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Sample records for bortezomib velcaderegistered trademark

  1. Bortezomib.

    Science.gov (United States)

    Einsele, Hermann

    2014-01-01

    The ubiquitin-mediated degradation of proteins in numerous cellular processes, such as turnover and quality control of proteins, cell cycle and apoptosis, transcription and cell signaling, immune response and antigen presentation, and inflammation and development makes the ubiquitin-proteosome systems a very interesting target for various therapeutic interventions. Proteosome inhibitors were first synthesized as tools to probe the function and specificity of this particle's proteolytic activities. Most synthetic inhibitors rely on a peptide base, which mimics a protein substrate, attached at a COOH terminal "warhead." Notable warheads include boronic acids, such as bortezomib and epoxy ketones, such as carfilzomib. A variety of natural products also inhibit the proteosome that are not peptide-based, most notably lactacystin, that is related to NPI-0052, or salinosporamide A, another inhibitor in clinical trials. The possibility that proteosome inhibitors could be drug candidates was considered after studies showed that they induced apoptosis in leukemic cell lines. The first proteasome inhibitor in clinical application, bortezomib showed activity in non-small-cell lung and androgen-independent prostate carcinoma, as well as MM and mantle cell and follicular non-Hodgkin's lymphoma. It is now licensed for the treatment of newly diagnosed as well as relapsed/progressive MM and has had a major impact on the improvement in the treatment of MM in the last few years.

  2. Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma

    NARCIS (Netherlands)

    M.A. Dimopoulos (Meletios); R.Z. Orlowski (Robert); T. Facon (Thierry); P. Sonneveld (Pieter); K.C. Anderson (Kenneth); M. Beksaç (Meral); L. Benboubker (Lotfi); H. Roddie (Huw); A. Potamianou (Anna); C. Couturier (Catherine); O. Ataman (Ozlem); O. Ataman (Ozlem); H. van de Velde (Helgi); P.G. Richardson (P.)

    2014-01-01

    textabstractBortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib- dexamethasone and bortezomib using 109 propensity

  3. Bortezomib in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Rajeev Raghavan

    2010-01-01

    Full Text Available Although current therapies for pretransplant desensitization and treatment of antibody-mediated rejection (AMR have had some success, they do not specifically deplete plasma cells that produce antihuman leukocyte antigen (HLA antibodies. Bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma (a plasma cell neoplasm, induces plasma cell apoptosis. In this paper we review the current body of literature regarding the use of this biological agent in the field of transplantation. Although limited experience with bortezomib may seem to show promise in the realm of transplant recipients desensitization and treatment of AMR, there is also experience that may suggest otherwise. Bortezomib's role in desensitization protocols and treatment of AMR will be defined better as more clinical data and trials become available.

  4. Decon Green (trademark)

    National Research Council Canada - National Science Library

    Wagner, George W; Procell, Lawrence R; Henderson, Vikki D; Sorrick, David C; Hess, Zoe A; Gehring, David G; Brickhouse, Mark D

    2004-01-01

    ...) is extremely environmentally friendly and leaves no toxic residues. Decon Green (trademark) retains the low-temperature decontamination ability of DS2, but it is noncorrosive to aluminum and steel. Decon Green (trademark...

  5. License Agreements concerning trademarks

    OpenAIRE

    Dráb, Ladislav

    2014-01-01

    The thesis deals with license agreements in relation to trademarks, specially the trademark license agreement. The thesis contains in its theoretical interpretation of the concept and sources of the license agreement. There are also analyzed various types of license agreements, including modifying the license agreement in the new Civil Code, and related types of contracts as a franchising or merchandising. Another interpretation is more concerned with trademark and trademark license agreement...

  6. Problems of Trademark Licensing

    OpenAIRE

    Želvys, Arūnas

    2011-01-01

    Analysis of dissertation is focused on problematic aspects of trademark license agreement that exist throughout the conclusion, validity and termination of a contract. Problematic aspects are understood as legal interpretation cases where common and special norms have to be interpreted taking into account specifics of a contract object (right to a trademark). Problematic aspects are conditioned by two reasons: non comprehensive regulation of trademark license and sui generis nature of a contr...

  7. Bortezomib alters sour taste sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Akihiro Ohishi

    Full Text Available Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the control level on cessation of its administration. These results suggest that an increase in protein expression of PKD2L1 enhances the sour taste sensitivity in bortezomib-administered mice, and this alteration is reversed on cessation of its administration. Keywords: Taste disorder, Bortezomib, Sour taste, Chemotherapy, Adverse effect

  8. Bortezomib Induced Hepatitis B Reactivation

    Directory of Open Access Journals (Sweden)

    Salwa Hussain

    2014-01-01

    Full Text Available Background. It has recently been reported that hepatitis B (HBV reactivation often occurs after the use of rituximab and stem cell transplantation in patients with lymphoma who are hepatitis B surface antigen (HBsAg negative. However, clinical data on HBV reactivation in multiple myeloma (MM is limited to only a few reported cases. Bortezomib and lenalidomide have remarkable activity in MM with manageable toxicity profiles, but reactivation of viral infections may emerge as a problem. We present a case of MM that developed HBV reactivation after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with a history of marginal cell lymphoma was monitored without requiring therapy. In 2009, she developed MM, presenting as a plasmacytoma requiring vertebral decompression and focal radiation. While receiving radiation she developed renal failure and was started on bortezomib and liposomal doxorubicin. After a transient response to 5 cycles, treatment was switched to lenalidomide. Preceding therapy initiation, her serology indicated resolved infection. Serial monitoring for HBV displayed seroconversion one month after change in therapy. Conclusion. Bortezomib associated late HBV reactivation appears to be a unique event that requires further confirmation and brings to discussion whether hepatitis B core positive individuals would benefit from monitoring of HBV activation while on therapy.

  9. Nelfinavir augments proteasome inhibition by bortezomib in myeloma cells and overcomes bortezomib and carfilzomib resistance

    International Nuclear Information System (INIS)

    Kraus, M; Bader, J; Overkleeft, H; Driessen, C

    2013-01-01

    HIV protease inhibitors (HIV-PI) are oral drugs for HIV treatment. HIV-PI have antitumor activity via induction of ER-stress, inhibition of phospho-AKT (p-AKT) and the proteasome, suggesting antimyeloma activity. We characterize the effects of all approved HIV-PI on myeloma cells. HIV-PI were compared regarding cytotoxicity, proteasome activity, ER-stress induction and AKT phosphorylation using myeloma cells in vitro. Nelfinavir is the HIV-PI with highest cytotoxic activity against primary myeloma cells and with an IC 50 near therapeutic drug blood levels (8–14 μM), irrespective of bortezomib sensitivity. Only nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 μℳ. Ritonavir, saquinavir and lopinavir inhibited p-AKT comparable to nelfinavir, and showed similar synergistic cytotoxicity with bortezomib against bortezomib-sensitive cells. Nelfinavir had superior synergistic activity with bortezomib/carfilzomib in particular against bortezomib/carfilzomib-resistant myeloma cells. It inhibited not only the proteasomal β1/β5 active sites, similar to bortezomib/carfilzomib, but in addition the β2 proteasome activity not targeted by bortezomib/carfilzomib. Additional inhibition of β2 proteasome activity is known to sensitize cells for bortezomib and carfilzomib. Nelfinavir has unique proteasome inhibiting activity in particular on the bortezomib/carfilzomib-insensitive tryptic (β2) proteasome activity in intact myeloma cells, and is active against bortezomib/carfilzomib-resistant myeloma cells in vitro

  10. Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma

    Science.gov (United States)

    Dimopoulos, Meletios A.; Orlowski, Robert Z.; Facon, Thierry; Sonneveld, Pieter; Anderson, Kenneth C.; Beksac, Meral; Benboubker, Lotfi; Roddie, Huw; Potamianou, Anna; Couturier, Catherine; Feng, Huaibao; Ataman, Ozlem; van de Velde, Helgi; Richardson, Paul G.

    2015-01-01

    Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib-dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of any-grade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506. PMID:25261096

  11. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  12. Cardiotoxicity associated with bortezomib: A single-center experience

    Directory of Open Access Journals (Sweden)

    Murali Krishna Gurram

    2017-01-01

    Conclusion: Cardiotoxicity is probably not related to bortezomib, even though there are some case reports suggestive of cardiac events related to bortezomib. Our findings need to be confirmed in multicenter, prospective studies.

  13. Bortezomib

    Science.gov (United States)

    ... unusual bruising or bleeding black and tarry stools red blood in stools bloody vomit vomiting material that looks like coffee grounds slurred speech or inability to speak or understand speech loss of balance or coordination loss of memory paralysis (loss of ability to move a part ...

  14. Lasagna trademark soil remediation

    International Nuclear Information System (INIS)

    1996-04-01

    Lasagna trademark is an integrated, in situ remediation technology being developed which remediates soils and soil pore water contaminated with soluble organic compounds. Lasagna trademark is especially suited to sites with low permeability soils where electroosmosis can move water faster and more uniformly than hydraulic methods, with very low power consumption. The process uses electrokinetics to move contaminants in soil pore water into treatment zones where the contaminants can be captured and decomposed. Initial focus is on trichloroethylene (TCE), a major contaminant at many DOE and industrial sites. Both vertical and horizontal configurations have been conceptualized, but fieldwork to date is more advanced for the vertical configuration. Major features of the technology are electrodes energized by direct current, which causes water and soluble contaminants to move into or through the treatment layers and also heats the soil; treatment zones containing reagents that decompose the soluble organic contaminants or adsorb contaminants for immobilization or subsequent removal and disposal; and a water management system that recycles the water that accumulates at the cathode (high pH) back to the anode (low pH) for acid-base neutralization. Alternatively, electrode polarity can be reversed periodically to reverse electroosmotic flow and neutralize pH

  15. Bortezomib in the management of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jacob P Laubach

    2009-09-01

    Full Text Available Jacob P Laubach, Constantine S Mitsiades, Teru Hideshima, Robert Schlossman, Dharminder Chauhan, Nikhil Munshi, Irene Ghobrial, Nicole Carreau, Kenneth C Anderson, Paul G RichardsonDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USAAbstract: Multiple myeloma (MM is a B-cell malignancy characterized by clonal expansion of plasma cells within the bone marrow, the presence of a serum and/or urine monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the disease is characterized by complex interactions between tumor cells and the surrounding bone marrow microenvironment. Understanding of the relationship between malignant plasma cells and the microenvironment has sparked ongoing efforts to develop targeted therapeutic agents for treatment of this disease. The successful development of the first-in-class small-molecule proteasome inhibitor bortezomib occurred as a result of these efforts. This review focuses on the rationale for bortezomib therapy in the treatment of patients with newly diagnosed and relapsed MM, important treatment-related side effects, and future directions for use of bortezomib and other, emerging proteasome inhibitors.Keywords: multiple myeloma, bortezomib, stem cell transplantation, peripheral neuropathy

  16. Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.

    Science.gov (United States)

    Horton, Terzah M; Gannavarapu, Anurhadha; Blaney, Susan M; D'Argenio, David Z; Plon, Sharon E; Berg, Stacey L

    2006-07-01

    Although there is effective chemotherapy for many patients with leukemia, 20% of children and up to 65% of adults relapse. Novel therapies are needed to treat these patients. Leukemia cells are very sensitive to the proteasome inhibitor bortezomib (VELCADE(R), PS-341), which enhances the in vitro cytotoxic effects of dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib enhances the cytotoxicity of agents used in leukemia, we employed an in vitro tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin, cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor HA14.1. We demonstrated that primary leukemia lymphoblasts and leukemia cell lines are sensitive to bortezomib, with an average IC(50) of 12 nM. Qualitative and quantitative bortezomib-drug interactions were evaluated using the universal response surface approach (URSA). Bortezomib was synergistic with dexamethasone in dexamethasone-sensitive leukemia cells, and additive with vincristine, asparaginase, cytarabine, and doxorubicin. The anti-leukemic activity of bortezomib was also additive with geldanamycin and HA14.1, and additive or synergistic with trichostatin A. These results were compared to analysis using the median-dose effect method, which generated complex drug interactions due to differences in dose-response curve sigmoidicities. These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia.

  17. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  18. Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting ...

    African Journals Online (AJOL)

    1The Lishui People's Hospital, Lishui 324000, 2Department of Hematology, First Affiliated Hospital, Zhejiang University College ... concentrations of curcumin alone and also combined with 0.01 mM bortezomib. ... effects(viability inhibition and apoptosis induction increased (p < 0.05), whereas bortezomib alone had.

  19. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  20. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy

    Directory of Open Access Journals (Sweden)

    Morgan Gareth

    2005-06-01

    Full Text Available Abstract Bortezomib is a highly selective, reversible inhibitor of the 26S proteasome that is indicated for single-agent use in the treatment of patients with multiple myeloma who have received at least 2 prior therapies and are progressing on their most recent therapy. Clinical investigations have been completed or are under way to evaluate the safety and efficacy of bortezomib alone or in combination with chemotherapy in multiple myeloma, both at relapse and presentation, as well as in other cancer types. The antiproliferative, proapoptotic, antiangiogenic, and antitumor activities of bortezomib result from proteasome inhibition and depend on the altered degradation of a host of regulatory proteins. Exposure to bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1, and inhibitor κB-α, which prevents activation of nuclear factor κB-induced cell survival pathways. Bortezomib also promoted the activation of the proapoptotic c-Jun-NH2 terminal kinase, as well as the endoplasmic reticulum stress response. The anticancer effects of bortezomib as a single agent have been demonstrated in xenograft models of multiple myeloma, adult T-cell leukemia, lung, breast, prostate, pancreatic, head and neck, and colon cancer, and in melanoma. In these preclinical in vivo studies, bortezomib treatment resulted in decreased tumor growth, angiogenesis, and metastasis, as well as increased survival and tumor apoptosis. In several in vitro and/or in vivo cancer models, bortezomib has also been shown to enhance the antitumor properties of several antineoplastic treatments. Importantly, bortezomib was generally well tolerated and did not appear to produce additive toxicities when combined with other therapies in the dosing regimens used in these preclinical in vivo investigations. These findings provide a rationale for further clinical trials using bortezomib alone or in combination regimens with

  1. Trademark Values in Corporate Restructuring

    OpenAIRE

    Torres, Fernando

    2007-01-01

    In corporate restructuring under Chapter 11, an asset valuation is a central task for both legal and financial reasons. In the area of intangible assets, however, generally accepted accounting principles (GAAP) do not reflect internally-generated assets such as brands, trademarks, and other intellectual property. In practice, arbitrary rules of thumb are used to fill this gap, and closure, liquidation, financing, and restructuring decisions are made on this basis. This paper reports the ...

  2. Bortezomib induces autophagic death in proliferating human endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Belloni, Daniela; Veschini, Lorenzo [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Foglieni, Chiara [Department of Cardiology, IRCCS H San Raffaele, Milan (Italy); Dell' Antonio, Giacomo [Department of Pathology, IRCCS H San Raffaele, Milan (Italy); Caligaris-Cappio, Federico [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Universita Vita-Salute IRCCS H San Raffaele, Milan (Italy); Ferrarini, Marina [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy); Ferrero, Elisabetta, E-mail: elisabetta.ferrero@hsr.it [Myeloma Unit, Department of Oncology, IRCCS H San Raffaele, Milan (Italy)

    2010-04-01

    The proteasome inhibitor Bortezomib has been approved for the treatment of relapsed/refractory multiple myeloma (MM), thanks to its ability to induce MM cell apoptosis. Moreover, Bortezomib has antiangiogenic properties. We report that endothelial cells (EC) exposed to Bortezomib undergo death to an extent that depends strictly on their activation state. Indeed, while quiescent EC are resistant to Bortezomib, the drug results maximally toxic in EC switched toward angiogenesis with FGF, and exerts a moderate effect on subconfluent HUVEC. Moreover, EC activation state deeply influences the death pathway elicited by Bortezomib: after treatment, angiogenesis-triggered EC display typical features of apoptosis. Conversely, death of subconfluent EC is preceded by ROS generation and signs typical of autophagy, including intense cytoplasmic vacuolization with evidence of autophagosomes at electron microscopy, and conversion of the cytosolic MAP LC3 I form toward the autophagosome-associated LC3 II form. Treatment with the specific autophagy inhibitor 3-MA prevents both LC3 I/LC3 II conversion and HUVEC cell death. Finally, early removal of Bortezomib is accompanied by the recovery of cell shape and viability. These findings strongly suggest that Bortezomib induces either apoptosis or autophagy in EC; interfering with the autophagic response may potentiate the antiangiogenic effect of the drug.

  3. The protective effects of lafutidine for bortezomib induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Tsukaguchi M

    2013-07-01

    Full Text Available Machiko Tsukaguchi, Masaru Shibano, Ai Matsuura, Satoru MukaiDepartment of Hematology,Sakai City Hospital, Osaka, JapanAbstract: Peripheral neuropathy (PN caused by bortezomib is an important complication of multiple myeloma. Subcutaneous injection of bortezomib reduced PN, but 24% of cases were grade 2 PN and 6% of cases were grade 3 PN. PN higher than grade 2 was not resolved by subcutaneous injection. PN higher than grade 3 has serious dose limiting toxicity and is the cause of discontinuing bortezomib treatment. Lafutidine is an H2-blocker with gastroprotective activity and is thought to function by increasing mucosal blood flow via capsaicin sensitive neurons. The same activity of lafutidine is considered to improve glossodynia and taxane induced PN. We hypothesized that lafutidine prevents or improves PN that is caused by bortezomib. In the current study, bortezomib was administered in the usual manner (intravenous administration of bortezomib 1.3 mg/m2, twice a week for 2 weeks, followed by 1 week without treatment for up to four cycles to compare our data with other studies. Lafutidine was administered orally at a dose of 10 mg twice daily. In our eight evaluated cases, the total occurrence of PN was four out of eight patients (50%. There were only grade 1 PN (4 out of 8 cases, and no cases higher than grade 2. We conclude that (1 the total occurrence of PN was not improved, (2 there was no PN after the first course, (3 there were only grade 1 cases and there were no cases higher than grade 2, and (4 no cases discontinued bortezomib treatment because of PN. This is the first report showing that lafutidine is useful for the amelioration of bortezomib induced PN.Keywords: bortezomib induced peripheral neuropathy, lafutidine, capsaicin sensitive neurons, calcitonin gene-related peptide, transient receptor potential 1, multiple myeloma

  4. Convergence of Copyright and Trademark Protection

    OpenAIRE

    Holub, Lukáš

    2016-01-01

    Convergence of Copyright and Trademark Protection Key Words: Copyright, Trademark, Protection, Convergence Abstract: The thesis analyzes the concept of copyright and trademark protection in Czech law and the consequences of their simultaneous operation. The aim is to determine whether the existing legislation responds the current trends and demands in our society, where business and arts are becoming interconnected and where the boundaries between those disciplines are blurred. Both protectio...

  5. Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy.

    Science.gov (United States)

    Berenson, J R; Hilger, J D; Yellin, O; Dichmann, R; Patel-Donnelly, D; Boccia, R V; Bessudo, A; Stampleman, L; Gravenor, D; Eshaghian, S; Nassir, Y; Swift, R A; Vescio, R A

    2014-07-01

    In this open-label, intra-patient phase I/II trial, bortezomib was replaced with carfilzomib (escalated from 20 to 45 mg/m(2) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle) for multiple myeloma (MM) patients who progressed while on or within 12 weeks of receiving a bortezomib-containing combination regimen. Study objectives included determination of the maximum tolerated dose (MTD), overall response rate (ORR), clinical benefit rate (CBR), time to progression, time to response, duration of response, progression-free survival and overall survival (OS). Of 38 registered patients, 37 were treated and evaluable for efficacy and safety. Thirty-one carfilzomib-based regimens using 14 different drug combinations were tested. One regimen (carfilzomib (45 mg/m(2)), ascorbic acid (1000 mg) and cyclophosphamide (2.2 mg/kg)) reached MTD. ORR and CBR were 43.2 and 62.2%, respectively. Median progression-free survival, time to progression and OS were 8.3, 9.9 and 15.8 months, respectively. Hematologic adverse events (AEs; ⩾grade 3) included lymphopenia (35.1%), thrombocytopenia (24.3%), anemia (10.8%) and neutropenia (10.8%). Nonhematologic AEs (⩾grade 3) included fever (5.4%) and hypokalemia (5.4%). These results demonstrate that replacing bortezomib with carfilzomib is safe and can be effective for MM patients failing bortezomib-containing combination regimens. This trial was registered at http://www.clinicaltrials.gov (#NCT01365559).

  6. Trademark Licensing in Keyword Advertising

    OpenAIRE

    Zejda, Maciej

    2016-01-01

    This article examines the use of trademarks as keywords in sponsored links campaigns - in particular the impact of such usage on consumer confusion. It is thus important to highlight that there are a number of reasons why a consumer uses search engines. For example, it may be that a consumer searches for a type of product or service that appeals to them; the consumer may engage in comparison-shopping; or the consumer may already know the specific brand that he or she intends to purchase. Seco...

  7. 76 FR 72000 - Patent, Trademark & Copyright Acts

    Science.gov (United States)

    2011-11-21

    ... DEPARTMENT OF THE INTERIOR Geological Survey Patent, Trademark & Copyright Acts AGENCY: U.S... Consultants, 1255 Roberts Boulevard NW., Suite 200, Kennesaw, GA 30144, on U.S. Patent Application Serial No. 12/133,666, and a divisional patent application to be filed shortly at the Patent and Trademark...

  8. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation

    DEFF Research Database (Denmark)

    Pérez-Galán, Patricia; Mora-Jensen, Helena; Weniger, Marc A

    2011-01-01

    Bortezomib induces remissions in 30%-50% of patients with relapsed mantle cell lymphoma (MCL). Conversely, more than half of patients' tumors are intrinsically resistant to bortezomib. The molecular mechanism of resistance has not been defined. We generated a model of bortezomib-adapted subclones...

  9. 19 CFR 133.21 - Articles bearing counterfeit trademarks.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles bearing counterfeit trademarks. 133.21... Recorded Trademarks or Recorded Trade Names § 133.21 Articles bearing counterfeit trademarks. (a... substantially indistinguishable from, a registered trademark. (b) Seizure. Any article of domestic or foreign...

  10. 76 FR 34062 - Patent and Trademark Financial Transactions

    Science.gov (United States)

    2011-06-10

    ... DEPARTMENT OF COMMERCE Patent and Trademark Office Patent and Trademark Financial Transactions ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and Trademark Office... Information Officer, United States Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450...

