper presents an overview of some problems of information science which are explicitly portrayed in literature. It covers the following issues: information explosion, information flood and data deluge, information retrieval and relevance of information, and finally, the problem of scientific communication. The purpose of this paper is to explain why knowledge acquisition, can be considered as an issue in information sciences. The existing theoretical foundation within the information sciences, i.e. the DIKW hierarchy and its key concepts - data, information, knowledge and wisdom, is recognized as a symbolic representation as well as the theoretical foundation of the knowledge acquisition process. Moreover, it seems that the relationship between the DIKW hierarchy and the knowledge acquisition process is essential for a stronger foundation of information sciences in the 'body' of the overall human knowledge. In addition, the history of both the human and machine knowledge acquisition has been considered, as well as a proposal that the DIKW hierarchy take place as a symbol of general knowledge acquisition process, which could equally relate to both human and machine knowledge acquisition. To achieve this goal, it is necessary to modify the existing concept of the DIKW hierarchy. The appropriate modification of the DIKW hierarchy (one of which is presented in this paper could result in a much more solid theoretical foundation of the knowledge acquisition process and information sciences as a whole. The theoretical assumptions on which the knowledge acquisition process may be established as a problem of information science are presented at the end of the paper. The knowledge acquisition process does not necessarily have to be the subject of epistemology. It may establish a stronger link between the concepts of data and knowledge; furthermore, it can be used in the context of scientific research, but on the more primitive level than conducting

A nuclear data acquisition system flow control model

International Nuclear Information System (INIS)

Hack, S.N.

1988-01-01

A general Petri Net representation of a nuclear data acquisition system model is presented. This model provides for the unique requirements of a nuclear data acquisition system including the capabilities of concurrently acquiring asynchronous and synchronous data, of providing multiple priority levels of flow control arbitration, and of permitting multiple input sources to reside at the same priority without the problem of channel lockout caused by a high rate data source. Finally, a previously implemented gamma camera/physiological signal data acquisition system is described using the models presented

Development of signal acquisition device of rotating coil measurement system

International Nuclear Information System (INIS)

Zhou Jianxin; Li Li; Kang Wen; Deng Chengdong; Yin Baogui; Fu Shinian

2013-01-01

A new rotating coil magnetic measurement system using the technical solution of the combination of a dynamic signal acquisition card and software with specific functions was developed. The acquisition device of the system successfully implemented the function of the PDI-5025 integrator. The sampling rate, the range, the accuracy and the flexibility of the system were improved. The development program of signal acquisition equipment, the realization of the acquisition function and the reliability and stability of the system were introduced. (authors)

EUROPEAN CROSS-BORDER MERGERS AND ACQUISITIONS- REALITIES AND PERSPECTIVES

Directory of Open Access Journals (Sweden)

Vancea Mariana

2011-07-01

Full Text Available This paper analyses the impact of the economic and financial crisis on merger and acquisition activity in Europe and the latest trends manifested on the cross-border merger and acquisition market involving European companies. Thus, a first objective of this research is to reveal the evolution of the European cross-border merger and acquisition activity in terms of dynamics, volume and structure. Another objective of this research is to reveal the short and medium term perspectives on mergers and acquisitions in Europe. Thus, under the continuous economic recovery of the European countries and the other worldwide economies, the recovery of financial markets and the growth of corporate profits, we shall witness an intensive cross-border merger and acquisition activity in Europe. The expansion engine of these operations seems to be represented by the emerging economies. This research is based on a systematic, logical and comparative analysis of scientific literature and statistical data regarding the cross-border mergers and acquisitions that involve European companies in recent years. This paper is part of the doctoral thesis Mergers and acquisitions- strategies of growth and development of enterprises. European and national particularities, coordinated by professor Ph.D. Alina Bădulescu from University of Oradea, Faculty of Economics. The doctoral research is supported by The Sectorial Operational Program for Human Resources Development 2007-2013, Contract POSDRU 59/1.5/S/1- Romanian researchers through modern and efficient doctoral programs.

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...

Information-dependent acquisition-mediated LC-MS/MS screening procedure with semiquantitative potential.

Science.gov (United States)

Decaestecker, Tineke N; Vande Casteele, Sofie R; Wallemacq, Pierre E; Van Peteghem, Carlos H; Defore, Dieter L; Van Bocxlaer, Jan F

2004-11-01

The development of a LC-MS/MS general unknown screening procedure for toxicologically relevant substances in blood samples by means of information-dependent acquisition on a Q-TOF is reported. IDA is an artificial intelligence-based product ion scan mode providing automatic "on-the-fly" MS to MS/MS switching. By performing information-dependent scanning at two different fragmentation energies, two collision-induced dissociation product ion spectra for each of the detected compounds are generated. As such, information-rich MS/MS spectra are obtained from precursor ions not known beforehand. In addition, limitation of the MS/MS acquisition time to an acceptable minimum resulted in an almost instantaneous switch back to the MS mode. As such, this approach provided MS chromatograms that still could be of use for semiquantitative purposes. Since the switching intensity threshold, unequivocally related to the background noise, proved a critical parameter, the solid-phase extraction procedure, the liquid chromatographic conditions, and the mass spectrometric parameters all were optimized to the advantage of information-dependent acquisition. Finally, the screening procedure we developed was benchmarked, on one hand, qualitatively against the results obtained from traditional GUS approaches in a number of routine toxicological laboratories (20 samples) and, on the other hand, quantitatively with respect to its potential against established LC-MS/MS methods (7 samples). The procedure performed very well from a qualitative point of view; almost all of the drugs detected by the conventional techniques were identified, as well as additional drugs that were not previously reported. The procedure proved well-suited for an initial semiquantitative assessment, as is customary in, for example, forensic toxicology before accurate intoxication levels are determined using targeted analytical analyses.