  11. 7 CFR 1250.542 - Patents, copyrights, trademarks, and information.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, trademarks, and information... AGRICULTURE EGG RESEARCH AND PROMOTION Rules and Regulations Patents, Copyrights, Trademarks, and Information § 1250.542 Patents, copyrights, trademarks, and information. Patents, copyrights, trademarks, and...

  12. Clothing creator trademark : Business plan

    Energy Technology Data Exchange (ETDEWEB)

    Stern, B.

    1990-10-01

    SYMAGERY has developed a patented process to manufacture clothing without direct human labor. This CLOTHING CREATOR{trademark}, will have the ability to produce two (2) perfect garments every 45 seconds or one (1) every 30 seconds. The process will combine Computer Integrated Manufacturing (CIM) technology with heat molding and ultrasonic bonding/cutting techniques. This system for garment production, will have the capacity to produce garments of higher quality and at lower productions costs than convention cut and sew methods. ADVANTAGES of the process include: greatly reduced production costs; increased quality of garments; reduction in lead time; and capacity to make new class of garments. This technology will accommodate a variety of knit, woven and nonwoven materials containing a majority of synthetic fibers. Among the many style of garments that could be manufactured by this process are: work clothing, career apparel, athletic garments, medical disposables, health care products, activewear, haz/mat garments, military clothing, cleanroom clothing, outdoor wear, upholstery, and highly contoured stuffed toy shells. 3 refs.

  13. ALARA trademark 1146 strippable coating

    International Nuclear Information System (INIS)

    Fricke, V.

    1999-01-01

    Strippable or temporary coatings are innovative technologies for decontamination that effectively reduce loose contamination at low cost. These coatings have become a viable option during the deactivation and decommissioning of both US Department of Energy (DOE) and commercial nuclear facilities to remove or fix loose contamination on both vertical and horizontal surfaces. The ALARA trademark 1146 strippable coating was demonstrated as part of the Savannah River Site LSDDP and successfully removed transferable (surface) contamination from multiple surfaces (metal and concrete) with an average decontamination factor for alpha contamination of 6.68 and an average percentage of alpha contamination removed of 85.0%. Beta contamination removed was an average DF of 5.55 and an average percentage removed of 82.0%. This paper is an Innovative Technology Summary Report designed to provide potential users with the information they need to quickly determine if a technology would apply to a particular environmental management problem. They also are designed for readers who may recommend that a technology be considered by prospective users. This Innovative Technology offers a 35% cost savings over the Baseline Technology

  14. Trademark Licensing Agreements in Light of the EC Competition Rules

    OpenAIRE

    Machnicka, Agnieszka A.

    2008-01-01

    Introduction. Part I.- The notion of trademark licensing agreements and their uses: 1. Definition of trademark licensing agreements. 1.2. EC Trademark licensing provisions. 1.3. Other trademark agreements ¿ mention. 1.4. Relevant competition law provisions. Part II.- 2. Individual contractual clauses within the prohibition of art. 81(1) EEC Treaty: 2.1. Territorial protection, exclusive licensing 2.1.1. Exclusivity in trademark licensing ¿ general remarks. 2.1.2. Specific ci...

  15. An Interdisciplinary Inquiry into the Foundations of Trademark Law

    Directory of Open Access Journals (Sweden)

    Sh. Kasnavi

    2016-05-01

    Full Text Available The assessment of any legal system, such as trademark law, requires a comprehensive understanding of that system, and this can be made possible only through awareness of the objectives and foundations of that system. This awareness in trademark law helps us interpret better, especially where there are no statutes. Trademark law is highly influenced by both moral and legal issues and the basics of market economy because trademark has fully economic dimensions as well, and the existence of trademark depends on the economic efficiency of the market. This highlights the necessity of an interdisciplinary approach with the aim of understanding this supportive system. Natural law theory and contractual theory legally justify the protection of trademark. Beside these two theories, the search cost theory and incentive of producers, as two important economic factors, justify the protection of trademark even more powerfully. Nonetheless, trademark legal system relies on all these foundations and each of them is necessary to interpret trademark law.

  16. Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting ...

    African Journals Online (AJOL)

    Purpose: To investigate whether curcumin augments bortezomib-induced apoptosis in myeloma cells (MM1.R line), and to explore the molecular mechanism with regard to heat shock protein 90 (HSP90) expression. Methods: MTT cell viability assay was used to assess growth inhibition of MM1.R cells at different ...

  17. Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes

    Directory of Open Access Journals (Sweden)

    Vallumsetla N

    2015-11-01

    Full Text Available Nishanth Vallumsetla, Jonas Paludo, Prashant Kapoor Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Mantle cell lymphoma (MCL is an incurable, typically aggressive subtype of non-Hodgkin lymphoma, accounting for 4%–7% of newly diagnosed non-Hodgkin lymphoma cases. Chemoresistance commonly ensues in MCL, and patients with this heterogeneous disease invariably relapse, underscoring the unmet need for better therapies. Over the past few years, several novel agents with promising activity and unique mechanisms of action have been deemed effective in MCL. Bortezomib is a reversible proteasome inhibitor, approved as a single agent for patients with relapsed/refractory MCL who have received at least one prior line of therapy. Addition of bortezomib to chemoimmunotherapies has demonstrated good tolerability and superior efficacy, both in the upfront and salvage settings, and recently one such combination of bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone was approved as a frontline regimen in untreated patients with MCL. This review examines the role of bortezomib in a multitude of clinical settings and ongoing clinical trials designed to optimize its integration in the current treatment paradigms of MCL. Keywords: non-Hodgkin lymphoma, proteosome inhibitor, treatment

  18. Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib.

    Directory of Open Access Journals (Sweden)

    Julia S Gelman

    Full Text Available Bortezomib is an antitumor drug that competitively inhibits proteasome beta-1 and beta-5 subunits. While the impact of bortezomib on protein stability is known, the effect of this drug on intracellular peptides has not been previously explored. A quantitative peptidomics technique was used to examine the effect of treating human embryonic kidney 293T (HEK293T cells with 5-500 nM bortezomib for various lengths of time (30 minutes to 16 hours, and human neuroblastoma SH-SY5Y cells with 500 nM bortezomib for 1 hour. Although bortezomib treatment decreased the levels of some intracellular peptides, the majority of peptides were increased by 50-500 nM bortezomib. Peptides requiring cleavage at acidic and hydrophobic sites, which involve beta-1 and -5 proteasome subunits, were among those elevated by bortezomib. In contrast, the proteasome inhibitor epoxomicin caused a decrease in the levels of many of these peptides. Although bortezomib can induce autophagy under certain conditions, the rapid bortezomib-mediated increase in peptide levels did not correlate with the induction of autophagy. Taken together, the present data indicate that bortezomib alters the balance of intracellular peptides, which may contribute to the biological effects of this drug.

  19. Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Sachin Diwadkar

    2016-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

  20. Skin dose measurement with MICROSPEC-2 trademark

    International Nuclear Information System (INIS)

    Hsu, H.H.

    1997-01-01

    For many years, the Eberline HP-260 trademark beta detectors were used for skin dose measurements at Los Alamos National Laboratory. This detector does not measure the beta spectrum and the skin dose can only be determined if the contaminating radioactive isotope is known. A new product MICROSPEC-2 trademark, has been developed which consists of a small portable computer with a multichannel analyzer and a beta probe consisting of a phoswich detector. The system measures the beta spectrum and automatically folds in the beta fluence-to-dose conversion function to yield the skin dose

  1. Mast-sipping in EPR trademark plants

    International Nuclear Information System (INIS)

    Langenberger, Jan; Schienbein, Marcel; Geier, Roland

    2010-01-01

    For more than 20 years, AREVA applies and develops different sipping techniques to identify fuel assemblies with leaking fuel rods. For the EPR trademark reactors a Mast Sipping System with newest developments will be implemented considering radiation protection and latest standards requirements. The innovative EPR trademark Sipping System differs from previous systems in many ways. One of the main innovations is that all the necessary processes of the Sipping system have been fully digitized. Second, several ALARA design modifications have been implemented to meet the current radiation protection requirements. An additional implementable multilingual assistance program facilitates the handling of the system and helps to prevent incorrect operation. (orig.)

  2. Chalazia Development in Multiple Myeloma: A New Complication Associated with Bortezomib Therapy

    Science.gov (United States)

    Yun, Charles; Mukhi, Nikhil; Kremer, Valerie; Shinder, Roman; Verma, Vaibhav; Olcay, Batuman

    2015-01-01

    Multiple myeloma (MM) is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia – which caused intolerable discomfort – started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia. PMID:26330998

  3. Chalazia development in multiple myeloma: a new complication associated with bortezomib therapy

    Directory of Open Access Journals (Sweden)

    Charles Yun

    2015-06-01

    Full Text Available Multiple myeloma (MM is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia − which caused intolerable discomfort − started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia.

  4. Trypanocidal activity of the proteasome inhibitor and anti-cancer drug bortezomib

    Directory of Open Access Journals (Sweden)

    Wang Xia

    2009-07-01

    Full Text Available Abstract The proteasome inhibitor and anti-cancer drug bortezomib was tested for in vitro activity against bloodstream forms of Trypanosoma brucei. The concentrations of bortezomib required to reduce the growth rate by 50% and to kill all trypanosomes were 3.3 nM and 10 nM, respectively. In addition, bortezomib was 10 times more toxic to trypanosomes than to human HL-60 cells. Moreover, exposure of trypanosomes to 10 nM bortezomib for 16 h was enough to kill 90% of the parasites following incubation in fresh medium. However, proteasomal peptidase activities of trypanosomes exposed to bortezomib were only inhibited by 10% and 30% indicating that the proteasome is not the main target of the drug. The results suggest that bortezomib may be useful as drug for the treatment of human African trypanosomiasis.

  5. 78 FR 61185 - Patent and Trademark Office Acquisition Guidelines (PTAG)

    Science.gov (United States)

    2013-10-03

    ... site. Part 3--Electronic Commerce The USPTO will use governmentwide acquisition systems to the maximum... DEPARTMENT OF COMMERCE United States Patent and Trademark Office 37 CFR Chapter I [Docket No.: PTO... and Trademark Office, Commerce. ACTION: Notice. SUMMARY: The United States Patent and Trademark Office...

  6. 76 FR 53885 - Patent and Trademark Resource Centers Metrics

    Science.gov (United States)

    2011-08-30

    ... DEPARTMENT OF COMMERCE United States Patent and Trademark Office Patent and Trademark Resource Centers Metrics ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and... ``Patent and Trademark Resource Centers Metrics comment'' in the subject line of the message. Mail: Susan K...

  7. 75 FR 35973 - Trademark Technical and Conforming Amendments

    Science.gov (United States)

    2010-06-24

    ... allow all trademark owners to cure deficiencies in their maintenance filings, including when the..., VA 22313-1451, attention Cynthia Lynch; by hand-delivery to the Trademark Assistance Center... maintenance filings to the USPTO. In addition, the legislation allows all trademark owners to cure...

  8. Patents, trademarks, and their complementarity in venture capital funding

    NARCIS (Netherlands)

    Zhou, Haibo; Sandner, Philipp G.; Martinelli, Simon Luca; Block, Joern H.

    This paper analyzes the effects of patents and trademarks in the financing of start-ups through venture capitalists (VCs). Patents and trademarks signal a start-up's technological and marketing capabilities. We find that patents and trademarks not only have direct effects on venture capital

  9. Licensing of College and University Trademarks.

    Science.gov (United States)

    Anderson, David A.

    1981-01-01

    Under trademark law a school automatically develops rights in the use of its name, athletic team, names and slogans, and seals and symbols, but federal registration is also available. Registration provides both national constructive notice of the claim of rights and incontestability of rights after five years of continuous use. (MSE)

  10. A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy

    NARCIS (Netherlands)

    Lieu, Christopher; Chow, Laura; Pierson, A. Scott; Eckhardt, S. Gail; O'Bryant, Cindy L.; Morrow, Mark; Tran, Zung Vu; Wright, John J.; Gore, Lia

    Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. Patients and methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days.

  11. Herpes zoster in multiple myeloma patients during bortezomib treatment

    Directory of Open Access Journals (Sweden)

    I. N. Nazarova

    2011-01-01

    Full Text Available Recent advances in multiple myeloma (MM treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.

  12. Biomedical technology prosperity game{trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Berman, M.; Boyack, K.W.; Wesenberg, D.L.

    1996-07-01

    Prosperity Games{trademark} are an outgrowth and adaptation of move/countermove and seminar War Games. Prosperity Games{trademark} are simulations that explore complex issues in a variety of areas including economics, politics, sociology, environment, education and research. These issues can be examined from a variety of perspectives ranging from a global, macroeconomic and geopolitical viewpoint down to the details of customer/supplier/market interactions in specific industries. All Prosperity Games{trademark} are unique in that both the game format and the player contributions vary from game to game. This report documents the Biomedical Technology Prosperity Game{trademark} conducted under the sponsorship of Sandia National Laboratories, the Defense Advanced Research Projects Agency, and the Koop Foundation, Inc. Players were drawn from all stakeholders involved in biomedical technologies including patients, hospitals, doctors, insurance companies, legislators, suppliers/manufacturers, regulators, funding organizations, universities/laboratories, and the legal profession. The primary objectives of this game were to: (1) Identify advanced/critical technology issues that affect the cost and quality of health care. (2) Explore the development, patenting, manufacturing and licensing of needed technologies that would decrease costs while maintaining or improving quality. (3) Identify policy and regulatory changes that would reduce costs and improve quality and timeliness of health care delivery. (4) Identify and apply existing resources and facilities to develop and implement improved technologies and policies. (5) Begin to develop Biomedical Technology Roadmaps for industry and government cooperation. The deliberations and recommendations of these players provided valuable insights as to the views of this diverse group of decision makers concerning biomedical issues. Significant progress was made in the roadmapping of key areas in the biomedical technology field.

  13. Trademark Licensing in a Monopolistically Competitive Industry

    OpenAIRE

    Martin K. Perry; Robert H. Groff

    1986-01-01

    This article examines the efficacy of intrabrand rivalry in a monopolistically competitive industry. Intrabrand rivalry through trademark licensing would result in lower prices for consumers, but would also reduce product diversity because all brands would be less profitable. Using both the constant elasticity of substitution and the spatial models of product differentiation, we find that when fixed costs are specific to each firm, the welfare losses on product diversity dominate the welfare ...

  14. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

    International Nuclear Information System (INIS)

    Wang, Cun; Jin, Guangzhi; Sun, Haiyan; Wu, Weizhong; Liu, Yinkun; Gao, Dongmei; Guo, Kun; Kang, Xiaonan; Jiang, Kai; Sun, Chun; Li, Yan; Sun, Lu; Shu, Hong

    2012-01-01

    Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR) has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth inhibition (72.4%), comparing with either rapamycin- (54.7%) or

  15. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

    Directory of Open Access Journals (Sweden)

    Wang Cun

    2012-05-01

    Full Text Available Abstract Background Despite recent advances in the treatment of hepatocellular carcinoma (HCC, the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. Methods The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Results Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth

  16. Trade name and trademark versus domain

    Directory of Open Access Journals (Sweden)

    Jarmila Pokorná

    2013-01-01

    Full Text Available Internet domains have become an integral part of our lives, so one can easily understand that during their use, conflicts can arise, whose participants will search for rules enabling resolution of conflicts. Since the domain name is a replacement of the computer IP address, in the technical sense of the word, this does not concern for domain names a commercial name or brand, because it primarily does not belong to a person in the legal sense of the word and does not serve for its individualization. The average user regularly affiliates domain names with a person offering goods or services on the relevant Website. Domain names used by entrepreneurs in their business activity are often chosen so that the second-level domain (SLD would use words that form the trade name of corporations formed of trading companies. This fact brings domain names close to such designations that serve the individualization of persons or products, especially the trademarks and the commercial name. Domains can come into conflict with the rights to designations, especially trademarks and commercial names. Court practice is resolving these conflicts using rules for unfair competition, or rules for protection of commercial names and trademarks, but it is not ruled out that in the future, special legal regulation of domain names could be established.

  17. Praktik Trademark Squatting dalam Proses Pendaftaran Merek di Indonesia

    Directory of Open Access Journals (Sweden)

    Widya Justitia

    2016-04-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui dan menganalisis mengapa praktik trademark squatting dapat terjadi dalam proses pendaftaran merek beserta cara mengatasinya. Selanjutnya, penelitian ini juga membahas mengenai konsepsi ideal terkait proses pendaftaran merek di Indonesia guna menghindari dan meminimalisasi praktik trademark squatting. Penelitian ini merupakan penelitian kualitatif yang bersifat yuridis empiris dan data yang terkumpul dianalisa dengan metode deskriptif kualitatif. Hasil penelitian menunjukkan bahwa praktik trademark squatting merupakan suatu tindakan mendaftarkan merek milik orang lain yang belum terdaftar, sehingga membuat pemilik merek yang sebenarnya tidak dapat lagi mendaftarkan mereknya. Setelah itu, pelaku menjual sertifikat hak atas merek tersebut kepada pemilik aslinya dengan harga melebihi biaya permohonan pendaftaran merek pada umumnya. Kendala yang ditemui dalam proses pendaftaran merek di Indonesia adalah kurangnya sumber daya manusia dalam menangani jumlah permohonan pendaftaran merek yang mencapai ribuan setiap harinya. Hal ini berdampak pada tidak optimalnya proses pendaftaran merek di Indonesia yaitu dengan menggagas suatu sistem yang bernama first to file based on use guna mengoptimalisasikan perlindungan pemilik merek, pertimbangan untuk meratifikasi Madrid System juga merupakan salah satu opsi lain untuk mencegah praktik trademark squatting. Abstract The purpose of this research is to identify and analyze why the practice of trademark squatting could occur in Indonesia's trademark registration process along with the constraints found in the trademark registration process in Indonesia and how to overcome them. Furthermore, it will also discuss the ideal conception related to trademark registration process to avoid and minimize the practice of trademark squatting. This research is an empirical legal research and all data were analyzed with qualitative methods. The results showed that trademark squatting is

  18. Bortezomib Prescription Pattern for the Treatment of Multiple Myeloma by Hematologists in Nigeria

    Directory of Open Access Journals (Sweden)

    Kaladada I. Korubo

    2017-10-01

    Full Text Available Purpose: Novel therapy has dramatically changed the outcome of patients with myeloma. Current National Comprehensive Cancer Network guidelines give bortezomib-based combinations a central role in the management of multiple myeloma (MM. The aim of this survey is to assess the use of bortezomib for the treatment of MM by hematologists practicing in Nigeria. Materials and Methods: This is a cross-sectional observational survey. A structured, prevalidated questionnaire was self-administered to different cadres of hematologists. Data collected were analyzed using SPSS software version 21 (IBM, Chicago, IL. Results: There were 54 respondents from 24 centers across the country. The most frequently used drugs for first-line therapy were thalidomide (66.7%, dexamethasone (54.2%, and bortezomib (48%, and a combination of bortezomib, thalidomide, and dexamethasone (16.7% was the most frequently used first-line regimen. Of the 54 hematologists, 39 (72.2% had prescribed bortezomib previously; no one had used bortezomib as monotherapy. Drug unavailability (86.7% and cost (46.7% were the major reasons for those who had not prescribed bortezomib. Approximately 56.4% of responders had patients who had experienced adverse effects, of which neuropathy was the most common (86.3%. Conclusion: Bortezomib, thalidomide, and dexamethasone was the most frequently used first-line regimen to treat myelomatosis. Thalidomide and dexamethasone were the most frequently used drugs in myeloma treatment. Despite poor access to health care, coupled with the high cost and poor availability of bortezomib in our low- or middle-income country, those who prescribed bortezomib did so frequently (in more than half of their patients.

  19. Bortezomib is cytotoxic to the human growth plate and permanently impairs bone growth in young mice.

    Directory of Open Access Journals (Sweden)

    Emma Eriksson

    Full Text Available Bortezomib, a novel proteasome inhibitor approved for the treatment of cancer in adults, has recently been introduced in pediatric clinical trials. Any tissue-specific side effects on bone development have to our knowledge not yet been explored. To address this, we experimentally studied the effects of bortezomib in vivo in young mice and in vitro in organ cultures of rat metatarsal bones and human growth plate cartilage, as well as in a rat chondrocytic cell line. We found that bortezomib while efficiently blocking the ubiquitin/proteasome system (UPS caused significant growth impairment in mice, by increasing resting/stem-like chondrocyte apoptosis. Our data support a local action of bortezomib, directly targeting growth plate chondrocytes leading to decreased bone growth since no suppression of serum levels of insulin-like growth factor-I (IGF-I was observed. A local effect of bortezomib was confirmed in cultured rat metatarsal bones where bortezomib efficiently caused growth retardation in a dose dependent and irreversible manner, an effect linked to increased chondrocyte apoptosis, mainly of resting/stem-like chondrocytes. The cytotoxicity of bortezomib was also evaluated in a unique model of cultured human growth plate cartilage, which was found to be highly sensitive to bortezomib. Mechanistic studies of apoptotic pathways indicated that bortezomib induced activation of p53 and Bax, as well as cleavage of caspases and poly-ADP-ribose polymerase (PARP in exposed chondrocytes. Our observations, confirmed in vivo and in vitro, suggest that bone growth could potentially be suppressed in children treated with bortezomib. We therefore propose that longitudinal bone growth should be closely monitored in ongoing clinical pediatric trials of this promising anti-cancer drug.

  20. Verification and validation of decision support software: Expert Choice{trademark} and PCM{trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Q.H.; Martin, J.D.

    1994-11-04

    This report documents the verification and validation of two decision support programs: EXPERT CHOICE{trademark} and PCM{trademark}. Both programs use the Analytic Hierarchy Process (AHP) -- or pairwise comparison technique -- developed by Dr. Thomas L. Saaty. In order to provide an independent method for the validating the two programs, the pairwise comparison algorithm was developed for a standard mathematical program. A standard data set -- selecting a car to purchase -- was used with each of the three programs for validation. The results show that both commercial programs performed correctly.

  1. Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types

    Directory of Open Access Journals (Sweden)

    Chanan-Khan Asher A

    2010-01-01

    Full Text Available Abstract Background Survivin is known playing a role in drug resistance. However, its role in bortezomib-mediated inhibition of growth and induction of apoptosis is unclear. There are conflicting reports for the effect of bortezomib on survivin expression, which lacks of a plausible explanation. Methods: In this study, we tested cancer cells with both p53 wild type and mutant/null background for the relationship of bortezomib resistance with survivin expression and p53 status using MTT assay, flow cytometry, DNA fragmentation, caspase activation, western blots and RNAi technology. Results We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. However, silencing of survivin expression utilizing survivin mRNA-specific siRNA/shRNA in p53 mutant or null cells sensitized cancer cells to bortezomib mediated apoptosis induction, suggesting a role for survivin in bortezomib resistance. We further noted that modulation of survivin expression by bortezomib is dependent on p53 status but independent of cancer cell types. In cancer cells with mutated p53 or p53 null, bortezomib appears to induce survivin expression, while in cancer cells with wild type p53, bortezomib downregulates or shows no significant effect on survivin expression, which is dependent on the drug concentration, cell line and exposure time. Conclusions Our findings, for the first time, unify the current inconsistent findings for bortezomib treatment and survivin expression, and linked the effect of bortezomib on survivin expression, apoptosis induction and bortezomib resistance in the relationship with p53 status, which is independent of cancer cell types. Further mechanistic studies along with this line may impact the optimal clinical application of bortezomib in

  2. Neuropathic pain in cancer patients treated with bortezomib.

    Science.gov (United States)

    Expósito Vizcaíno, S; Casanova-Mollà, J; Escoda, L; Galán, S; Miró, J

    The neuropathic pain is the most habitual problem in the neuropathy induced by chemotherapy (NIQ) and the one that more interferes in the quality of life of the patients. His precocious detection turns out to be fundamental to reduce or to eliminate the problems that from this one stem. The aims of this study were: 1) determine the incident and NIQ's characteristics and neuropathic pain in patients with mieloma multiple (MM) treated with bortezomib, and 2) to evaluate the impact of the neuropathic pain in the activities of the daily life (AVD). All the patients diagnosed of MM candidates for treatment with bortezomib attended in the Hospital Joan XXIII during 2013, took part. The participants were interviewed individually and were reporting on the presence, the characteristics and the impact of the pain, as well as of the adverse effects of the bortezomib. There took part 22 persons, of which NIQ presented the half, being the degree 2 the predominant one. The most habitual location of the neuropathic pain was hands and feet; it was appearing in a spontaneous and progressive way deteriorating in rest and during the night, with predominance of positive symptoms. The impact of the pain was reflected in all the AVD. The principal limitation was the disability to enjoy the life. The peripheral neuropathy occupied the first place in order of subjective importance for the patient followed by the fatigue and the constipation. A proper assessment and early detection of neuropathic pain is critical to minimizing its impact on the quality of life of patients. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Rapid improvement in renal function in patients with multiple myeloma and renal failure treated with bortezomib

    Directory of Open Access Journals (Sweden)

    Qayum Abdul

    2010-01-01

    Full Text Available Multiple Myeloma (MM frequently presents with renal dysfunction apart from other manifestations. Development of renal failure in patients with MM carries a poor prognosis. Bortezo-mib is a new addition to drugs used in MM and has shown good efficacy and safety profiles. Previous trials have shown its efficacy in relapsed and refractory MM as well. Studies have also shown that bortezomib is also effective in patients with MM who present with renal failure. We report here six cases of renal failure secondary to MM treated with bortezomib. All patients had poor performance status of 3-4 on ECOG scale. Five out of six patients showed satisfactory anti-myeloma response to bortezomib. Reversal of renal failure was observed in all six patients. Adverse effects to bortezomib were mild and manageable. Reversal of renal failure persisted despite incomplete response to MM in two cases, and progression of disease in one patient. It appears that bortezomib may have an effect on the kidneys in reversal of renal failure, other than its anti-myeloma effect. In conclusion, borte-zomib appears to be an effective treatment for patients with advanced MM and renal failure irres-pective of performance status and age.

  4. Protective role of humanin on bortezomib-induced bone growth impairment in anticancer treatment.

    Science.gov (United States)

    Eriksson, Emma; Wickström, Malin; Perup, Lova Segerström; Johnsen, John I; Eksborg, Staffan; Kogner, Per; Sävendahl, Lars

    2014-03-01

    Bortezomib is a proteasome inhibitor currently studied in clinical trials of childhood cancers. So far, no side effects on bone growth have been reported in treated children. However, bortezomib was recently found to induce apoptosis in growth plate chondrocytes and impair linear bone growth in treated mice. We hypothesize that [Gly(14)]-humanin (HNG), a 24-amino acid synthetic antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment. Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13 animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8 mg/kg or 1.0mg/kg), or HNG (1 µg/mouse), or the combination of HNG/bortezomib, or vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell lines, and immunohistochemistry for detection of proapoptotic proteins were also used. Statistical significance was evaluated by two-sided Mann-Whitney U test or by parametric or nonparametric analysis of variance. Bortezomib efficiently blocked the proteasome and induced pronounced impairment of linear bone growth from day 0 to day 13 (0.09 mm/day, 95% confidence interval [CI] = 0.07 to 0.11 mm/day; vs 0.19 mm/day, 95% CI = 0.15 to 0.23 mm/day in vehicle; P < .001), an effect significantly prevented by the addition of HNG (0.15 mm growth/day, 95% CI = 0.14 to 0.16 mm/day; P < .001 vs bortezomib only; P = 0.03 vs vehicle). Bortezomib was highly toxic when added to cultures of human growth plate cartilage, with markedly increased apoptosis compared with control (P < .001). However, when combining with HNG, bortezomib-induced apoptosis was entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor growth, and HNG did not interfere with the anticancer effect when studied in human tumor xenografts or cell lines. HNG prevents bortezomib-induced bone growth impairment without interfering with bortezomib's desired anticancer effects.

  5. A Case of Disseminated and Fulminant Plasmacytomas That Developed during Bortezomib Treatment

    Directory of Open Access Journals (Sweden)

    Soo-Young Bae

    2011-02-01

    Full Text Available Multiple myeloma is an incurable and slow growing plasma cell neoplasm. The introduction of new drugs has increased the number of treatment options. Bortezomib, the first-in-class proteasome inhibitor, has been shown to have a significant antitumor activity in the treatment of relapse/refractory patients with multiple myeloma. Additionally, plasmacytomas have shown significant response to bortezomib. In this case report, we describe a patient who developed disseminated and fulminant extramedullary plasmacytomas during combination chemotherapy treatment with bortezomib within a short period, after having shown clinical improvement.

  6. Linking international trademark databases to inform IP research and policy

    Energy Technology Data Exchange (ETDEWEB)

    Petrie, P.

    2016-07-01

    Researchers and policy makers are concerned with many international issues regarding trademarks, such as trademark squatting, cluttering, and dilution. Trademark application data can provide an evidence base to inform government policy regarding these issues, and can also produce quantitative insights into economic trends and brand dynamics. Currently, national trademark databases can provide insight into economic and brand dynamics at the national level, but gaining such insight at an international level is more difficult due to a lack of internationally linked trademark data. We are in the process of building a harmonised international trademark database (the “Patstat of trademarks”), in which equivalent trademarks have been identified across national offices. We have developed a pilot database that incorporates 6.4 million U.S., 1.3 million Australian, and 0.5 million New Zealand trademark applications, spanning over 100 years. The database will be extended to incorporate trademark data from other participating intellectual property (IP) offices as they join the project. Confirmed partners include the United Kingdom, WIPO, and OHIM. We will continue to expand the scope of the project, and intend to include many more IP offices from around the world. In addition to building the pilot database, we have developed a linking algorithm that identifies equivalent trademarks (TMs) across the three jurisdictions. The algorithm can currently be applied to all applications that contain TM text; i.e. around 96% of all applications. In its current state, the algorithm successfully identifies ~ 97% of equivalent TMs that are known to be linked a priori, as they have shared international registration number through the Madrid protocol. When complete, the internationally linked trademark database will be a valuable resource for researchers and policy-makers in fields such as econometrics, intellectual property rights, and brand policy. (Author)

  7. A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.

    Science.gov (United States)

    Ogawa, Yoshiaki; Ogura, Michinori; Tobinai, Kensei; Ando, Kiyoshi; Suzuki, Tatsuya; Watanabe, Takashi; Ohmachi, Ken; Uchida, Toshiki; Hanson, Mary E; Tanaka, Yoshinobu; Koh, Yasuhiro; Shimamoto, Takashi; Hotta, Tomomitsu

    2016-01-01

    This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.3 mg/m(2) intravenous bortezomib (Days 1, 4, 8, and 11) and oral vorinostat 400 mg (Days 1 through 14) and were further evaluated. Vorinostat and bortezomib treatment doses were determined by DLT and safety, tolerability, and treatment response were assessed. Of 7 enrolled patients, 6 were evaluated, and one developed DLTs. The most common adverse events were leukopenia, neutropenia, thrombocytopenia, diarrhea, nausea, decreased appetite, and vomiting. Combination of vorinostat plus bortezomib did not increase vorinostat exposure at Day 11 [AUC0-24 h ratio (95% CI) = 1.08 (0.80, 1.45)]; geometric mean AUC0-24 h ratio for bortezomib (90% CI) was 1.96 (1.24-3.12). Objective therapeutic response occurred in 3 patients, including 1 complete response and 2 partial responses. Vorinostat 400 mg plus bortezomib 1.3 mg/m(2) was safe and well-tolerated in Japanese patients with relapsed or refractory MM not considered bortezomib refractory (NCT00858234).

  8. GammaCam trademark radiation imaging system

    International Nuclear Information System (INIS)

    1998-02-01

    GammaCam trademark, a gamma-ray imaging system manufactured by AIL System, Inc., would benefit a site that needs to locate radiation sources. It is capable of producing a two-dimensional image of a radiation field superimposed on a black and white visual image. Because the system can be positioned outside the radiologically controlled area, the radiation exposure to personnel is significantly reduced and extensive shielding is not required. This report covers the following topics: technology description; performance; technology applicability and alternatives; cost; regulatory and policy issues; and lessons learned. The demonstration of GammaCam trademark in December 1996 was part of the Large-Scale Demonstration Project (LSDP) whose objective is to select and demonstrate potentially beneficial technologies at the Argonne National Laboratory-East (ANL) Chicago Pile-5 Research Reactor (CP-5). The purpose of the LSDP is to demonstrate that by using innovative and improved decontamination and decommissioning (D and D) technologies from various sources, significant benefits can be achieved when compared to baseline D and D technologies

  9. SPEEDUP{trademark} ion exchange column model

    Energy Technology Data Exchange (ETDEWEB)

    Hang, T.

    2000-03-06

    A transient model to describe the process of loading a solute onto the granular fixed bed in an ion exchange (IX) column has been developed using the SpeedUp{trademark} software package. SpeedUp offers the advantage of smooth integration into other existing SpeedUp flowsheet models. The mathematical algorithm of a porous particle diffusion model was adopted to account for convection, axial dispersion, film mass transfer, and pore diffusion. The method of orthogonal collocation on finite elements was employed to solve the governing transport equations. The model allows the use of a non-linear Langmuir isotherm based on an effective binary ionic exchange process. The SpeedUp column model was tested by comparing to the analytical solutions of three transport problems from the ion exchange literature. In addition, a sample calculation of a train of three crystalline silicotitanate (CST) IX columns in series was made using both the SpeedUp model and Purdue University's VERSE-LC code. All test cases showed excellent agreement between the SpeedUp model results and the test data. The model can be readily used for SuperLig{trademark} ion exchange resins, once the experimental data are complete.

  10. Trademark Trends and Brand Activity in Higher Education

    Science.gov (United States)

    Rooksby, Jacob H.; Collins, Christopher S.

    2016-01-01

    Trademarks figure prominently in college and university brand formation efforts. Trademarks are intangible rights that allow institutions to define and protect aspects of their identities important to them as they engage in markets. This multiple-method study, grounded in legal and policy research, provides a first look at how institutions are…

  11. Trademark use doctrine in the European Union and Japan

    NARCIS (Netherlands)

    Husovec, Martin

    2016-01-01

    The scope of the regulatory power of trademark law in the market-place is constantly being tested against the new developments in technology. Today, the rights arising from the trademarks increasingly cover large portion of activities going beyond the mere misrepresentation of goods and services.

  12. Comment: Convergence of Trademark Law and E-Commerce ...

    African Journals Online (AJOL)

    Comment: Convergence of Trademark Law and E-Commerce: Overview of US, EU and China Regulations on Trademarks and Domain Names. ... also highlights the importance of intellectual property rights for economic development. Key words: Industrial property, cybersquatting, internet domain names, metatags ...

  13. BWR spent fuel transport and storage system for KKL: TN trademark 52L, TN trademark 97L, TN trademark 24 BHL

    International Nuclear Information System (INIS)

    Sicard, D.; Verdier, A.; Monsigny, P.A.

    2004-01-01

    The LEIBSTADT (KKL) nuclear power plant in Switzerland has opted to ship spent fuel to a central facility called ZWILAG for interim storage. In the mid-nineties, COGEMA LOGISTICS was contracted by KKL for the supply of the TN trademark a52L and TN trademark 97L transport and storage casks for BWR fuel types. In 2003, KKL also ordered from COGEMA LOGISTICS the supply of six TNae24 BHL transport and storage casks. This paper shows how all the three cask designs have responded to the KKL needs to ship and store BWR spent fuel. In addition, it highlights the already significant operational feedback of the TN trademark 52L and TN trademark 97L casks by the KKL and ZWILAG operators

  14. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  15. Bortezomib partially protects the rat diaphragm from ventilator-induced diaphragm dysfunction

    NARCIS (Netherlands)

    Agten, A.; Maes, K.; Thomas, D; Cielen, N.; Hees, H.W. van; Dekhuijzen, R.; Decramer, M.; Gayan-Ramirez, G.

    2012-01-01

    OBJECTIVE: Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, bortezomib, would have a protective

  16. Pulse treatment with the proteasome inhibitor bortezomib inhibits osteoclast resorptive activity in clinically relevant conditions

    DEFF Research Database (Denmark)

    Boissy, P; Levin Andersen, Thomas; Lund, T

    2008-01-01

    Myeloma bone disease is due to bone degradation by osteoclasts, and absence of repair by bone forming osteoblasts. Recent observations suggest that the anti-myeloma drug bortezomib, a proteasome inhibitor, stimulates bone formation and may inhibit bone resorption. Here, we tested bortezomib...... on cultured osteoclasts in conditions mimicking the pulse treatment used in the clinic, thereby avoiding continuous proteasome inhibition and unselective toxicity. A 3h pulse with 25nM bortezomib followed by a 3-day culture in its absence markedly inhibited osteoclast activity as evaluated through bone...... cells drastically reduced their survival. We measured next the levels of two bone resorption markers in patients during the 3 days following five and seven therapeutic bortezomib administrations, respectively. These levels decreased significantly already 1-2 days after injection, and then increased...

  17. SNRB{trademark} air toxics monitoring. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    Babcock & Wilcox (B&W) is currently conducting a project under the DOE`s Clean Coal Technology (CCT II) Program to demonstrate its SO{sub x}NO{sub x}-Rox Box{trademark} (SNRB{trademark}) process in a 5 MWe Field Demonstration Unit at Ohio Edison`s R. E. Burger Plant near Shadyside, Ohio. The objective of the SNRB{trademark} Air Toxics Monitoring Project was to provide data on SNRB{trademark} air toxics emissions control performance to B&W and to add to the DOE/EPRI/EPA data base by quantifying the flow rates of selected hazardous substances (or air toxics) in all of the major input and output streams of the SNRB{trademark} process as well as the power plant. Work under the project included the collection and analysis of representative samples of all major input and output streams of the SNRB{trademark} demonstration unit and the power plant, and the subsequent laboratory analysis of these samples to determine the partitioning of the hazardous substances between the various process streams. Material balances for selected air toxics were subsequently calculated around the SNRB{trademark} and host boiler systems, including the removal efficiencies across each of the major air pollution control devices. This report presents results of the SNRB{trademark} Air Toxics Monitoring Project. In addition to the Introduction, a brief description of the test site, including the Boiler No. 8 and the SNRB{trademark} process, is included in Section H. The concentrations of air toxic emissions are presented in Section II according to compound class. Material balances are included in Section IV for three major systems: boiler, electrostatic precipitator, and SNRB{trademark}. Emission factors and removal efficiencies are also presented according to compound class in Sections V and VI, respectively. A data evaluation is provided in Section VII.

  18. BWR-spent fuel transport and storage with the TN trademark 9/4 and TN trademark 24BH casks

    International Nuclear Information System (INIS)

    Wattez, L.; Marguerat, Y.; Hoesli, C.

    2004-01-01

    The Swiss Nuclear Utilities have started in 2001 to store spent fuel in dry metallic dual-purpose casks in ZWILAG, the Swiss interim storage facility. BKW FMB Energy Ltd., as Muehleberg Nuclear Power Plant owner, is involved in this process and has selected to store its spent fuel, a new high capacity dual-purpose cask, the TN trademark 24BH. For the transport in a medium size cask, COGEMA LOGISTICS has developed a new cask, the TN trademark 9/4, to replace the NTL9 cask, which performed numerous transports of BWR spent fuel in the past decades. Licensed IAEA 1996, the TN trademark 9/4 is a 40 ton transport cask, for 7 BWR high burn-up spent fuel assemblies. The spent fuel assemblies can be transferred in the ZWILAG hot cell in the TN trademark 24BH cask. The first use of these casks took place in 2003. Ten TN trademark 9/4 transports were performed, and one TN trademark 24BH was loaded. After a brief presentation of the operational aspects, the paper will focus on the TN trademark 24BH high capacity dual purpose cask, the TN trademark 9/4 transport cask and describe in detail their characteristics and possibilities

  19. Effects of the proteasome inhibitor, bortezomib, on cytodifferentiation and mineralization of periodontal ligament cells.

    Science.gov (United States)

    Kitagaki, J; Miyauchi, S; Xie, C J; Yamashita, M; Yamada, S; Kitamura, M; Murakami, S

    2015-04-01

    The proteasome inhibitor, bortezomib, is known to induce osteoblastic differentiation in a number of cell lines, such as mesenchymal stem cells and osteoblastic precursor cells. As periodontal ligament (PDL) cells are multipotent, we examined whether bortezomib may induce the differentiation of PDL cells into hard-tissue-forming cells. A mouse PDL clone cell line, MPDL22 cells, was cultured in mineralization medium in the presence or absence of bortezomib. Expression of calcification-related genes and calcified-nodule formation were evaluated by real-time PCR and Alizarin Red staining, respectively. Bortezomib increased the expression of calcification-related mRNAs, such as tissue nonspecific alkaline phosphatase isoenzyme (ALPase), bone sialoprotein (Bsp), runt-related transcription factor 2 (Runx2) and osteopontin, and calcified-nodule formation in MPDL22 cells. These effects were induced, in part, by increasing the cytosolic accumulation and nuclear translocation of β-catenin, leading to an increase in expression of bone morphogenetic protein (Bmp)-2, -4 and -6 mRNAs. In addition, bortezomib enhanced BMP-2-induced expression of Bsp and osteopontin mRNAs and increased calcified-nodule formation in MPDL22 cells. Bortezomib induced cytodifferentiation and mineralization of PDL cells by enhancing the accumulation of β-catenin within the cytosol and the nucleus and increasing the expression of Bmp-2, -4 and -6 mRNAs. Moreover, bortezomib enhanced the BMP-2-induced cytodifferentiation and mineralization of PDL cells, suggesting that bortezomib may be efficacious for use in periodontal regeneration therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Visualizing the antivascular effect of bortezomib on the hypoxic tumor microenvironment.

    Science.gov (United States)

    Sun, Xiaorong; Ackerstaff, Ellen; He, Fuqiu; Xing, Ligang; Hsiao, Hung Tsung; Koutcher, Jason A; Ling, C Clifton; Li, Gloria C

    2015-10-27

    Bortezomib, a novel proteasome inhibitor, has been approved for treating multiple myeloma and mantle cell lymphoma and studied pre-clinically and clinically for solid tumors. Preferential cytotoxicity of bortezomib was found toward hypoxic tumor cells and endothelial cells in vitro. The purpose of this study is to investigate the role of a pretreatment hypoxic tumor microenvironment on the effects of bortezomib in vitro and ex vivo, and explore the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to noninvasively evaluate the biological effects of bortezomib. It was shown in vitro by Western blot, flow cytometry, and ELISA that bortezomib accumulated HIF-1α in non-functional forms and blocks its hypoxia response in human colorectal cancer cell lines. Ex vivo experiments were performed with fluorescent immunohistochemical staining techniques using multiple endogenous and exogenous markers to identify hypoxia (pimonidazole, HRE-TKeGFP), blood flow/permeability (Hoechst 33342), micro-vessels (CD31 and SMA), apoptosis (cleaved caspase 3) and hypoxia response (CA9). After bortezomib administration, overall apoptosis index was significantly increased and blood perfusion was dramatically decreased in tumor xenografts. More importantly, apoptosis signals were found preferentially located in moderate and severe pretreatment hypoxic regions in both tumor and endothelial cells. Meanwhile, DCE MRI examinations showed that the tumor blood flow and permeability decreased significantly after bortezomib administration. The present study revealed that bortezomib reduces tumor hypoxia response and blood perfusion, thus, presenting antivascular properties. It will be important to determine the hypoxic/perfusion status pre- and during treatment at further translational studies.

  1. Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kahl Brad S

    2008-05-01

    Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

  2. The effect of Bortezomib and Rapamycin on Telomerase Activity in Mantle Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Orit Uziel

    2014-12-01

    In the light of the crucial role of telomerase in cancer cells, it was important to characterize the possible relations between telomerase and bortezomib and to distinguish the biochemical mechanisms of its regulation and its interactions with other signal transduction inhibitors such as rapamycin. The results of this work encourage the in vivo examination of the therapeutic potential of the combination of bortezomib and rapamycin in Mantle Cell Lymphoma patients.

  3. Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma

    DEFF Research Database (Denmark)

    Hjorth, Martin; Hjertner, Øyvind; Knudsen, Lene Meldgaard

    2012-01-01

    Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives.......Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives....

  4. A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.

    Science.gov (United States)

    Schelman, William R; Traynor, Anne M; Holen, Kyle D; Kolesar, Jill M; Attia, Steven; Hoang, Tien; Eickhoff, Jens; Jiang, Zhisheng; Alberti, Dona; Marnocha, Rebecca; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H

    2013-12-01

    A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%), anorexia (30.4%) and constipation (26.1%). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.

  5. Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

    Directory of Open Access Journals (Sweden)

    Shota Yamamoto

    2015-09-01

    Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

  6. BAK and NOXA are critical determinants of mitochondrial apoptosis induced by bortezomib in mesothelioma.

    Directory of Open Access Journals (Sweden)

    Sara Busacca

    Full Text Available Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM, two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05-10. However, the potential mechanisms underlying resistance to this targeted drug in MPM are still unknown. Functional genetic analyses were conducted to determine the key mitochondrial apoptotic regulators required for bortezomib sensitivity and to establish how their dysregulation may confer resistance. The multidomain proapoptotic protein BAK, but not its orthologue BAX, was found to be essential for bortezomib-induced apoptosis in MPM cell lines. Immunohistochemistry was performed on tissues from the ICORG-05 phase II trial and a TMA of archived mesotheliomas. Loss of BAK was found in 39% of specimens and loss of both BAX/BAK in 37% of samples. However, MPM tissues from patients who failed to respond to bortezomib and MPM cell lines selected for resistance to bortezomib conserved BAK expression. In contrast, c-Myc dependent transactivation of NOXA was abrogated in the resistant cell lines. In summary, the block of mitochondrial apoptosis is a limiting factor for achieving efficacy of bortezomib in MPM, and the observed loss of BAK expression or NOXA transactivation may be relevant mechanisms of resistance in the clinic.

  7. Results of the first bortezomib-based induction therapy in the treatment of multiple myeloma.

    Science.gov (United States)

    Kortüm, Martin; Einsele, Hermann

    2011-07-01

    This is a comment on the IFM 2005-01 Phase III trial that compared, for the first time, the efficacy and the safety of a bortezomib-containing induction regimen with conventional chemotherapy before autologous stem-cell transplantation in multiple myeloma (MM) patients. Between 2005 and 2008, 482 patients were randomized to vincristin/doxorubicin/dexamethasone (VAD), VAD + dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) consolidation, bortezomib + dexamethasone and bortezomib + dexamethasone + DCEP consolidation followed by autologous stem-cell transplantation. The trial was conducted in 89 sites in France, Belgium and Switzerland. The novel agent-based induction therapy (bortezomib/dexamethasone) achieved higher complete remission (CR)/nearCR rates, as well as less treatment-related mortality, but higher rates of polyneuropathy than the conventional chemotherapy-based induction therapy (VAD/VAD + DCEP). The difference in progression-free survival (PFS) difference was not statistically significant but a trend to longer PFS was seen to favor to the bortezomib-containing regimen; bortezomib and dexamethason (BD) was, therefore, proposed to be a standard of care by the authors of the study. © 2011 Informa UK, Ltd.

  8. Update on treatment of follicular non-Hodgkin’s lymphoma: focus on potential of bortezomib

    Directory of Open Access Journals (Sweden)

    Brander DM

    2012-03-01

    Full Text Available Danielle M Brander, Anne W BeavenDuke University Medical Center, Durham, NC, USAAbstract: Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade®, a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies. Several clinical trials were conducted with bortezomib for the treatment of non-Hodgkin’s lymphoma. As a single agent, overall responses in follicular lymphoma varied greatly (16%–41%, with weekly bortezomib showing less neurotoxicity than twice-weekly regimens, but with concern about decreased responses. Combination with rituximab was projected to improve the efficacy of bortezomib, but this resulted in increased toxicities and questionable added benefit. Although the largest Phase III study in follicular lymphoma of bortezomib plus rituximab versus rituximab alone demonstrated a significant progression-free survival difference, the absolute difference was small (12.8 months versus 11 months. Combining bortezomib with established regimens, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP, or rituximab-bendamustine also did not show definite benefit, and many of these studies did not meet their primary endpoint when bortezomib failed to improve responses or survival to the degree anticipated. In a disease where the goal of treatment is palliative and affected patients often have other medical and treatment-related comorbidities, decisions regarding therapies

  9. The relevance of introducing opposition proceedings into the Serbian trademark legislation

    Directory of Open Access Journals (Sweden)

    Vasić Aleksandra

    2014-01-01

    Full Text Available This paper analyzes the quality of certain legal procedures applied in domestic trademark legislation in the light of harmonizing our legislation with those of the EU. Trademark Law in the Republic of Serbia (2009 does not rely on opposition proceedings as a phase in the process of trademark registration and a tool that would ensure that only those trademarks that fulfill the necessary conditions are granted legal protection. Intellectual Property Office examines the so-called relative grounds for trademark registration refusal but does so ex officio, thus preventing the holders of trademark rights from benefiting from a relatively inexpensive and effective opposition procedure regarding the registration of a second trademark which violates their previously established rights. In contrast to our trademark laws, EU Council Regulation 207/2009 on Community Trademarks of February 26, 2009 (CTMR -Community trademark regulation enforces opposition proceedings as the most important phase in the process of trademark registration. European experience shows that opposition proceedings carry significant benefits for the process of trademark application. First of all, they allow the holders of previously established trademark rights to avoid long and costly court proceedings whose purpose is to dispute trademarks that violate the owner's rights. Also, state agencies authorizing in trademark approval no longer need to monitor registered trademarks.

  10. Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.

    Science.gov (United States)

    Wei, Jia-You; Liu, Cui-Cui; Ouyang, Han-Dong; Ma, Chao; Xie, Man-Xiu; Liu, Meng; Lei, Wan-Long; Ding, Huan-Huan; Wu, Shao-Ling; Xin, Wen-Jun

    2017-10-01

    Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment. In addition, inhibition of STAT3 activity by S3I-201 attenuated bortezomib-induced mechanical allodynia and central sensitization. Local knockdown of STAT3 also ameliorated the mechanical allodynia induced by bortezomib administration. Our results suggest that accumulation of methylglyoxal may activate the RAGE/STAT3 signaling pathway in dorsal horn, and contributes to the spinal central sensitization and persistent pain induced by bortezomib treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Bortezomib-based treatment of acute antibody-mediated rejection: a case report.

    Science.gov (United States)

    Wang, Q; Li, X L; Xu, X G; Shi, B Y; Zhang, Z M; Li, Z L; Han, Y; Zhou, W Q; Chen, C Q; Cai, M; Zhang, X

    2015-12-22

    Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

  12. Comparison of MultiHance {sup trademark} and Gadovist {sup trademark} for cerebral MR perfusion imaging in healthy volunteers; Vergleich von MultiHance {sup trademark} und Gadovist {sup trademark} zur zerebralen MR-Perfusionsmessung bei gesunden Probanden

    Energy Technology Data Exchange (ETDEWEB)

    Essig, M.; LeHuu, M.; Huebener, M.; Kaick, G. van [Deutsches Krebsforschungszentrum, Abt. Radiologische Diagnostik und Therapie, Heidelberg (Germany); Lodemann, K.P. [Bracco-Byk, Gulden (Germany); Schoenberg, S.O. [Institut fuer Klinische Radiologie, Ludwig-Maximilians-Universitaet Muenchen, Grosshadern (Germany)

    2002-11-01

    To evaluate the weakly protein interacting MR contrast agent MultiHance {sup trademark} and the one-molar agent Gadovist {sup trademark} for cerebral perfusion MR imaging, a randomized intraindividual study was conducted in 12 healthy male volunteers. Perfusion-MRI was performed with single and double dose of each contrast agent on a 1.5T MR system using a gradient-echo EPI sequence. The imaging parameters, slice positioning and contrast media application were standardized. For the quantitative assessment rCBV and rCBF measurements of gray and white matter were performed. Additionally, the percentage of signal drop and the full width half maximum (FWHM) of ROI signal time curves were quantified. In a qualitative analysis the image quality of the rCBV and rCBF maps were assessed.Single dosage of the used new contrast agents was sufficient to achieve high quality perfusion maps. The susceptibility effect, described by percentage of signal loss (Gadovist {sup trademark} : 29.4% vs. MultiHance {sup trademark} : 28.3%) and the FWHM (Gadovist {sup trademark} : 6.4 s vs. Multihance {sup trademark} : 7.0 s) were not different between the agents for single dose.The one molar MR contrast agent Gadovist {sup trademark} has no advantages over MultiHance {sup trademark}, a MR contrast agent with a higher relaxivity in perfusion MRI. Both agents allow the calculation of high quality perfusion maps at a dosage of 0.1 mmol/kg bw with physiologic absolute values for regional CBV and CBF. The susceptibility effect is comparable for both agents and stronger than with conventional MR contrast media. (orig.) [German] Zur Evaluierung des gering proteinbindenden MR-Kontrastmittels MultiHance {sup trademark} und des einmolaren MR-Kontrastmittels Gadovist {sup trademark} fuer die MR-Perfusionsmessung im Gehirn wurden in einer randomisierten, intraindividuellen Vergleichsstudie 12 gesunde maennliche Probanden untersucht. Die Perfusionsmessung wurde an einem 1,5-T-MRT mit einer T2

  13. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT

    DEFF Research Database (Denmark)

    Gimsing, P; Hjertner, Ø; Abildgaard, N

    2015-01-01

    Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...

  14. ALARA{trademark} 1146 strippable coating

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, V.

    1999-12-17

    Strippable or temporary coatings are innovative technologies for decontamination that effectively reduce loose contamination at low cost. These coatings have become a viable option during the deactivation and decommissioning of both US Department of Energy (DOE) and commercial nuclear facilities to remove or fix loose contamination on both vertical and horizontal surfaces. The ALARA{trademark} 1146 strippable coating was demonstrated as part of the Savannah River Site LSDDP and successfully removed transferable (surface) contamination from multiple surfaces (metal and concrete) with an average decontamination factor for alpha contamination of 6.68 and an average percentage of alpha contamination removed of 85.0%. Beta contamination removed was an average DF of 5.55 and an average percentage removed of 82.0%. This paper is an Innovative Technology Summary Report designed to provide potential users with the information they need to quickly determine if a technology would apply to a particular environmental management problem. They also are designed for readers who may recommend that a technology be considered by prospective users. This Innovative Technology offers a 35% cost savings over the Baseline Technology.

  15. Industrial ecology Prosperity Game{trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Beck, D.; Boyack, K.; Berman, M.

    1998-03-01

    Industrial ecology (IE) is an emerging scientific field that views industrial activities and the environment as an interactive whole. The IE approach simultaneously optimizes activities with respect to cost, performance, and environmental impact. Industrial Ecology provides a dynamic systems-based framework that enables management of human activity on a sustainable basis by: minimizing energy and materials usage; insuring acceptable quality of life for people; minimizing the ecological impact of human activity to levels that natural systems can sustain; and maintaining the economic viability of systems for industry, trade and commerce. Industrial ecology applies systems science to industrial systems, defining the system boundary to incorporate the natural world. Its overall goal is to optimize industrial activities within the constraints imposed by ecological viability, globally and locally. In this context, Industrial systems applies not just to private sector manufacturing and services but also to government operations, including provision of infrastructure. Sandia conducted its seventeenth Prosperity Game{trademark} on May 23--25, 1997, at the Hyatt Dulles Hotel in Herndon, Virginia. The primary sponsors of the event were Sandia National Laboratories and Los Alamos National Laboratory, who were interested in using the format of a Prosperity Game to address some of the issues surrounding Industrial Ecology. Honorary game sponsors were: The National Science Foundation; the Committee on Environmental Improvement, American Chemical Society; the Industrial and Engineering Chemistry Division, American Chemical Society; the US EPA--The Smart Growth Network, Office of Policy Development; and the US DOE-Center of Excellence for Sustainable Development.

  16. Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice

    NARCIS (Netherlands)

    Wu, KL; van Wieringen, W; Vellenga, E; Zweegman, S; Lokhorst, HM; Sonneveld, P

    The clinical data on the efficacy and toxicity of bortezomib as treatment for multiple myeloma patients are restricted to prospective phase II studies in expert myeloma centers. Here we report a multi-institutional analysis of the efficacy and toxicity of bortezomib in patients with relapsed or

  17. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer

    NARCIS (Netherlands)

    de Wilt, Leonie H. A. M.; Jansen, Gerrit; Assaraf, Yehuda G.; van Meerloo, Johan; Cloos, Jacqueline; Schimmer, Aaron D.; Chan, Elena T.; Kirk, Christopher J.; Peters, Godefridus J.; Kruyt, Frank A. E.

    2012-01-01

    The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC). Here we studied the proteasome-based mechanisms underlying intrinsic and acquired bortezomib resistance in NSCLC cells.

  18. Proteasome Inhibitor Bortezomib Suppresses Nuclear Factor-Kappa B Activation and Ameliorates Eye Inflammation in Experimental Autoimmune Uveitis

    Directory of Open Access Journals (Sweden)

    Sheng-Min Hsu

    2015-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used for hematologic cancer treatment. Since it can suppress NF-κB activation, which is critical for the inflammatory process, bortezomib has been found to possess anti-inflammatory activity. In this study, we evaluated the effect of bortezomib on experimental autoimmune uveitis (EAU in mice and investigated the potential mechanisms related to NF-κB inactivation. High-dose bortezomib (0.75 mg/kg, low-dose bortezomib (0.15 mg/kg, or phosphate buffered saline was given after EAU induction. We found that the EAU is ameliorated by high-dose bortezomib treatment when compared with low-dose bortezomib or PBS treatment. The DNA-binding activity of NF-κB was suppressed and expression of several key inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-12, IL-17, and MCP-1 was lowered in the high-dose bortezomib-treated group. These results suggest that proteasome inhibition is a promising treatment strategy for autoimmune uveitis.

  19. The Positive Effects of One-Hour Intravenous Administration of Bortezomib on Peripheral Neuropathy in Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Joo Young Jung

    2014-01-01

    Full Text Available Bortezomib-induced peripheral neuropathy (BiPN in multiple myeloma (MM patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males. The median number of treatment cycles was 5 (range 2–10. The cumulative bortezomib dose was 26.0 mg/m2 (14.3–66.3 and percent of actual per expected cumulative dose was 90% (50–100. The overall response (complete response plus partial response rate was 65%. The incidence of BiPN was 57% (n = 13 and incidence of severe neuropathy was 4% (n = 1. One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration.

  20. Bortezomib in plasmablastic lymphoma: A glimpse of hope for a hard-to-treat disease.

    Science.gov (United States)

    Guerrero-Garcia, Thomas A; Mogollon, Renzo J; Castillo, Jorge J

    2017-11-01

    Plasmablastic lymphoma (PBL) is a rare and hard to treat disease. With current standard chemotherapeutic regimens, PBL is associated with a median overall survival of 12-15 months. We performed a systematic review of the literature through March 31, 2017 looking for patients with a diagnosis of PBL who were treated with bortezomib, alone or in combination. We identified 21 patients, of which 11 received bortezomib in the frontline setting and 10 received bortezomib in the relapsed setting. Eleven patients were HIV-positive and 10 were HIV-negative. The overall response rate to bortezomib-containing regimens was 100% in the frontline setting and 90% in the relapsed setting. Furthermore, the 2-year overall survival of patients treated upfront was 55%, and the median OS in relapsed patients was 14 months. Although the sample size is small, we believe our results are encouraging and should serve as rationale to investigate bortezomib-based regimens in patients with PBL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Phase 1 Study of Sorafenib in Combination with Bortezomib in Patients with Advanced Malignancies

    Science.gov (United States)

    Kumar, Shaji K.; Jett, James; Marks, Randolph; Richardson, Ronald; Quevedo, Fernando; Moynihan, Timothy; Croghan, Gary; Markovic, Svetomir N.; Bible, Keith C.; Qin, Rui; Tan, Angelina; Molina, Julian; Kaufmann, Scott H.; Erlichman, Charles; Adjei, Alex A.

    2013-01-01

    Background Sorafenib (a VEGFR and multi-targeted kinase inhibitor) and Bortezomib (a proteasome inhibitor) have clinical antineoplastic activities as single agents, and combine synergistically in preclinical models. Methods This Phase I study was undertaken to define the toxicity and the maximum tolerated doses (MTD) of the combination in patients with advanced solid tumors. Patients with cytologic or histologic proof of unresectable solid tumors were treated with escalating doses of sorafenib (twice daily) and bortezomib (days 1, 4, 8 and 11 intravenously) with 21-day cycles. Results Fourteen patients (7 males, median age 65, range 24–74), with renal (3), lung (3), pancreas (2), and breast, adrenal gland, melanoma, spindle cell tumor, chronic lymphocytic leukemia and multiple myeloma (1 each) were enrolled. All patients are off treatment, 10 due to disease progression. DLT was seen in two patients (one grade 3 abdominal pain and grade 4 lipase elevation; one with grade 3 vomiting) at sorafenib 200 mg twice daily and bortezomib 1.3 mg/m2, establishing the MTD. No grade 4 hematologic or grade 5 toxicities were seen. One patient with renal cell cancer had a partial response and 5 patients attained stable disease. Conclusions The combination of sorafenib and bortezomib was tolerated well. The recommended phase 2 doses are sorafenib 200 mg twice daily continuously with bortezomib 1 mg/m2 on days 1, 4, 8, 11 (21 day cycles). The combination shows preliminary signs of efficacy, supporting phase 2 studies. PMID:23887852

  2. The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib

    Directory of Open Access Journals (Sweden)

    A Milano

    2009-06-01

    Full Text Available A Milano,1 F Perri,2 F Caponigro21Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy; 2Head and Neck Medical Oncology Unit, National Tumour institute of Naples, Naples, ItalyAbstract: The ubiquitin–proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341 is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-κB and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors. Keywords: proteasome, bortezomib, NF-κB, clinical studies, solid tumors

  3. Treatment with bortezomib in multiple myeloma is associated with only a transient and brief increase of bone specific alkaline phosphatase

    DEFF Research Database (Denmark)

    Haidl, Felix; Plesner, Torben; Lund, Thomas

    2012-01-01

    There are indications of a bone anabolic effect associated with bortezomib treatment. We present a study with long follow up, measuring bone specific alkaline phosphatase (bALP) for a year during and after treatment in an unselected cohort of myeloma patients treated with bortezomib, and assess...... factors of potential influence on the increase of bALP. Our main findings are that bALP increase is of short duration and declines significantly even during continued treatment with bortezomib. Only myeloma response was associated with a significant increase of bALP; whereas previous treatment...... with bortezomib, previous or concomitant treatment with zoledronic acid i.v., dose of bortezomib, line of treatment, or combination with other chemotherapy was not....

  4. The protective effects of the proteasome inhibitor bortezomib (velcade on ischemia-reperfusion injury in the rat retina.

    Directory of Open Access Journals (Sweden)

    Fang-Ting Chen

    Full Text Available PURPOSE: To evaluate the protective effects of bortezomib (Velcade on ischemia-reperfusion (IR injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg, or high-dose bortezomib (0.2 mg/kg before the induction of IR injury. Electroretinography (ERG was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α, anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin, and pro-apoptotic proteins (p53, bax were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein, NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

  5. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  6. Recurrent syncope and cardiac arrest in a patient with systemic light chain amyloidosis treated with bortezomib

    Directory of Open Access Journals (Sweden)

    Navin Jaipaul

    2016-05-01

    Full Text Available About 10-15% of patients with multiple myeloma develop light chain (AL amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation.

  7. SINGLE-FACED GRAYQB{trademark} - A RADIATION MAPPING DEVICE

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, J.; Farfan, E.; Immel, D.; Phillips, M.; Bobbitt, J.; Plummer, J.

    2013-12-12

    GrayQb{trademark} is a novel technology that has the potential to characterize radioactively contaminated areas such as hot cells, gloveboxes, small and large rooms, hallways, and waste tanks. The goal of GrayQb{trademark} is to speed the process of decontaminating these areas, which reduces worker exposures and promotes ALARA considerations. The device employs Phosphorous Storage Plate (PSP) technology as its primary detector material. PSPs, commonly used for medical applications and non-destructive testing, can be read using a commercially available scanner. The goal of GrayQb{trademark} technology is to locate, quantify, and identify the sources of contamination. The purpose of the work documented in this report was to better characterize the performance of GrayQb{trademark} in its ability to present overlay images of the PSP image and the associated visual image of the location being surveyed. The results presented in this report are overlay images identifying the location of hot spots in both controlled and field environments. The GrayQb{trademark} technology has been mainly tested in a controlled environment with known distances and source characteristics such as specific known radionuclides, dose rates, and strength. The original concept for the GrayQb{trademark} device involved utilizing the six faces of a cube configuration and was designed to be positioned in the center of a contaminated area for 3D mapping. A smaller single-faced GrayQb{trademark}, dubbed GrayQb SF, was designed for the purpose of conducting the characterization testing documented in this report. This lighter 2D version is ideal for applications where entry ports are too small for a deployment of the original GrayQb™ version or where only a single surface is of interest. The shape, size, and weight of these two designs have been carefully modeled to account for most limitations encountered in hot cells, gloveboxes, and contaminated areas. GrayQb{trademark} and GrayQb{trademark} SF

  8. Bortezomib is safe in and stabilizes pulmonary function in patients with allo-HSCT-associated pulmonary CGVHD.

    Science.gov (United States)

    Jain, Manu; Budinger, Grs; Jovanovic, Borko; Dematte, Jane; Duffey, Sara; Mehta, Jayesh

    2018-03-09

    Pulmonary chronic graft-versus-host disease (p-CGVHD) following allogeneic HSCT is devastating with limited proven treatments. Although sporadically associated with pulmonary toxicity, the proteasome inhibitor bortezomib may be efficacious in p-CGVHD. We sought to establish safety and tolerability of bortezomib in pilot, open-label trial of patients with p-CGVHD. The primary endpoint was adverse events. Efficacy was assessed by comparing FEV1 decline prior to p-CGVHD diagnosis to during the bortezomib treatment period. The impact on pulmonary function testing of prior long-term bortezomib treatment in multiple myeloma (MM) patients was also assessed as a safety analysis. Seventeen patients enrolled in the pilot study with a mean time to p-CGVHD diagnosis of 3.36 years (±1.88 years). Bortezomib was well tolerated without early dropouts. The median FEV1 decline prior to the diagnosis of p-CGVHD was -1.06%/month (-5.36, -0.33) and during treatment was -0.25%/month (-9.42, 3.52). In the safety study, there was no significant difference in any PFT parameter between 73 patients who received bortezomib and 68 patients who did not for MM. Thus, we conclude that bortezomib has acceptable safety and tolerability in patients with compromised pulmonary function. The efficacy of proteosomal inhibition should be assessed in a large trial of chronic p-CGVHD patients.

  9. A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.

    Science.gov (United States)

    Chen, Shuang; Zhang, Yu; Zhou, Liang; Leng, Yun; Lin, Hui; Kmieciak, Maciej; Pei, Xin-Yan; Jones, Richard; Orlowski, Robert Z; Dai, Yun; Grant, Steven

    2014-10-23

    Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib resistance in Bim(hi) cells, adaptive bortezomib-resistant cells displayed marked Bim downregulation. HDACI upregulated Bim and, when combined with ABT-737, which released Bim from Bcl-2/Bcl-xL, potently killed bortezomib-resistant cells. These events were correlated with Bim-associated autophagy attenuation, whereas Bim knockdown sharply increased autophagy in Bim(hi) cells. In Bim(low) cells, autophagy disruption by chloroquine (CQ) was required for HDACI/ABT-737 to induce Bim expression and lethality. CQ also further enhanced HDACI/ABT-737 lethality in bortezomib-resistant cells. Finally, HDACI failed to diminish autophagy or potentiate ABT-737-induced apoptosis in bim(-/-) mouse embryonic fibroblasts. Thus, Bim deficiency represents a novel mechanism of adaptive bortezomib resistance in MM cells, and Bim-targeting strategies combining HDACIs (which upregulate Bim) and BH3 mimetics (which unleash Bim from antiapoptotic proteins) overcomes such resistance, in part by disabling cytoprotective autophagy. © 2014 by The American Society of Hematology.

  10. Bortezomib-based vs non-bortezomib-based post-transplantation treatment in multiple myeloma patients: a systematic review and meta-analysis of Phase III randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Liu XP

    2015-06-01

    Full Text Available Xiaoping Liu,1 Colin K He,2 Xiangyu Meng,1 Li He,1 Kaili Li,1 Qing Liang,1 Liang Shao,1 Shangqin Liu1 1Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Orient Health Care, NYC, USA Objective: To evaluate the efficacy and safety of bortezomib-based vs non-bortezomib-based post-transplantation therapy in patients with multiple myeloma.Methods: Data of relevant randomized controlled trials assessing the effect of bortezomib as post-transplantation consolidation or maintenance therapy was obtained through a comprehensive search. The outcome measures included response rate, progression-free survival, overall survival, and adverse events (AEs. The hazard ratio (HR, Cochran-Mantel-Haenszel odds ratio (OR, and 95% confidence interval (95% CI were applied to evaluate the effect of bortezomib in relation to the end points such as progression-free survival, overall survival, response rate, and AEs.Results: Three randomized controlled trials comprising 1,518 participants were included in this study. Pooled ORs for the rates of overall response, and complete response and near complete response, were 1.85 and 1.75, respectively. Pooled HR for progression-free survival favored bortezomib-based therapy over non-bortezomib-based therapy (0.73, 95% CI: 0.67–0.81, while no statistically significant difference could be found between the two groups regarding the pooled HR for 3-year overall survival. Moreover, incidence rates of overall adverse events and grade 3 and 4 peripheral neuropathy were similar in the bortezomib-based groups and the non-bortezomib-based groups (P=0.12 and P=0.41, respectively. The corresponding cumulative meta-analyses of the rates of overall response rate, complete response and near complete response, and grades 3 and 4 peripheral neuropathy supported the superiority of bortezomib-based maintenance therapy over consolidation therapy.Conclusion: Bortezomib-based therapy after

  11. Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.

    Science.gov (United States)

    Xie, Jing-Dun; Chen, Shao-Rui; Chen, Hong; Pan, Hui-Lin

    2017-09-01

    Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yanhong; Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2015-02-15

    Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib.

  13. EPR trademark project delivery. The value of experience

    International Nuclear Information System (INIS)

    Leverenz, Ruediger

    2013-01-01

    We are building the EPR trademark reactor fleet. Together. With four EPR trademark projects under construction in the world, AREVA has unrivalled experience in the delivery of large-scale nuclear projects, including more than a thousand lessons learned captured from Olkiluoto 3 and Flamanville 3 projects. This book of knowledge as well as the return of experience of AREVA's and EDF's teams are now being fully leveraged on ongoing projects, especially on Flamanville 3 and Taishan, and will be incorporated in all future EPR TM projects.

  14. Data for a proteomic analysis of p53-independent induction of apoptosis by bortezomib

    Directory of Open Access Journals (Sweden)

    Azmi Yerlikaya

    2014-12-01

    Full Text Available This data article contains data related to the research article entitled, “A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line” by Yerlikaya et al. [1]. The research article presented 2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib-induced changes in the expression of cellular proteins. The report showed that GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for 24 h. In addition, the report demonstrated that Hsp70, the 26S proteasome non-ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in p53-deficient 4T1 cells. The data here show for the first time the increased expressions of Card10, Dffb, Traf3 and Trp53bp2 in response to inhibition of the 26S proteasome. The information presented here also shows that both Traf1 and Xiap (a member of IAPs are also downregulated simultaneously upon proteasomal inhibition. The increases in the level of Card10 and Trp53bp2 proteins were verified by Western blot analysis in response to varying concentrations of bortezomib for 24 h.

  15. Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice.

    Science.gov (United States)

    Bruna, Jordi; Udina, Esther; Alé, Albert; Vilches, Jorge J; Vynckier, Ann; Monbaliu, Johan; Silverman, Lee; Navarro, Xavier

    2010-06-01

    Bortezomib, a proteasome inhibitor, is an antineoplastic drug to treat multiple myeloma and mantle cell lymphoma. Its most clinically significant adverse event is peripheral sensory neuropathy. Our objective was to characterize the neuropathy induced by bortezomib in a mouse model. Two groups were used; one group received vehicle solution and another bortezomib (1mg/kg/twice/week) for 6weeks (total dose as human schedule). Tests were performed during treatment and for 4weeks post dosing to evaluate electrophysiological, autonomic, pain sensibility and sensory-motor function changes. At the end of treatment and after washout, sciatic and tibial nerves, dorsal ganglia and intraepidermal innervation were analyzed. Bortezomib induced progressive significant decrease of sensory action potential amplitude, mild reduction of sensory velocities without effect in motor conductions. Moreover, it significantly increased pain threshold and sensory-motor impairment at 6weeks. According to these data, histopathological findings shown a mild reduction of myelinated (-10%; p=0.001) and unmyelinated fibers (-27%; p=0.04), mostly involving large and C fibers, with abnormal vesicular inclusion body in unmyelinated axons. Neurons were also involved as shown by immunohistochemical phenotypic switch. After washout, partial recovery was observed in functional, electrophysiological and histological analyses. These results suggest that axon and myelin changes might be secondary to an initial dysfunctional neuronopathy. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  16. Bortezomib resistance in multiple myeloma is associated with increased serine synthesis

    NARCIS (Netherlands)

    Zaal, Esther A; Wu, Wei; Jansen, Gerrit; Zweegman, Sonja; Cloos, Jacqueline; Berkers, Celia R

    2017-01-01

    BACKGROUND: The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an important role in cancer development and aid in the cellular adaptation to

  17. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty...

  18. A practical update on the use of bortezomib in the management of multiple myeloma

    NARCIS (Netherlands)

    J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); A. Glasmacher; S. Jagannath (Sundar); S. Lonial (Sagar); R.Z. Orlowski (Robert); P. Sonneveld (Pieter); H. Ludwig (Heinz)

    2006-01-01

    textabstractDespite intensive therapy, multiple myeloma (MM) remains an incurable disease, and novel treatment approaches are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the U.S. Food and Drug Administration (FDA) and the European Agency for

  19. Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

    Directory of Open Access Journals (Sweden)

    Salzer Shanta

    2007-12-01

    Full Text Available Abstract Background COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors. Methods Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days, in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily. Results No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease. Conclusion The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated. Trial registration number NCT00290680.

  20. Thrombotic microangiopathy associated with bortezomib treatment in a patient with relapsed multiple myeloma

    Directory of Open Access Journals (Sweden)

    Urpu Salmenniemi

    2012-06-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP and hemolytic-uremic syndrome (HUS describe microvascular occlusive disorders characterized by thrombocytopenia due to increased platelet aggregation and fragmentation hemolysis. We report here what to our knowledge is the second case of TTP/HUS associated with bortezomib treatment.

  1. From the Stadium Parking Lot to the Information Superhighway: How To Protect Your Trademarks from Infringement.

    Science.gov (United States)

    Bearby, Scott; Siegal, Bruce

    2002-01-01

    Provides an overview of collegiate trademark cases; discusses several forms of infringement, including traditional infringement on commercial products, ambush marketing, and Internet infringement; addresses available remedies; and offers practical tips for dealing effectively with trademark protection. (EV)

  2. Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Myelodysplastic syndromes (MDS are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML. Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells.SKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI values. Western blot was used to analysis phosphorylation of Akt and nuclear NF-κB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151.Simultaneous exposure to HHT and Bortezomib (10.4:1 resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05. Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05. HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01. The mechanisms of the synergy involved Akt and NF-κB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01.HHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-κB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR-3151 abundance is implicated in SKM-1 cell viability, cell

  3. A phase II trial of tamoxifen and bortezomib in patients with recurrent malignant gliomas.

    Science.gov (United States)

    Odia, Yazmín; Kreisl, Teri N; Aregawi, Dawit; Innis, Ellen K; Fine, Howard A

    2015-10-01

    NF-kB inhibition by bortezomib enhances tamoxifen-induced apoptosis in preclinical glioma models. We conducted a single institution, phase II trial to evaluate efficacy and safety of high dose tamoxifen with bortezomib in adults with recurrent malignant gliomas. The primary endpoint was radiographic response. Concurrent enzyme inducing anticonvulsants and grade ≥2 peripheral neuropathy were exclusion criteria. Patients received tamoxifen (120 mg PO twice daily) and bortezomib (1.3 mg/m2 IV on days 3, 6, 10, 13, 24, 27, 31, and 34) per 6-week cycles. We enrolled 42 patients with anaplastic gliomas (AGs, n = 12) and glioblastomas (GBMs, n = 30), 32 males and 10 females. Median age was 38 years (range 22-65) and 48 years (range 19-68) for AGs and GBMs, respectively. median karnofsky performance status was 90% (range 70-100) for AGs and 80% (range 60-100) for GBMs. Median prior therapies was 3, ranging 1-7. Grade ≥3 toxicities included lymphopenia (4/42), hypophosphatemia (3/42), thromobocytopenia (2/42), and 1/42 with hyponatremia, headache, dyspnea, or DVT. One patient withdrew consent, two were removed for toxicity, and all others discontinued for progression. Among 40 patients evaluable for response, only one achieved stable disease for 3 months; all others progressed rapidly. For AGs and GBMs respectively, median progression-free survival was 5.9 and 5.7 weeks and median overall survival was 25.6 and 14.7 weeks. The study was closed due to poor accrual and therapeutic futility. Combination tamoxifen and bortezomib has no activity in recurrent malignant gliomas. Poor penetration across blood brain barrier of bortezomib likely limited efficacy.

  4. 31 CFR 586.512 - Certain transactions related to patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ..., Authorizations, and Statements of Licensing Policy § 586.512 Certain transactions related to patents, trademarks and copyrights authorized. (a) All of the following transactions in connection with patent, trademark... patents, trademarks and copyrights authorized. 586.512 Section 586.512 Money and Finance: Treasury...

  5. 31 CFR 585.515 - Certain transactions related to patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... Licensing Policy § 585.515 Certain transactions related to patents, trademarks and copyrights authorized. (a) All of the following transactions in connection with patent, trademark, copyright, or other... patents, trademarks and copyrights authorized. 585.515 Section 585.515 Money and Finance: Treasury...

  6. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80 + trademark Standard Design. This volume 10 discusses the Steam and Power Conversion System and Radioactive Waste Management

  7. 75 FR 69921 - Trademark Manual of Examining Procedure, Seventh Edition

    Science.gov (United States)

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE... States Patent and Trademark Office, Commerce. ACTION: Notice. SUMMARY: The United States Patent and... be submitted via electronic mail message to [email protected] . Written comments may also be submitted...

  8. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80 + trademark Standard Design. This volume 9 discusses Electric Power and Auxiliary Systems

  9. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80 + trademark Standard Design. This volume 8 provides a description of instrumentation and controls

  10. System 80+trademark Standard Design: CESSAR design certification. Volume 25

    International Nuclear Information System (INIS)

    1997-01-01

    This report has been prepared in support of the industry effort to standardize nuclear plant designs. This document describes the Combustion Engineering, Inc. System 80+trademark Standard Design. This volume contains sections 12 thru 16 of Chapter 19 -- Probabilistic Risk Assessment. Topics covered are: containment response analysis; consequence analysis; containment response and consequence analysis sensitivity analysis; summary and conclusions; and references

  11. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80+trademark Standard Design. This Volume 18 provides Appendix B, Probabilistic Risk Assessment

  12. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describes the Combustion Engineering, Inc. System 80+trademark Standard Design. This Volume 17 provides Appendix A of this report, closure of unresolved and Genetic Safety Issues

  13. Convergence of Trademark Law and E-Commerce

    African Journals Online (AJOL)

    Naumovski & Chapkanov

    also highlights the importance of intellectual property rights for economic ... One of the most cited definition of trademarks is the one given in article 15 of TRIPS1 ..... Romer, P. (1990), Endogenous Technological Change, The Journal of Political. Economy, Vol. 98, No. 5, Part 2: The Problem of Development: A Conference of.

  14. System 80+trademark standard design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report--Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These documents describe the Combustion Engineering, Inc. System 80+trademark Standard Design. This report, Volume 13, documents increase and decrease of reactor cooling system inventory and radioactive material release from a subsystem or component

  15. 75 FR 38543 - Patent, Trademark and Copyright Acts

    Science.gov (United States)

    2010-07-02

    ... DEPARTMENT OF THE INTERIOR Geological Survey Patent, Trademark and Copyright Acts AGENCY: Geological Survey, Interior. ACTION: Notice of prospective intent to award exclusive license. SUMMARY: The... Technologies Group, Inc., 253 Portman Lane, Suite 107, Bridgeville, PA 15017 on U.S. Patent No. 6,485,696 B1...

  16. System 80+trademark Standard Design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report, entitled Combustion Engineering Standard Safety Analysis Report - Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80+trademark Standard Design. This Volume 16 details the application of Human Factors Engineering in the design process

  17. The European Legislation and Protection of Trademarks in Romania

    Directory of Open Access Journals (Sweden)

    Codruta Stefania Jucan

    2011-05-01

    Full Text Available Objective: The present paper aims at producing a brief account and analysis of the changes thathave been made to the Romanian Trademark Law during the last few years in order to achieve harmonizationwith the European Trademark Law. Prior Work: The subject is being researched especially by the authorsfrom abroad and only the last years brought new investigations from the Romanians. Approach: The presentpaper was put together using a synthesis and analytical approach, taking in account different sources fromlegislation, court cases to papers that have been written about the subject. Results: The result of this studyindicates a way of harmonizing the internal legislation of Romania with that of the E.U on the subject andfuture directions of Trademark Law. Implications: The present study does its part in the intellectual propertystudies research area, offering a better view on the problems regarding the trademark law and itsnaturalization in the legal systems of the member states. Value: The study at hand is of great value inunderstanding the problems and challenges in the harmonization of legal concepts using the example ofIntellectual Property Rights in the U.E.

  18. Future{at}Labs.Prosperity Game{trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Beck, D.F.; Boyack, K.W.; Berman, M. [Sandia National Labs., Albuquerque, NM (United States). Innovative Alliances Dept.

    1996-10-01

    Prosperity Games{trademark} are an outgrowth and adaptation of move/countermove and seminar War Games, Prosperity Games{trademark} are simulations that explore complex issues in a variety of areas including economics, politics, sociology, environment, education, and research. These issues can be examined from a variety of perspectives ranging from global, macroeconomic and geopolitical viewpoint down to the details of customer/supplier/market interactions specific industries. All Prosperity Games{trademark} are unique in that both the game format and the player contributions vary from game to game. This report documents the Future{at}Labs.Prosperity Game{trademark} conducted under the sponsorship of the Industry Advisory Boards of the national labs, the national labs, Lockheed Martin Corporation, and the University of California. Players were drawn from all stakeholders involved including government, industry, labs, and academia. The primary objectives of this game were to: (1) explore ways to optimize the role of the multidisciplinary labs in serving national missions and needs; (2) explore ways to increase collaboration and partnerships among government, laboratories, universities, and industry; and (3) create a network of partnership champions to promote findings and policy options. The deliberations and recommendations of these players provided valuable insights as to the views of this diverse group of decision makers concerning the future of the labs.

  19. System 80+{trademark} standard design incorporates radiation protection lessons learned

    Energy Technology Data Exchange (ETDEWEB)

    Crom, T.D.; Naugle, C.L. [Duke Engineering & Services, Inc., Charlotte, NC (United States); Turk, R.S. [ABB Combustion Engineering Nuclear Power, Windsor, CT (United States)

    1995-03-01

    Many lessons have been learned from the current generation of nuclear plants in the area of radiation protection. The following paper will outline how the lessons learned have been incorporated into the design and operational philosophy of the System 80+{trademark} Standard Design currently under development by ABB Combustion Engineering (ABB-CE) with support from Duke Engineering and Services, Inc. and Stone and Webster Engineering Corporation in the Balance-of-Plant design. The System 80+{trademark} Standard Design is a complete nuclear power plant for national and international markets, designed in direct response to utility needs for the 1990`s, and scheduled for Nuclear Regulatory Commission (NRC) Design Certification under the new standardization rule (10 CFR Part 52). System 80+{trademark} is a natural extension of System 80{sup R} technology, an evolutionary change based on proven Nuclear Steam Supply System (NSSS) in operation at Palo Verde in Arizona and under construction at Yonggwang in the Republic of Korea. The System 80+{trademark} Containment and much of the Balance of Plant design is based upon Duke Power Company`s Cherokee Plant, which was partially constructed in the late 1970`s, but, was later canceled (due to rapid declined in electrical load growth). The System 80+{trademark} Standard Design meets the requirements given in the Electric Power Research Institute (EPRI) Advanced Light Water Reactor (ALWR) Requirements Document. One of these requirements is to limit the occupational exposure to 100 person-rem/yr. This paper illustrates how this goal can be achieved through the incorporation of lessons learned, innovative design, and the implementation of a common sense approach to operation and maintenances practices.

  20. Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib

    DEFF Research Database (Denmark)

    Nijhof, I. S.; Groen, R. W. J.; Noort, W. A.

    2015-01-01

    Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new...... with lenalidomide or bortezomib for the treatment of lenalidomide- and bortezomib-refractory patients. Experimental Design: In ex vivo assays, mainly evaluating antibody-dependent cell-mediated cytotoxicity, and in an in vivo xenograft mouse model, we evaluated daratumumab alone or in combination with lenalidomide...... or bortezomib as a potential therapy for lenalidomide- and bortezomib-refractory multiple myeloma patients. Results: Daratumumab induced significant lysis of lenalidomide/bortezomib-resistant multiple myeloma cell lines and of primary multiple myeloma cells in the bone marrow mononuclear cells derived from...

  1. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    Science.gov (United States)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels; Garnero, Patrick; Pedersen, Per T; Ormstrup, Tina; Delaissé, Jean-Marie; Plesner, Torben

    2010-01-01

    Objectives: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions: Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. PMID:20528908

  2. Establishing a Collegiate Trademark Licensing Program: To What Extent Does an Institution Have an Exclusive Right to Its Name?

    Science.gov (United States)

    Schinner, Michael G.

    1989-01-01

    One aspect of universities becoming "big business" is the marketing and protection of trademarks. Universities have resorted to trademark infringement suits or licensing agreements. The historical purposes of trademark registration, the problems with litigating trademark infringement, and the advantages and disadvantages of licensing…

  3. 31 CFR 500.528 - Certain transactions with respect to blocked foreign patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... Licensing Policy § 500.528 Certain transactions with respect to blocked foreign patents, trademarks and... blocked foreign patents, trademarks and copyrights authorized. 500.528 Section 500.528 Money and Finance..., trademark or copyright, or for the renewal thereof; (2) The receipt of any blocked foreign patent, trademark...

  4. System 80+trademark Standard Design: CESSAR design certification. Volume 8

    International Nuclear Information System (INIS)

    1997-01-01

    This report has been prepared in support of the industry effort to standardize nuclear plant designs. This document describes the Combustion Engineering, Inc. System 80+trademark Standard Design. This volume contains Chapter 7 -- Instrumentation and Controls. Topics covered are: reactor protection system; engineered safety feature actuation systems; systems required for safe shutdown; safety-related display instrumentation; all other instrumentation for safety; and control systems not required for safety. Appendix 7A is included

  5. Connecting icons, logos and slogans in graphic trademarks

    OpenAIRE

    Ambrožič, Maja

    2016-01-01

    In the public eye the organization is always considered or fully represented by its corporate identity that includes the size of the organization, annual payments, organizational structure, organizational culture, systems owned by the organization, premises, organizational culture, organizational strategy, mission, vision, number of employees etc. Graphic designer when designing graphic trademark by connecting graphic elements (logo, slogan and icon) must take in to consideration all abovemen...

  6. A Multimodal Approach to Meaning-Making in Trademarks

    DEFF Research Database (Denmark)

    Johannessen, Christian Mosbæk

    2008-01-01

    When enterprises go to court to settle disputes over confusable graphic trademarks and intellectual property, they usually present evidence to the nature of the design of the involved marks, which is based on subjective judgment – usually on the part of an appraiser with a professional background...... of the human body, whereas the PR marks is the result of an abstract formalized and stylized use of the same resources known from typography....

  7. Application of MCNP{trademark} to computed tomography in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Brockhoff, R.C. [KSU (United States); Estes, G.P.; Hills, C.R. [Mason and Hanger (United States); Demarco, J.J.; Solberg, T.D. [California Univ., Los Angeles, CA (United States)

    1996-03-01

    The MCNP{trademark} code has been used to simulate CT scans of the MIRD human phantom. In addition. an actual CT scan of a patient was used to create an MCNP geometry, and this geometry was computationally ``CT scanned`` using MCNP to reconstruct CT images. The results show that MCNP can be used to model the human body based on data obtained from CT scans and to simulate CT scans that are based on these or other models.

  8. Radiant{trademark} Liquid Radioisotope Intravascular Radiation Therapy System

    Energy Technology Data Exchange (ETDEWEB)

    Eigler, N.; Whiting, J.; Chernomorsky, A.; Jackson, J.; Knapp, F.F., Jr.; Litvack, F.

    1998-01-16

    RADIANT{trademark} is manufactured by United States Surgical Corporation, Vascular Therapies Division, (formerly Progressive Angioplasty Systems). The system comprises a liquid {beta}-radiation source, a shielded isolation/transfer device (ISAT), modified over-the-wire or rapid exchange delivery balloons, and accessory kits. The liquid {beta}-source is Rhenium-188 in the form of sodium perrhenate (NaReO{sub 4}), Rhenium-188 is primarily a {beta}-emitter with a physical half-life of 17.0 hours. The maximum energy of the {beta}-particles is 2.1 MeV. The source is produced daily in the nuclear pharmacy hot lab by eluting a Tungsten-188/Rhenium-188 generator manufactured by Oak Ridge National Laboratory (ORNL). Using anion exchange columns and Millipore filters the effluent is concentrated to approximately 100 mCi/ml, calibrated, and loaded into the (ISAT) which is subsequently transported to the cardiac catheterization laboratory. The delivery catheters are modified Champion{trademark} over-the-wire, and TNT{trademark} rapid exchange stent delivery balloons. These balloons have thickened polyethylene walls to augment puncture resistance; dual radio-opaque markers and specially configured connectors.

  9. Implementation of a funnel-and-gate trademark remediation system

    International Nuclear Information System (INIS)

    O'Brien, K.; Keyes, G.; Sherman, N.

    1997-01-01

    Funnel-and-gate trademark systems are gaining attention, not necessarily because they speed up the remediation process, but because their use recognizes the limitations of groundwater cleanup programs and factors these limitations into minimizing the lifetime costs of implementing remedial actions. The term funnel-and-gate refers to the installation of low-permeability barriers downgradient of impacted groundwater which are arranged so as to direct the flow of the groundwater through treatment gates. The flow through the treatment gates is driven by natural groundwater gradients, eliminating extraction pumps and above-ground treatment systems. The treatment gates are designed specifically to treat the contamination in the groundwater that will flow through the gates. Funnel-and-gate trademark systems attempt to eliminate or at least minimize mechanical systems, thereby reducing the long-term operation and maintenance costs that so often drive up the lifetime costs of remedial projects. Long-term operation and maintenance costs are reduced because the site does not need a continuous input of energy or manpower. In addition, groundwater monitoring and system compliance issues can be streamlined for even greater cost savings. Since it is a developing technology, there are few commercial applications where funnel-and-gate trademark systems have been proven. Concurrent with groundwater investigations, a number of remedial actions had been undertaken at a property in California. Underground storage tanks which contain diesel fuels were excavated and removed. A former dry well suspected of being the source of chlorinated-solvent impacts was also excavated

  10. SHORT CONSIDERATIONS ON THE USE OF TRADE INDICATORS AS TRADEMARKS

    Directory of Open Access Journals (Sweden)

    PAUL-GEORGE BUTA

    2012-05-01

    Full Text Available In today's global marketplace products and services are exchanged internationally not only by large companies wielding a large portfolio of internationally protected trademarks but also by small enterprises and even individuals who have neither the resources nor an interest in the building of such a portfolio. Since they are nonetheless economic agents using either their own or others' trade indicators to indicate the origin and quality of the products and services they provide or simply to advertise them, the present paper addresses some of the issues arising out of that use which is akin to trademark use in what regards said products and services. Special attention is paid to the change in purpose of the trade indicators when used as trademarks and the effects said change causes in the legal protection conferred to those trade indicators. Moreover the possible conflicts between such rights are shortly analyzed and the means for resolution of such conflicts briefly reviewed. Far from being an exhaustive study of the issues raised the present paper aims at identifying these issues and pointing to contentious points to be addressed by future research.

  11. Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Tatsuro Joh

    2009-10-01

    Full Text Available We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6. Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies.

  12. Management of Multiple Myeloma and Usage of Bortezomib: Perspective from India and Ukraine

    Directory of Open Access Journals (Sweden)

    India and Ukraine Haemato-oncology Group

    2016-11-01

    Full Text Available Novel treatment strategies have remarkably improved the multiple myeloma (MM patients’ survival, with associated increased costs.A joint panel meet of international experts from India and Ukraine was held in New Delhi on 19th May 2016 focusing on: MM management, bortezomib role, unmet medical needs, and current challenges.The healthcare system for oncology in India is majorly private versus government-based in Ukraine. In India, electrophoresis, serum-free light chain assays, bone marrow tests, and X-rays are available modes of diagnosis. Despite of the numerous cancer centers and stem cell transplant centers, most patients do not prefer transplant owing to its high-cost and social stigma. Majority of the patients are treated with bortezomib or lenalidomide-based regimens. Most patients buy drug themselves. The expanding generic drugs market is a ray of hope for the affordable drugs.In Ukraine, immuno-fixation, bone-marrow analysis, and magnetic-resonance-imaging are common diagnostic modalities. Due to high-cost, only few patients undergo transplant. Bortezomib-based regimens are preferred in most of the patients, however usage is limited due to high costs and lack of funds. Thalidomide-based regimens are used for maintenance therapy due to affordability. In case of relapsed MM, bortezomib is preferred in triple therapy, however more affordable option is cyclophosphamide, thalidomide, and dexamethasone (CTD. Issues such as cost containment, common treatment strategies, enhanced collaboration, and improved healthcare access need immediate attention. High-quality generics access will improve outcomes and support healthcare cost containment. Pharmacoeconomic studies and head-to-head trials are warranted to determine the cost-effectiveness and benefit of novel therapies in MM.

  13. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis.

    Science.gov (United States)

    Kastritis, Efstathios; Wechalekar, Ashutosh D; Dimopoulos, Meletios A; Merlini, Giampaolo; Hawkins, Philip N; Perfetti, Vittorio; Gillmore, Julian D; Palladini, Giovanni

    2010-02-20

    PURPOSE To assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both. PATIENTS AND METHODS Ninety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Results A hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of > or = 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea. CONCLUSION Bortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.

  14. A Novel Gallium Compound Synergistically Enhances Bortezomib-induced Apoptosis in Mantle Cell Lymphoma Cells

    OpenAIRE

    Chitambar, Christopher R.; Purpi, David P.

    2010-01-01

    Combination chemotherapy forms the backbone of cancer treatment. There is a need for new drug combinations for the treatment of mantle cell lymphoma (MCL). Herein, we show that gallium maltolate, a novel gallium compound, synergizes with bortezomib, a proteasome inhibitor, to induce cell death in MCL Granta cells. Cells exposed to either agent displayed caspase-3 activation, a loss of mitochondrial membrane potential, and a decrease in chymotrypsin-like activity. These effects were increased ...

  15. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

    Directory of Open Access Journals (Sweden)

    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  16. Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39: A Gene Expression Study

    Directory of Open Access Journals (Sweden)

    Hakan Savlı

    2015-09-01

    Full Text Available Objective: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39. Materials and Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR. Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings. Conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS. NF-κB was observed as an important modulator in leukemic transformation of MDS.

  17. Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis.

    Science.gov (United States)

    Sun, Chun-Yan; Li, Jun-Ying; Chu, Zhang-Bo; Zhang, Lu; Chen, Lei; Hu, Yu

    2017-08-31

    Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P =0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P =0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P =0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P =0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM. © 2017 The Author(s).

  18. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

    International Nuclear Information System (INIS)

    Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m 2 per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m 2 and escalation levels of 1.0 and 1.3 mg/m 2 . Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m 2 (7 patients), 1.0 mg/m 2 (10 patients), and 1.3 mg/m 2 (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m 2 in patients previously treated for HNC and 1.3 mg/m 2 in radiation-naive patients.

  19. Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.

    Science.gov (United States)

    Dasmahapatra, Girija; Lembersky, Dmitry; Rahmani, Mohamed; Kramer, Lora; Friedberg, Jonathan; Fisher, Richard I; Dent, Paul; Grant, Steven

    2009-05-01

    Mechanisms underlying interactions between the proteasome inhibitor bortezomib and small molecule Bcl-2 antagonists were examined in GC- and ABC-type human DLBCL (diffuse lymphocytic B-cell lymphoma) cells. Concomitant or sequential exposure to non- or minimally toxic concentrations of bortezomib or other proteasome inhibitors and either HA14-1 or gossypol resulted in a striking increase in Bax/Bak conformational change/translocation, cytochrome c release, caspase activation and synergistic induction of apoptosis in both GC- and ABC-type cells. These events were associated with a sharp increase in activation of the stress kinase JNK and evidence of ER stress induction (e.g., eIF2alpha phosphorylation, activation of caspases-2 and -4, and Grp78 upregulation). Pharmacologic or genetic (e.g., shRNA knockdown) interruption of JNK signaling attenuated HA14-1/bortezomib lethality and ER stress induction. Genetic disruption of the ER stress pathway (e.g., in cells expressing caspase-4 shRNA or DN-eIF2alpha) significantly attenuated lethality. The toxicity of this regimen was independent of ROS generation. Finally, HA14-1 significantly increased bortezomib-mediated JNK activation, ER stress induction, and lethality in bortezomib-resistant cells. Collectively these findings indicate that small molecule Bcl-2 antagonists promote bortezomib-mediated mitochondrial injury and lethality in DLBCL cells in association with enhanced JNK activation and ER stress induction. They also raise the possibility that such a strategy may be effective in different DLBCL sub-types (e.g., GC- or ABC), and in bortezomib-resistant disease.

  20. Phase I Trial Using the Proteasome Inhibitor Bortezomib and Concurrent Chemoradiotherapy for Head-and-Neck Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kubicek, Gregory J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Axelrod, Rita S. [Department of Medical Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Machtay, Mitchell [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States); Ahn, Peter H.; Anne, Pramila R. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Fogh, Shannon [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Cognetti, David [Department of Otolaryngology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Myers, Thomas J. [EMD Serono, Rockland, MA (United States); Curran, Walter J. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P., E-mail: Adam.dicker@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-07-15

    Purpose: Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials: Eligible patients received cisplatin once weekly at 30 mg/m{sup 2} per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m{sup 2} and escalation levels of 1.0 and 1.3 mg/m{sup 2}. Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results: We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m{sup 2} (7 patients), 1.0 mg/m{sup 2} (10 patients), and 1.3 mg/m{sup 2} (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion: Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m{sup 2} in patients previously treated for HNC and 1.3 mg/m{sup 2} in radiation-naive patients.

  1. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy.

    NARCIS (Netherlands)

    Sonneveld, P.; Hajek, R.; Nagler, A.; Spencer, A.; Blade, J.; Robak, T.; Zhuang, S.H.; Harousseau, J.L.; Orlowski, R.Z.

    2008-01-01

    BACKGROUND: Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current

  2. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy

    NARCIS (Netherlands)

    P. Sonneveld (Pieter); R. Hajek (Roman); A. Nagler (Arnon); A. Spencer (Andrew); J. Bladé (Joan); T. Robak (Tadeusz); S.H. Zhuang (Sen); J-L. Harousseau (Jean-Luc); R.Z. Orlowski (Robert)

    2008-01-01

    textabstractBACKGROUND. Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In

  3. Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

    Directory of Open Access Journals (Sweden)

    L. I. Nagy

    2015-01-01

    Full Text Available Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

  4. Schwann cell autophagy induced by SAHA, 17-AAG, or clonazepam can reduce bortezomib-induced peripheral neuropathy

    Science.gov (United States)

    Watanabe, T; Nagase, K; Chosa, M; Tobinai, K

    2010-01-01

    Background: The proteasome inhibitor bortezomib has improved the survival of patients with multiple myeloma but bortezomib-induced peripheral neuropathy (BiPN) has emerged as a serious potential complication of this therapy. Animal studies suggest that bortezomib predominantly causes pathological changes in Schwann cells. A tractable system to evaluate combination drugs for use with bortezomib is essential to enable continuing clinical benefit from this drug. Methods: Rat schwannoma cells were pretreated with vincristine (VCR), histone deacetylase inhibitors, anticonvulsants, or a heat-shock protein 90 (HSP90) inhibitor. To then monitor aggresome formation as a result of proteasome inhibition and the activation of chaperone-mediated autophagy (CMA), we performed double-labelling immunofluorescent analyses of a cellular aggregation-prone protein marker. Results: Aggresome formation was interrupted by VCR, whereas combination treatments with bortezomib involving suberoylanilide hydroxamic acid, 17-allylamino-17-demethoxy-geldanamycin, or clonazepam appear to facilitate the disposal of unfolded proteins via CMA, inducing HSP70 and lysosome-associated membrane protein type 2A (LAMP-2A). Conclusions: This schwannoma model can be used to test BiPN-reducing drugs. The present data suggest that aggresome formation in Schwann cells is a possible mechanism of BiPN, and drugs that induce HSP70 or LAMP-2A have the potential to alleviate this complication. Combination clinical trials are warranted to confirm the relevance of these observations. PMID:20959823

  5. Weekly versus biweekly bortezomib given in patients with indolent non-Hodgkin lymphoma: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ting Yuan

    Full Text Available Bortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain.We did a systematic review and meta-analysis of the clinical trials comparing the efficacy and toxicity of the weekly and biweekly schedules of bortezomib in patients with indolent lymphoma. We searched Pubmed, Cochrane Library and Emabase from inception to July 29, 2016. The primary outcome was the overall response rate including the complete response rate and the partial response rate. The secondary outcomes were the proportions of patients in each group experiencing the adverse events including the neutropathy, fatigue, diarrhea, nausea and neutropenia.After final screening, six trials were considered eligible for analysis. The results showed that the overall response rate of biweekly schedule was higher than that of weekly schedule in indolent lymphoma (OR 1.691;95%CI 1.02-2.80. Furthermore, there were no significant differences between the two schedules of bortezomib for the main adverse events.The biweekly schedule of bortezomib was more effective than the weekly schedule in indolent lymphoma, with similar proportion of toxicities.

  6. Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

    Science.gov (United States)

    San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

    2017-10-01

    Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

  7. Hot cell decontamination at the DOE Hanford site using the KSI Tentacle{trademark} manipulator

    Energy Technology Data Exchange (ETDEWEB)

    Immega, G.; Antonelli, K.; Ko, J. [Kinetic Sciences Inc., Vancouver (Canada)] [and others

    1996-12-31

    The KSI Tentacle{trademark} is a low-cost robotic manipulator functionally and economically ideal for decontaminating and decommissioning operations. This paper reports how Battelle Pacific Northwest Laboratories (PNL) successfully employed a Tentacle{trademark} manipulator to spray-wash the radioactive airlock to the B-Cell hot cell facility at the DOE Hanford site, and considers how else the Tentacle{trademark} might be used at Hanford for decontamination work in the future.

  8. 7 CFR 1216.88 - Patents, copyrights, trademarks, information, publications, and product formulations.

    Science.gov (United States)

    2010-01-01

    ..., residual payments, or other income from the rental, sales, leasing, franchising, or other uses of such patents, copyrights, trademarks, information, publications, or product formulations, inure to the benefit...

  9. The Creation and Use of an Analysis Capability Maturity Model (trademark) (ACMM)

    National Research Council Canada - National Science Library

    Covey, R. W; Hixon, D. J

    2005-01-01

    .... Capability Maturity Models (trademark) (CMMs) are being used in several intellectual endeavors, such as software engineering, software acquisition, and systems engineering. This Analysis CMM (ACMM...

  10. Unsupervised symmetrical trademark image retrieval in soccer telecast using wavelet energy and quadtree decomposition

    Science.gov (United States)

    Ong, Swee Khai; Lim, Wee Keong; Soo, Wooi King

    2013-04-01

    Trademark, a distinctive symbol, is used to distinguish products or services provided by a particular person, group or organization from other similar entries. As trademark represents the reputation and credit standing of the owner, it is important to differentiate one trademark from another. Many methods have been proposed to identify, classify and retrieve trademarks. However, most methods required features database and sample sets for training prior to recognition and retrieval process. In this paper, a new feature on wavelet coefficients, the localized wavelet energy, is introduced to extract features of trademarks. With this, unsupervised content-based symmetrical trademark image retrieval is proposed without the database and prior training set. The feature analysis is done by an integration of the proposed localized wavelet energy and quadtree decomposed regional symmetrical vector. The proposed framework eradicates the dependence on query database and human participation during the retrieval process. In this paper, trademarks for soccer games sponsors are the intended trademark category. Video frames from soccer telecast are extracted and processed for this study. Reasonably good localization and retrieval results on certain categories of trademarks are achieved. A distinctive symbol is used to distinguish products or services provided by a particular person, group or organization from other similar entries.

  11. Theta-Cream trademark versus Bepanthol trademark lotion in breast cancer patients under radiotherapy. A new prophylactic agent in skin care?

    International Nuclear Information System (INIS)

    Roeper, B.; Kaisig, D.; Auer, F.; Mergen, E.; Molls, M.

    2004-01-01

    Background and purpose: in radiotherapy of the breast following breast-conserving surgery, the adverse reaction predominatly found is confined to the skin. After phase II studies, Theta-Cream trademark , containing CM glucan, hydroxyprolisilan C und matrixyl as active substances, was said to have prophylactic properties of preventing acute radiation side effects in skin tissue. In a prospective randomized study, Theta-Cream trademark was compared with standard skin care using Bepanthol trademark lotion. Patients and methods: 20 breast cancer patients were randomly assigned to use Theta-Cream trademark or Bepanthol trademark lotion during radiotherapy. At 0, 30, and 50 Gy, acute skin toxicity was scored with a modified RTOG scoring system. The patients' content with the skin care and the technical assistants' content with the skin marks were recorded. Results: for single aspects of toxicity and their sums in defined skin areas, no differences in median and range between study groups were found. The maximal toxicity anywhere in the breast averaged in a moderate erythema, mild elevation of skin temperature, no desquamation in both groups. Mild itchiness and sporadic efflorescences more frequently seen with Theta-Cream trademark . According to a ranking of anonymized breast photos at 50 Gy by independent investigators, side effects were equal. Patients' content was high with both skin care regimens (1.25 on a scale from 0 to 10). With Theta-Cream trademark a trend toward worse skin marks was noted. Adverse events exclusively occurred in Theta-Cream trademark users: suspected allergic reaction once, and the necessity for resimulation twice. Conclusion: in direct comparison with dexpanthenol-containing lotion, no advantage for Theta-Cream trademark was found. Higher costs and problems with skin marks prevent a general recommendation. (orig.)

  12. MCNP trademark Monte Carlo: A precis of MCNP

    International Nuclear Information System (INIS)

    Adams, K.J.

    1996-01-01

    MCNP trademark is a general purpose three-dimensional time-dependent neutron, photon, and electron transport code. It is highly portable and user-oriented, and backed by stringent software quality assurance practices and extensive experimental benchmarks. The cross section database is based upon the best evaluations available. MCNP incorporates state-of-the-art analog and adaptive Monte Carlo techniques. The code is documented in a 600 page manual which is augmented by numerous Los Alamos technical reports which detail various aspects of the code. MCNP represents over a megahour of development and refinement over the past 50 years and an ongoing commitment to excellence

  13. Cost effectiveness analysis of the SEAMIST trademark membrane system technology

    International Nuclear Information System (INIS)

    Henriksen, A.D.; Booth, S.R.

    1993-01-01

    This report describes the cost and performance characteristics of SEAMIST trademark, an innovative technology that facilitates measurements of contaminants in both vertical and horizontal vadose zone boreholes. This new technology consists of an airtight membrane linear that is pneumatically emplaced inside the borehole structure. Sampling ports with attached tubing, absorbent collectors, or various in situ measuring devices can be fabricated into the linear and used for monitoring volatile organic compounds (VOCs), semivolatile organic compounds (SVOCs), pesticides, herbicides, polynuclear aromatic hydrocarbons, polychlorinated biphenyls, or radioactive substances. In addition, small instruments can be guided through the lined borehole and measurements taken inside at specified intervals

  14. The AMTEX Partnership{trademark}. Fourth quarter report, September 1994

    Energy Technology Data Exchange (ETDEWEB)

    Lemon, D.K.; Quisenberry, R.K.

    1994-06-01

    The AMTEX Partnership{trademark} is a collaborative research and development program among the US Integrated Textile Industry, the Department of Energy (DOE), the DOE laboratories, other federal agencies and laboratories, and universities. The goal of AMTEX is to strengthen the competitiveness of this vital industry, thereby preserving and creating US jobs. The operational and program management of the AMTEX Partnership is provided by the Program Office. This report is produced by the Program Office on a quarterly basis and provides information on the progress, operations, and project management of the partnership.

  15. Development and Positioning of the Collective Product of Slovenian Craft Trademark

    Directory of Open Access Journals (Sweden)

    Adrijana Poljanšek

    2017-09-01

    Full Text Available The new collective trademark Izdelek slovenske obrti (hereinafter: PSC; English: Product of Slovenian Craft was launched on the market in 2014. The initiative for the trademark was provided by the Textile Section at the Chamber of Craft and Small Business of Slovenia (hereinafter: the OZS, which also registered the trademark. Members of the OZS have the right to obtain and use the trademark, and to use it to promote their products or services. After two years, only a small number of section members use the trademark. Because the section would like to see an increased number of members use the trademark, research regarding the latter was carried out. The results are presented in this article. The descriptive course of development and registration of the collective trademark PSC is presented in the first part of our research. In the second part, questionnaires were drafted for collective trademark PSC users, potential users and consumers. The results obtained using three questionnaires were analysed using a SWOT analysis. Based on the results, it was determined that the trademark has not yet been properly positioned on the Slovenian market. Advantages include the familiarity of Textile Section members with the trademark, and their eagerness to use it. One disadvantage is the trademark’s current lack of recognition among consumers. For this reason, section members who are also potential users of the trademark do not give it priority and therefore do not opt to use it. The following will impact the trademark’s recognition among consumers: innovative marketing campaigns, the inclusion of the media and social networks, the improved recognition and visibility of the logotype, and an effective and pervasive slogan, as was determined in our research.

  16. SEAMIST trademark soil sampling for tritiated water: First year's results

    International Nuclear Information System (INIS)

    Mallon, B.; Martins, S.A.; Houpis, J.L.; Lowry, W.; Cremer, C.D.

    1992-01-01

    SEAMIST trademark is a recently developed sampling system that enables one to measure various soil parameters by means of an inverted, removable, impermeable membrane tube inserted in a borehole. This membrane tube can have various measuring devices installed on it, such as gas ports, adsorbent pads, and electrical sensors. These membrane tubes are made of a laminated polymer. The Lawrence Livermore National Laboratory in Livermore, California, has installed two of these systems to monitor tritium in soil resulting from a leak in an underground storage tank. One tube is equipped with gas ports to sample soil vapor and the other with adsorbent pads to sample soil moisture. Borehole stability was maintained using either sand-filled or air-inflated tubes. Both system implementations yielded concentrations or activities that compared well with the measured concentrations of tritium in the soil taken during borehole construction. In addition, an analysis of the data suggest that both systems prevented the vertical migration of tritium in the boreholes. Also, a neutron probe was successfully used in a blank membrane inserted in one of the boreholes to monitor the moisture in the soil without exposing the probe to the tritium. The neutron log showed excellent agreement with the soil moisture content measured in soil samples taken during borehole construction. This paper describes the two SEAMIST trademark systems used and presents sampling results and comparisons

  17. Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib.

    Science.gov (United States)

    Lecis, D; Drago, C; Manzoni, L; Seneci, P; Scolastico, C; Mastrangelo, E; Bolognesi, M; Anichini, A; Kashkar, H; Walczak, H; Delia, D

    2010-06-08

    XIAP (X-linked inhibitor of apoptosis protein) is an anti-apoptotic protein exerting its activity by binding and suppressing caspases. As XIAP is overexpressed in several tumours, in which it apparently contributes to chemoresistance, and because its activity in vivo is antagonised by second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis-binding protein with low pI, small molecules mimicking SMAC (so called SMAC-mimetics) can potentially overcome tumour resistance by promoting apoptosis. Three homodimeric compounds were synthesised tethering a monomeric SMAC-mimetic with different linkers and their affinity binding for the baculoviral inhibitor repeats domains of XIAP measured by fluorescent polarisation assay. The apoptotic activity of these molecules, alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or Bortezomib, was tested in melanoma cell lines by MTT viability assays and western blot analysis of activated caspases. We show that in melanoma cell lines, which are typically resistant to chemotherapeutic agents, XIAP knock-down sensitises cells to TRAIL treatment in vitro, also favouring the accumulation of cleaved caspase-8. We also describe a new series of 4-substituted azabicyclo[5.3.0]alkane monomeric and dimeric SMAC-mimetics that target various members of the IAP family and powerfully synergise at submicromolar concentrations with TRAIL in inducing cell death. Finally, we show that the simultaneous administration of newly developed SMAC-mimetics with Bortezomib potently triggers apoptosis in a melanoma cell line resistant to the combined effect of SMAC-mimetics and TRAIL. Hence, the newly developed SMAC-mimetics effectively synergise with TRAIL and Bortezomib in inducing cell death. These findings warrant further preclinical studies in vivo to verify the anticancer effectiveness of the combination of these agents.

  18. Bortezomib-induced peripheral neuropathy: A genome-wide association study on multiple myeloma patients.

    Science.gov (United States)

    Campo, Chiara; da Silva Filho, Miguel Inacio; Weinhold, Niels; Mahmoudpour, Seyed Hamidreza; Goldschmidt, Hartmut; Hemminki, Kari; Merz, Maximilian; Försti, Asta

    2018-02-01

    The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment. We identified 4 new promising loci for bortezomib-induced PNP at 4q34.3 (rs6552496), 5q14.1 (rs12521798), 16q23.3 (rs8060632), and 18q21.2 (rs17748074). Even though the results did not reach genome-wide significance level, they support the idea of previous studies, suggesting a genetic basis for neurotoxicity. The identified single nucleotide polymorphisms map to genes or next to genes involved in the development and function of the nervous system (CDH13, DCC, and TENM3). As possible functional clues, 2 of the variants, rs12521798 and rs17748074, affect enhancer histone marks in the brain. The rs12521798 may also impact expression of THBS4, which affects specific signal trasduction pathways in the nervous system. Further research is needed to clarify the mechanism of action of the identified single nucleotide polymorphisms in the development of drug-induced PNP and to functionally validate our in silico predictions. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    T. A. Мitinа

    2015-01-01

    Full Text Available 49 patients aged 28 to 81 years old (median age of 55 years old with relapsed or refractory multiple myeloma (MM were enrolled in the study. The relapse was diagnosed in 25 (51 % patients, the refractory disease was determined in 24 (49 % patients (including primary refractory disease in 14 (28.6 % patients. The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %. Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP. The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR in 1 (2 % patient; very good partial response (VGPR in 4 (8 % patients; partial response (PR in 26 (53 % patients; minimal response (MR in 2 (4 % patients; stable disease (SD in 8 (16.3 % patients, and progressive disease (PD in 8 (16.3 % patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 % patients. The objective response rate, including MR, was seen in 33 (67.1 % patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

  20. Vorinostat in combination with bortezomib in patients with advanced malignancies directly alters transcription of target genes.

    Science.gov (United States)

    Kolesar, Jill M; Traynor, Anne M; Holen, Kyle D; Hoang, Tien; Seo, Songwon; Kim, Kyungmann; Alberti, Dona; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H; Schelman, William R

    2013-09-01

    Vorinostat is a small molecule inhibitor of class I and II histone deacetylase enzymes which alters the expression of target genes including the cell cycle gene p21, leading to cell cycle arrest and apoptosis. Patients enrolled in a phase I trial were treated with vorinostat alone on day 1 and vorinostat and bortezomib in combination on day 9. Paired biopsies were obtained in eleven subjects. Blood samples were obtained on days 1 and 9 of cycle 1 prior to dosing and 2 and 6 h post-dosing in all 60 subjects. Gene expression of p21, HSP70, AKT, Nur77, ERB1, and ERB2 was evaluated in peripheral blood mononuclear cells and tissue samples. Chromatin immunoprecipitation of p21, HSP70, and Nur77 was also performed in biopsy samples. In peripheral blood mononuclear cells, Nur77 was significantly and consistently decreased 2 h after vorinostat administration on both days 1 and 9, median ratio of gene expression relative to baseline of 0.69 with interquartile range 0.49-1.04 (p vorinostat and bortezomib. p21, a downstream target of Nur77, was significantly decreased on day 9, 2 and 6 h after administration of vorinostat and bortezomib, 0.67 (0.41-1.03) (p vorinostat in tissue biopsies in most patients. Vorinostat inhibits Nur77 expression, which in turn may decrease p21 and AKT expression in PBMCs. The influence of vorinostat on target gene expression in tumor tissue was variable; however, most patients demonstrated interaction of acetylated H3 with Nur77, HSP70, and p21 which provides evidence of interaction with the transcriptionally active acetylated H3.

  1. 19 CFR 133.22 - Restrictions on importation of articles bearing copying or simulating trademarks.

    Science.gov (United States)

    2010-04-01

    ... shall be detained for 30 days from the date on which the goods are presented for Customs examination, to... counterfeit trademarks. The provisions of paragraph (c)(1) of this section are not applicable to articles bearing counterfeit trademarks at the time of importation (see § 133.26). (e) Release of detained articles...

  2. 31 CFR 538.514 - Certain transactions related to patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... patents, trademarks and copyrights authorized. 538.514 Section 538.514 Money and Finance: Treasury... TREASURY SUDANESE SANCTIONS REGULATIONS Licenses, Authorizations, and Statements of Licensing Policy § 538.514 Certain transactions related to patents, trademarks and copyrights authorized. (a) All of the...

  3. 31 CFR 535.528 - Certain transactions with respect to Iranian patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... Iranian patents, trademarks and copyrights authorized. 535.528 Section 535.528 Money and Finance: Treasury... TREASURY IRANIAN ASSETS CONTROL REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 535.528 Certain transactions with respect to Iranian patents, trademarks and copyrights authorized. (a...

  4. 31 CFR 537.522 - Certain transactions related to patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... patents, trademarks and copyrights authorized. 537.522 Section 537.522 Money and Finance: Treasury... TREASURY BURMESE SANCTIONS REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 537.522 Certain transactions related to patents, trademarks and copyrights authorized. (a) All of the...

  5. 31 CFR 560.509 - Certain transactions related to patents, trademarks and copyrights authorized.

    Science.gov (United States)

    2010-07-01

    ... patents, trademarks and copyrights authorized. 560.509 Section 560.509 Money and Finance: Treasury... TREASURY IRANIAN TRANSACTIONS REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 560.509 Certain transactions related to patents, trademarks and copyrights authorized. (a) All of the...

  6. 31 CFR 500.527 - Certain transactions with respect to United States patents, trademarks, and copyrights.

    Science.gov (United States)

    2010-07-01

    ... United States patents, trademarks, and copyrights. 500.527 Section 500.527 Money and Finance: Treasury... TREASURY FOREIGN ASSETS CONTROL REGULATIONS Licenses, Authorizations and Statements of Licensing Policy § 500.527 Certain transactions with respect to United States patents, trademarks, and copyrights. (a...

  7. Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

    Science.gov (United States)

    Attar, Eyal C; Amrein, Philip C; Fraser, James W; Fathi, Amir T; McAfee, Steven; Wadleigh, Martha; Deangelo, Daniel J; Steensma, David P; Stone, Richard M; Foster, Julia; Neuberg, Donna; Ballen, Karen K

    2013-09-01

    We conducted a phase I dose escalation study to determine the maximal tolerated dose of bortezomib that could be combined with standard dose lenalidomide in patients with MDS or AML. Treatment consisted of bortezomib (IV) on Days 1, 4, 8, and 11 and lenalidomide 10mg daily (PO) days 1-21 in 28 day cycles for up to 9 cycles. 23 patients (14 MDS/CMML, 9 AML) were enrolled. The maximally tested dose of bortezomib, 1.3mg/m(2), was tolerable in this regimen. Responses were seen in patients with MDS and AML. Further testing of this regimen is planned. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

    2011-03-15

    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  9. Neurological monitoring reduces the incidence of bortezomib-induced peripheral neuropathy in multiple myeloma patients.

    Science.gov (United States)

    Velasco, Roser; Petit, Josep; Clapés, Victoria; Verdú, Enric; Navarro, Xavier; Bruna, Jordi

    2010-03-01

    Bortezomib (BTZ) is a proteasome inhibitor approved in the treatment of multiple myeloma (MM). Bortezomib-induced peripheral neuropathy (BIPN) is an unpredictable dose-limiting adverse event in one-third of patients. In the present study, 58 relapsed/refractory MM patients treated with BTZ were analyzed. The study's aim was to compare BIPN incidence and severity between both groups and to identify risk factors of BIPN. Twenty-four MM patients were evaluated by a neurologist periodically during BTZ treatment in order to prevent high-grade BIPN. Thirty-five MM patients previously treated with BTZ were reviewed. Seven (29%) patients in the monitored group and 19 (56%) in the historical cohort developed BIPN (p = 0.044). In the univariate analysis, factors related to BIPN in the whole series were age, number of vincristine and BTZ cycles, lactate dehydrogenase and neurological monitoring. Multivariate analysis revealed that absence of neurological monitoring (Hazard Ratio [HR]: 4.94 IC 95% [1.31-18.68], p = 0.019) and prior treatment with vincristine (HR: 1.34 IC 95% [1.04-1.74], p = 0.026) were associated with greater risk of BIPN. Baseline total neuropathy score-clinical version (TNSc) was a good predictor of BIPN, with higher risk for patients with TNSc >2 (p = 0.038). Neurological monitoring is useful for diminishing BIPN. Neurological monitoring of patients with baseline TNSc >2 should be considered.

  10. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Directory of Open Access Journals (Sweden)

    Eva Szegezdi

    2011-03-01

    Full Text Available Acute myeloid leukemia (AML is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification, which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  11. Update on the optimal use of bortezomib in the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Mohan M

    2017-03-01

    Full Text Available Meera Mohan, Aasiya Matin, Faith E Davies Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA Abstract: The proteasome inhibitor (PI “bortezomib” has now been in routine clinical practice for over a decade. It is now considered an important backbone therapy for all stages of the disease, and data continue to grow to support its use in newly diagnosed patients, relapsed and relapsed/refractory disease, maintenance therapy, high risk, and renal failure. Much has been learnt about the most clinically effective way of delivering therapy, with patients often benefiting more from a triplet bortezomib combination compared to a doublet combination. It is well tolerated and can be administered in the outpatient setting with manageable toxicity. The key to good results is managing side effects so that patients remain on therapy with minimal interruptions. Therefore, proactive management of peripheral neuropathy and thrombocytopenia is advised using dose delay and reduction strategies. The recent introduction of second- and third-generation PIs with different chemical and biological properties has resulted in a plethora of new clinical studies and has confirmed the ongoing role of this class of drugs in future myeloma therapy. Keywords: multiple myeloma, proteasome inhibitor, bortezomib, treatment

  12. Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

    DEFF Research Database (Denmark)

    Sezer, Orhan; Beksac, Meral; Hajek, Roman

    2017-01-01

    This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycl...

  13. Final Results of a Phase 1 Study of Vorinostat, Pegylated Liposomal Doxorubicin, and Bortezomib in Relapsed or Refractory Multiple Myeloma.

    Science.gov (United States)

    Voorhees, Peter M; Gasparetto, Cristina; Moore, Dominic T; Winans, Diane; Orlowski, Robert Z; Hurd, David D

    2017-07-01

    Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma (MM). We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory MM. Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14. The maximum tolerated dose of vorinostat was 400 mg on days 4 to 11. Neutropenia and thrombocytopenia attributable to protocol therapy were seen in 59% and 94% of patients, of which 37% and 47% were of grade 3 or higher severity, respectively. Constitutional and gastrointestinal adverse events of all grades were common, the majority of which were less than grade 3 in severity. The overall response rate (partial response rate or better) was 65% and the clinical benefit rate (minimal response rate or better) 74%. The overall response rate was 83%, 71%, and 45% for patients with bortezomib-naive, -sensitive, and -refractory MM, respectively. The median progression-free survival was 13.9 months and the 3-year overall survival 77%. Whole blood proteasome activity assays demonstrated a potential impact of vorinostat on the chymotryptic-like activity of the proteasome. Further evaluation of PLD, bortezomib, and deacetylase inhibitor combinations is warranted, with special attention directed toward strategies to improve tolerability. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Development of the SEA Corporation Powergrid{trademark} photovoltaic concentrator

    Energy Technology Data Exchange (ETDEWEB)

    Kaminar, N.; Curchod, D.; Daroczi, S.; Walpert, M.; Sahagian, J.; Pepper, J. [Photovoltaics International, LLC, Sunnyvale, CA (United States)

    1998-03-01

    This report covers the three phase effort to bring the SEA Corporation`s Powergrid{trademark} from the concept stage to pilot production. The three phases of this contract covered component development, prototype module development, and pilot line production. The Powergrid is a photovoltaic concentrator that generates direct current electricity directly from sunlight using a linear Fresnel lens. Analysis has shown that the Powergrid has the potential to be very low cost in volume production. Before the start of the project, only proof of concept demonstrations of the components had been completed. During the project, SEA Corporation developed a low cost extruded Fresnel lens, a low cost receiver assembly using one sun type cells, a low cost plastic module housing, a single axis tracking system and frame structure, and pilot production equipment and techniques. In addition, an 800 kW/yr pilot production rate was demonstrated and two 40 kW systems were manufactured and installed.

  15. ReflectoActive(trademark) Seals for Materials Control and Accountability

    International Nuclear Information System (INIS)

    Richardson, G.D.; Younkin, J.R.; Bell, Z.W.

    2002-01-01

    The ReflectoActive(trademark) Seals system, a continuously monitored fiber optic, active seal technology, provides real-time tamper indication for large arrays of storage containers. The system includes a PC running the RFAS software, an Immediate Detection Unit (IDU), an Optical Time Domain Reflectometer (OTDR), links of fiber optic cable, and the methods and devices used to attach the fiber optic cable to the containers. When a breach on any of the attached fiber optic cable loops occurs, the IDU immediately signals the connected computer to control the operations of an OTDR to seek the breach location. The ReflectoActive(trademark) Seals System can be adapted for various types of container closure designs and implemented in almost any container configuration. This automatic protection of valued assets can significantly decrease the time and money required for surveillance. The RFAS software is the multi-threaded, client-server application that monitors and controls the components of the system. The software administers the security measures such as a two-person rule as well as continuous event logging. Additionally the software's architecture provides a secure method by which local or remote clients monitor the system and perform administrative tasks. These features provide the user with a robust system to meet today's material control and accountability needs. A brief overview of the hardware, and different hardware configurations will be given. The architecture of the system software, and its benefits will then be discussed. Finally, the features to be implemented in future versions of the system will be presented

  16. A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

    Science.gov (United States)

    Shah, Manish A; Power, Derek G; Kindler, Hedy L; Holen, Kyle D; Kemeny, Margaret M; Ilson, David H; Tang, Laura; Capanu, Marinela; Wright, John J; Kelsen, David P

    2011-12-01

    The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.

  17. Role of combination bortezomib and pegylated liposomal doxorubicin in the management of relapsed and/or refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    Jatin J Shah

    2009-01-01

    Full Text Available Jatin J Shah1, Robert Z Orlowski1,2, Sheeba K Thomas11Departments of Lymphoma/Myeloma; 2Experimental Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: The first in class proteasome inhibitor bortezomib (B received its initial regulatory approval for therapy of patients with multiple myeloma (MM in the relapsed/refractory setting. Modulation of proteasome function, however, is also a rational strategy for chemosensitization, and a variety of agents have shown synergistic activity with bortezomib pre-clinically, including anthracyclines. This formed the basis for evaluation of a regimen of bortezomib with pegylated liposomal doxorubicin (PLD. PLD+B, in a phase I study, induced a predictable and manageable toxicity profi le, and showed encouraging anti-MM activity. In a recent international, randomized phase III trial, PLD+B demonstrated a superior overall response rate and response quality compared to bortezomib alone, as well as a longer time to progression, duration of response, progression-free survival, and overall survival. Sub-analyses revealed benefits in almost all clinically relevant subgroups, including several which would be considered to have high-risk disease. These findings have led to the establishment of the PLD+B regimen as one of the standards of care for patients with relapsed and/or refractory myeloma. Efforts are now underway to build on this combination further by adding other active anti-myeloma agents. In this review, we will discuss the role of PLD+B as an important addition to our therapeutic armamentarium for patients with MM.Keywords: multiple myeloma, relapsed/refractory, pegylated liposomal doxorubicin, bortezomib, Doxil®, Velcade®

  18. Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yi Xiao

    Full Text Available BACKGROUND: We conducted a systematic review and meta-analysis to clarify the incidence and risk of cardiotoxicity associated with bortezomib in cancer patients. METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to July 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating bortezomib in cancer patients with adequate data on cardiotoxicity. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR and 95% confidence intervals (CIs by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 5718 patients with a variety of malignancies from 25 clinical trials were included in our analysis. The incidence of all-grade and high-grade cardiotoxicity associated with bortezomib was 3.8% (95%CI: 2.6-5.6% and 2.3% (1.6-3.5%, with a mortality of 3.0% (1.4-6.5%. Patients treated with bortezomib did not significantly increase the risk of all-grade (OR 1.15, 95%CI: 0.82-1.62, p=0.41 and high-grade (OR 1.13, 95%CI: 0.58-2.24, p=0.72 cardiotoxicity compared with patients treated with control medication. Sub-group analysis showed that the incidence of cardiotoxicity varied with tumor types, treatment regimens and phases of trials. No evidence of publication bias was observed. CONCLUSIONS: The use of bortezomib does not significantly increase the risk of cardiotoxicity compared to control patients. Further studies are recommended to investigate this association and risk differences among different tumor types, treatment regimens and phases of trials.

  19. A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors.

    Science.gov (United States)

    Deming, Dustin A; Ninan, Jacob; Bailey, Howard H; Kolesar, Jill M; Eickhoff, Jens; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Alberti, Dona; Marnocha, Rebecca; Espinoza-Delgado, Igor; Wright, John; Wilding, George; Schelman, William R

    2014-04-01

    Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib. Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11. 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST. The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.

  20. Drying of sewage sludge using the ECACTHERM {sup trademark} process; Trocknung von Abwasserschlaemmen mit dem ECACTHERM {sup trademark} Verfahren

    Energy Technology Data Exchange (ETDEWEB)

    Gerl, S. [Maschinenfabrik Gustav Eirich GmbH und Co KG, Hardheim (Germany)

    2003-07-01

    This is an established process in many fields of industry. For drying, superheated water vapour is introduced into a mechanically fluidized bed. The granulated end products are cooled in a vacuum using the cold generated by evaporation cooling. In partial vacuum and in a closed-loop process, drying and granulation take place in inert conditions, without unpleasant smell and with minimum energy consumption. (orig.) [German] Der EVACTHERM {sup trademark} Vakuumheissdampftrocknungsprozess in einem Eirich Mischreaktor ist seit vielen Jahren in den verschiedensten Industriebereichen zur Schlammaufbereitung erfolgreich im Einsatz. Die Trocknung erfolgt durch Einleitung von ueberhitztem Wasserdampf in ein mechanisch erzeugtes Wirbelbett. Die Kuehlung des granulierten Endproduktes wird durch Anlegen von Vakuum unter Ausnutzung der Verdampfungskuehlung erzielt. Durch die Aufbereitung im leichten Unterdruck und dem Betrieb in geschlossener Kreislauffuehrung mit ueberhitztem Dampf, erfolgt die Trocknung und Granulierung unter inerten Bedingungen, ohne Geruchsemissionen und bei minimalem Energieverbrauch. (orig.)

  1. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients...... received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also...... studied in vitro. RESULTS: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro...

  2. Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/GMMG-HD4 Trial

    NARCIS (Netherlands)

    Sonneveld, Pieter; Schmidt-Wolf, Ingo G. H.; van der Holt, Bronno; el Jarari, Laila; Bertsch, Uta; Salwender, Hans; Zweegman, Sonja; Vellenga, Edo; Broyl, Annemiek; Blau, Igor W.; Weisel, Katja C.; Wittebol, Shulamiet; Bos, Gerard M. J.; Stevens-Kroef, Marian; Scheid, Christof; Pfreundschuh, Michael; Hose, Dirk; Jauch, Anna; van der Velde, Helgi; Raymakers, Reinier; Schaafsma, Martijn R.; Kersten, Marie-Jose; van Marwijk-Kooy, Marinus; Duehrsen, Ulrich; Lindemann, Walter; Wijermans, Pierre W.; Lokhorst, Henk M.; Goldschmidt, Hartmut M.

    2012-01-01

    Purpose We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and Methods In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine,

  3. Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma : Results of the Randomized Phase III HOVON-65/GMMG-HD4 Trial

    NARCIS (Netherlands)

    Sonneveld, Pieter; Schmidt-Wolf, Ingo G. H.; van der Holt, Bronno; el Jarari, Laila; Bertsch, Uta; Salwender, Hans; Zweegman, Sonja; Vellenga, Edo; Broyl, Annemiek; Blau, Igor W.; Weisel, Katja C.; Wittebol, Shulamiet; Bos, Gerard M. J.; Stevens-Kroef, Marian; Scheid, Christof; Pfreundschuh, Michael; Hose, Dirk; Jauch, Anna; van der Velde, Helgi; Raymakers, Reinier; Schaafsma, Martijn R.; Kersten, Marie-Jose; van Marwijk-Kooy, Marinus; Duehrsen, Ulrich; Lindemann, Walter; Wijermans, Pierre W.; Lokhorst, Henk M.; Goldschmidt, Hartmut M.

    2012-01-01

    Purpose We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and Methods In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine,

  4. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

    DEFF Research Database (Denmark)

    San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

    2014-01-01

    . Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination...... group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p... [60·7%, 95% CI 55·7-65·6] for panobinostat vs 208 [54·6%, 49·4-59·7] for placebo; p=0·09); however, the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group (107 [27·6%, 95% CI 23·2-32·4] vs 60 [15·7%, 12...

  5. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  6. Real-time billboard trademark detection and recognition in sports video

    Science.gov (United States)

    Bu, Jiang; Lao, Song-Yan; Bai, Liang

    2013-03-01

    Nowadays, different applications like automatic video indexing, keyword based video search and TV commercials can be developed by detecting and recognizing the billboard trademark. We propose a hierarchical solution for real-time billboard trademark recognition in various sports video, billboard frames are detected in the first level, fuzzy decision tree with easily-computing features are employed to accelerate the process, while in the second level, color and regional SIFT features are combined for the first time to describe the appearance of trademarks, and the shared nearest neighbor (SNN) clustering with x2 distance is utilized instead of traditional K-means clustering to construct the SIFT vocabulary, at last, Latent Semantic Analysis (LSA) based SIFT vocabulary matching is performed on the template trademark and the candidate regions in billboard frame. The preliminary experiments demonstrate the effectiveness of the hierarchical solution, and real time constraints are also met by our solution.

  7. Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in Echinococcus granulosus larval stage

    Science.gov (United States)

    Nicolao, María Celeste; Loos, Julia A.; Rodriguez Rodrigues, Christian; Beas, Viviana

    2017-01-01

    Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P Echinococcus cell viability, we evaluated the efficacy of Bz in combination with rapamycin and a synergistic cytotoxic effect on protoscolex viability was observed when both drugs were used together. In conclusion, our findings demonstrated that Bz induced endoplasmic reticulum stress, autophagy and subsequent death allowing to identify unstudied parasite-host pathways that could provide a new insight for control of parasitic diseases. PMID:28817601

  8. Treatment of idiopathic light chain deposition disease: complete remission with bortezomib and dexamethasone

    Directory of Open Access Journals (Sweden)

    João Tadeu Damian Souto Filho

    Full Text Available Abstract Light chain deposition disease (LCDD is a rare clinical entity characterized by the deposition of light chain immunoglobulins in different tissues and primarily affects the kidneys, followed by the liver and heart. This disease often manifests as nephrotic syndrome with marked proteinuria and rapid deterioration of renal function. More than 50% of cases are secondary to multiple myeloma or other lymphoproliferative diseases, with a well-established treatment aimed at controlling the underlying disease. In rare cases, there is no detection of an associated hematological disease, referred to as idiopathic LCDD. In these cases, there is no evidence-based consensus on the therapeutic approach, and management is based on the clinical experience of reported cases. Here we report a case of idiopathic LCDD treated with bortezomib and dexamethasone with complete hematologic responses, significant reduction of proteinuria, and improved renal function.

  9. Pilot-scale of MecTool trademark: A novel approach to in-situ remediation

    International Nuclear Information System (INIS)

    Hemmings, R.; Hoeffner, S.; Schafer, J.; Kappler, R.

    1994-01-01

    The MecTool trademark is an in situ mixing and fluid delivery system consisting of a 4 to 14 feet in diameter boring/mixing tool, a hollow stem kelly bar with an integral fluid delivery system, high torque earth-drilling equipment, an off-gas collection system, and computerized control and monitoring. The MecTool trademark has been used in several field treatments. demonstrations and studies. To further the technology and to provide a technical basis for the MecTool trademark treatment system, a mini-MecTool trademark was used to evaluate pilot-scale performance. The mini-MecTool trademark is a miniature version of the field unit and consists of a hollow Kelly bar and a 10 inch diameter auger with injection ports. A sandy clay soil representing a typical unsaturated zone soil was spiked with contaminants of interest (organics, metals and radionuclides). The spiked soil was treated with the mini-MecTool trademark unit using hot air stripping for removal of volatile organics, stabilization to reduce the volatilization of organics and to fix metals and radionuclides, peroxide injection for wet oxidation of the organics and bioremediation to degrade the volatile organics. For comparison, laboratory controls representing ideal treatment conditions were also performed for these same four technologies. In each case, the mini-MecTool trademark pilot-scale test was compared to the laboratory control sample treated under optimum conditions. The MecTool trademark in-situ methodology showed good promise for the range of contaminants considered

  10. Physicochemical characterization of different trademarks of compound Yerba Maté and their herbs

    OpenAIRE

    Scipioni,Griselda Patricia; Ferreyra,Darío Jorge; Schmalko,Miguel Eduardo

    2007-01-01

    The objectives of this study were to evaluate the physicochemical characteristics of the main herbs used in the mixture of yerba maté with other aromatic herbs and the characterization of the trademarks of compound yerba maté. Moisture, water extract, total ash, acid-insoluble ash and caffeine concentration were determined. Results showed higher values of moisture content, total and aci-insoluble ash and lower water extracts in the herbs. Determinations were carried out in nine trademarks of ...

  11. The Effects of the Coffee Trademarking Initiative and Starbucks Publicity on Export Prices of Ethiopian Coffee

    OpenAIRE

    Aslihan Arslan; Christopher P. Reicher

    2011-01-01

    The Ethiopian government initiated the Ethiopian Coffee Trademarking and Licensing Initiative in 2004 for three coffee origins: Sidama, Yirgacheffe and Harar. Following a court case between Starbucks and the Ethiopian government regarding the trademarking of Sidamo, Ethiopian government engaged in a public relations campaign to raise awareness for the Initiative, which was widely publicised in the international media especially after Oxfam organised a public campaign. This paper evaluates the...

  12. Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells.

    Science.gov (United States)

    Tibullo, Daniele; Di Rosa, Michelino; Giallongo, Cesarina; La Cava, Piera; Parrinello, Nunziatina L; Romano, Alessandra; Conticello, Concetta; Brundo, Maria V; Saccone, Salvatore; Malaguarnera, Lucia; Di Raimondo, Francesco

    2015-01-01

    Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients. It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases chitotriosidase (CHIT1) and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib's concentration (2.5 and 5 nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to bortezomib (BO) was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP, and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disk assay resorption pits. Silencing chitinase proteins in U266 cell line with specific small interfering RNA, resulted in pits number reduction on dentine disks. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients.

  13. SENTINEL trademark technical basis report for Limerick. Final report

    International Nuclear Information System (INIS)

    Burns, E.T.; Lee, L.K.; Mitman, J.T.; Vanover, D.E.; Wilson, D.K.

    1997-12-01

    PECO Energy in cooperation with the Electric Power Research Institute (EPRI) installed the SENTINEL trademark software at its Limerick Generating Station. This software incorporates models of the safety and support systems which are used to display the defense in depth present in the plant and a quantitative assessment of the plant risks during proposed on-line maintenance. During the past year, PECO Energy personnel have used this display to evaluate the safety of proposed on-line maintenance schedules. The report describes the motivation for and the development of the SENTINEL software. It describes the generation of Safety Function Assessment Trees and Plant Transient Assessment Trees and their use in evaluating the level of defense-in-depth of key plant safety functions and the susceptibility of the plant to critical transient events. Their results are displayed by color indicators ranging from green, through yellow and orange to red to show increasingly hazardous conditions. The report describes the use of the Limerick Probabilistic Safety Assessment within the SENTINEL code to calculate an instantaneous core damage frequency and the criteria by which this frequency is translated to a color indicator. Finally, the report describes the Performance Criteria Assessment which tracks and trends system/train unavailability to document conformance to the requirements of the Maintenance Rule

  14. Quantum-CEP trademark for mixed waste processing

    International Nuclear Information System (INIS)

    Nahass, P.; Sekula-Moise, P.A.; Chanenchuk, C.A.

    1994-01-01

    No commercially available technology exists to effectively treat the hundreds of thousands of tons of mixed waste stored and generated in the United States and worldwide. Catalytic Extraction Processing (CEP) is an innovative flexible recycling technology which has inherent advantages for processing mixed wastes in a wide variety of chemical and physical forms. CEP uses a molten metal bath to completely dissociate feeds and recombine them with selected reactants to form useful products. Dissolved carbon in the metal bath creates a reducing atmosphere, readily converting hydrocarbons to synthesis gas, metals to alloys in their reduced state, and inorganics to an engineered ceramic phase. Process conditions can be manipulated to strongly favor partitioning of select radionuclides to a nonleachable vitreous phase, ready for final form disposal. Molten Metal Technology has adapted its CEP technology for radioactive processing and has delivered Quantum-CEP trademark units to customers for demonstration of mixed waste processing leading to commercial scale installations for reducing both private and government inventories. Agreements have also been reached to build commercial CEP facilities to recycle hazardous and industrial wastes

  15. Diphonix trademark Resin: A review of its properties and applications

    International Nuclear Information System (INIS)

    Chiarizia, R.; Horwitz, E.P.; Alexandratos, S.D.

    1995-01-01

    The recently developed Diphonix trademark resin is a new multifunctional chelating ion exchange resin containing seminally substituted diphosphonic acid ligands chemically bonded to a styrene-based polymeric matrix. Diphonix can be regarded as a dual mechanism polymer, with a sulfonic acid cation exchange group allowing for rapid access, mostly non-specific, of ions into the polymeric network, and the diphosphonic acid group responsible for specificity (recognition) for a number of metal cations. The Diphonix resin exhibits an extraordinarily strong affinity for actinides, especially in the tetra- and hexavalent oxidation states. It has potential applications in TRU and mixed waste treatment and characterization, and in the development of new procedures for rapid actinide preconcentration and separation from environmental samples. Metal uptake studies have been extended to alkaline earth cations, to transition and post transition metal species, and to metal sorption from neutral or near neutral solutions. Also the kinetic behavior of the resin has been investigated in detail. Influence of the most commonly occurring matrix constituents (Na, Ca, Al, Fe, hydrofluoric, sulfuric, oxalic and phosphoric acids) on the uptake of actinide ions has been measured. This review paper summarizes the most important results studies on the Diphonix resin and gives an overview of the applications already in existence or under development in the fields of mixed waste treatment, actinide separation procedures, treatment of radwaste from nuclear power plants, and removal of iron from copper electrowinning solutions

  16. The Technology Information Environment with Industry{trademark} system description

    Energy Technology Data Exchange (ETDEWEB)

    Detry, R.; Machin, G. [Sandia National Labs., Albuquerque, NM (United States). Scientific Computing Systems Dept.

    1996-03-01

    The Technology Information Environment with Industry (TIE-In{trademark}) provides users with controlled access to distributed laboratory resources that are packaged in intelligent user interfaces. These interfaces help users access resources without requiring the user to have technical or computer expertise. TIE-In utilizes existing, proven technologies such as the Kerberos authentication system, X-Windows, and UNIX sockets. A Front End System (FES) authenticates users and allows them to register for resources and subsequently access them. The FES also stores status and accounting information, and provides an automated method for the resource owners to recover costs from users. The resources available through TIE-In are typically laboratory-developed applications that are used to help design, analyze, and test components in the nation`s nuclear stockpile. Many of these applications can also be used by US companies for non-weapons-related work. TIE-In allows these industry partners to obtain laboratory-developed technical solutions without requiring them to duplicate the technical resources (people, hardware, and software) at Sandia.

  17. Pipe Explorer{trademark} surveying system. Innovative technology summary report

    Energy Technology Data Exchange (ETDEWEB)

    1999-06-01

    The US Department of Energy`s (DOE) Chicago Operations Office and the DOE`s Federal Energy Technology Center (FETC) developed a Large Scale Demonstration Project (LSDP) at the Chicago Pile-5 Research Reactor (CP-5) at Argonne National Laboratory-East (ANL). The objective of the LSDP is to demonstrate potentially beneficial decontamination and decommissioning (D and D) technologies in comparison with current baseline technologies. The Pipe Explorer{trademark} system was developed by Science and Engineering Associates, Inc. (SEA), Albuquerque, NM as a deployment method for transporting a variety of survey tools into pipes and ducts. Tools available for use with the system include alpha, beta and gamma radiation detectors; video cameras; and pipe locator beacons. Different versions of this technology have been demonstrated at three other sites; results of these demonstrations are provided in an earlier Innovative Technology Summary Report. As part of a D and D project, characterization radiological contamination inside piping systems is necessary before pipes can be recycled, remediated or disposed. This is usually done manually by surveying over the outside of the piping only, with limited effectiveness and risk of worker exposure. The pipe must be accessible to workers, and embedded pipes in concrete or in the ground would have to be excavated at high cost and risk of exposure to workers. The advantage of the Pipe Explorer is its ability to perform in-situ characterization of pipe internals.

  18. Subsurface barrier validation with the SEAtrace{trademark} system

    Energy Technology Data Exchange (ETDEWEB)

    Sandra Dalvit Dunn; William Lowry; Veraun Chipman

    1999-09-01

    Under contract to the Department of Energy, Science and Engineering Associates has completed development and testing of a subsurface barrier verification and monitoring system. This system, called SEAtrace{trademark}, is able to locate and size leaks with a high degree of accuracy in subsurface barriers that are emplaced in an unsaturated medium. It uses gaseous tracer injection, in-field real-time monitoring, and real time data analysis to evaluate barrier integrity. The approach is: Conservative as it measures vapor leaks in a containment system whose greatest risk is posed by liquid leaks; Applicable to any impermeable type of barrier emplacement technology in the unsaturated zone; Inexpensive as it uses readily available, non-toxic, nonhazardous gaseous tracers, does not require an inordinately large number of sampling points, and injection and sampling points can be emplaced by direct push techniques; Capable of assessing not only a barrier's initial integrity, but can also provide long-term monitoring. To date, six demonstrations of the system have been completed. Results from two of the demonstrations are detailed in this report. They include the final developmental demonstration of the SEAtrace system and a comparison demonstration of two tracer based verification technologies. The final developmental demonstration of SEAtrace was completed at a naval facility in Brunswick, Maine. The demonstration was funded solely by the DOE and was performed in cooperation with the US Navy, the Environmental Protection Agency, and the Maine Department of Environmental Protection.

  19. The AMTEX Partnership{trademark}: Creating and implementing a vision

    Energy Technology Data Exchange (ETDEWEB)

    Liebetrau, S.F.; Erickson, M.D.; Lemon, D.K.

    1993-12-01

    The vision and creativity of the multilaboratory team nominated for a special award resulted in the AMTEX Partnership{trademark}, a pace-setting agreement between US Department of Energy national laboratories and the US textile industry. The AMTEX Partnership is a role model for America to follow that brings the resources of government to bear on industrial needs while preserving the American values of free enterprise and fairness of opportunity. Together, the nominees created an important vision of the future. They capitalized on a government-sponsored workshop that provided an opportunity for industry to hear about laboratory capabilities. At the workshop, they attracted the attention of the integrated textile industry, a major segment of US industry whose economic future is very much at risk. They listened to the industry representatives, grasped the scope and implications of the industry`s needs - and recognized the potential for large-scale collaboration. In keeping with the scale of this prospect, they guided nine national laboratories from traditional ways of technology transfer into a cooperative venture with an entire vertically integrated industry.

  20. Savings potential of ENERGY STAR (registered trademark) voluntary labeling programs

    International Nuclear Information System (INIS)

    Webber, Carrie A.; Brown, Richard E.

    1998-01-01

    In 1993 the U.S. Environmental Protection Agency (EPA) introduced ENERGY STAR (registered trademark), a voluntary labeling program designed to identify and promote energy-efficient products. Since then EPA, now in partnership with the U.S. Department of Energy (DOE), has introduced programs for more than twenty products, spanning office equipment, residential heating and cooling equipment, new homes, commercial and residential lighting, home electronics, and major appliances. We present potential energy, dollar and carbon savings forecasts for these programs for the period 1998 to 2010. Our target market penetration case represents our best estimate of future ENERGY STAR savings. It is based on realistic market penetration goals for each of the products. We also provide results under the assumption of 100% market penetration; that is, we assume that all purchasers buy ENERGY STAR-compliant products instead of standard efficiency products throughout the analysis period. Finally, we assess the sensitivity of our target penetration case forecasts to greater or lesser marketing success by EPA and DOE, lower-than-expected future energy prices, and higher or lower rates of carbon emission by electricity generators. The potential savings of ENERGY STAR are substantial. If all purchasers chose Energy Star-compliant products instead of standard efficiency products over the next 15 years, they would save more than$100 billion on their energy bills during those 15 years. (Bill savings are in 1995 dollars, discounted at a 4% real discount rate.)

  1. Flow and pressures networks simulation under VisSim trademark graphic interphase

    International Nuclear Information System (INIS)

    Roldan-Villasana, E.J.; Porras-Loaiza, G.L.; Jimenez-Sauma, B.; Berdon-Alarcon, R.

    1996-01-01

    In this work, a graphic interphase to facilitate the interaction between the user and a flow and pressure network (FPN) model is presented. The graphic interphase was designed using the VisSim trademark commercial software (VisSim, 1994) which is a visual programming mathematical tool that allows direct simulation from graphics constructed using block diagrams. VisSim trademark was not used to solve the FPN but an external program (solver) was designed ex professo. The reason for this is that VisSim trademark is not able to work with a model whose structure may vary in size and topology. Thus, VisSim trademark was used as a graphic interphase exclusively. The main problem was to interpret the flow diagram (which shows the topology of the system) to feed the solver. This interpretation was made with a preprocessor which reads the VisSim trademark data file (·VSM file) containing the information of all the VisSim trademark configuration, extracts the information of the topology, and feeds the solver

  2. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

    DEFF Research Database (Denmark)

    Kumar, S K; Lee, JH; Lahuerta, J J

    2012-01-01

    with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis...... was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least...

  3. HDAC Inhibitor L-Carnitine and Proteasome Inhibitor Bortezomib Synergistically Exert Anti-Tumor Activity In Vitro and In Vivo

    OpenAIRE

    Huang, Hongbiao; Liu, Ningning; Yang, Changshan; Liao, Siyan; Guo, Haiping; Zhao, Kai; Li, Xiaofen; Liu, Shouting; Guan, Lixia; Liu, Chunjiao; Xu, Li; Zhang, Change; Song, Wenbin; Li, Bing; Tang, Ping

    2012-01-01

    Combinations of proteasome inhibitors and histone deacetylases (HDAC) inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC) is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel) was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by fl...

  4. Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

    LENUS (Irish Health Repository)

    Ward, F

    2012-05-01

    We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

  5. How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study.

    Science.gov (United States)

    Huang, Bin-Tao; Tan, Yan; Zhao, Wei-Hong; Zeng, Qing-Chun; Li, Bing-Sheng; Chen, Rui-Lin

    2014-02-01

    This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM). Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65-89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52). Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P CBd group (P CBd arm (39.2 vs. 13.1 %, P CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.

  6. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  7. The proteasome inhibitor bortezomib induces an inhibitory chromatin environment at a distal enhancer of the estrogen receptor-α gene.

    Directory of Open Access Journals (Sweden)

    Ginny L Powers

    Full Text Available Expression of the estrogen receptor-α (ERα gene, ESR1, is a clinical biomarker used to predict therapeutic outcome of breast cancer. Hence, there is significant interest in understanding the mechanisms regulating ESR1 gene expression. Proteasome activity is increased in cancer and we previously showed that proteasome inhibition leads to loss of ESR1 gene expression in breast cancer cells. Expression of ESR1 mRNA in breast cancer cells is controlled predominantly through a proximal promoter within ∼400 base pair (bp of the transcription start site (TSS. Here, we show that loss of ESR1 gene expression induced by the proteasome inhibitor bortezomib is associated with inactivation of a distal enhancer located 150 kilobases (kb from the TSS. Chromatin immunoprecipitation assays reveal several bortezomib-induced changes at the distal site including decreased occupancy of three critical transcription factors, GATA3, FOXA1, and AP2γ. Bortezomib treatment also resulted in decreased histone H3 and H4 acetylation and decreased occupancy of histone acetyltransferase, p300. These data suggest a mechanism to explain proteasome inhibitor-induced loss of ESR1 mRNA expression that highlights the importance of the chromatin environment at the -150 kb distal enhancer in regulation of basal expression of ESR1 in breast cancer cells.

  8. Bortezomib enhances expression of effector molecules in anti-tumor CD8+ T lymphocytes by promoting Notch-nuclear factor-κB crosstalk.

    Science.gov (United States)

    Thounaojam, Menaka C; Dudimah, Duafalia F; Pellom, Samuel T; Uzhachenko, Roman V; Carbone, David P; Dikov, Mikhail M; Shanker, Anil

    2015-10-20

    The immunosuppressive tumor microenvironment usurps host antitumor immunity by multiple mechanisms including interference with the Notch system, which is important for various metazoan cell fate decisions and hematopoietic cell differentiation and function. We observed that treatment with the proteasome inhibitor bortezomib in mice bearing various solid tumors resulted in an upregulated expression of various Notch signaling components in lymphoid tissues, thereby increasing CD8+T-lymphocyte IFNγ secretion and expression of effector molecules, perforin and granzyme B, as well as the T-box transcription factor eomesodermin. Bortezomib also neutralized TGFβ-mediated suppression of IFNγ and granzyme B expression in activated CD8+T-cells. Of note, bortezomib reversed tumor-induced downregulation of Notch receptors, Notch1 and Notch2, as well as increased the levels of cleaved Notch intracellular domain (NICD) and downstream targets Hes1 and Hey1 in tumor-draining CD8+T-cells. Moreover, bortezomib promoted CD8+T-cell nuclear factor-κB (NFκB) activity by increasing the total and phosphorylated levels of the IκB kinase and IκBα as well as the cytoplasmic and nuclear levels of phosphorylated p65. Even when we blocked NFκB activity by Bay-11-7082, or NICD cleavage by γ-secretase inhibitor, bortezomib significantly increased expression of Notch Hes1 and Hey1 genes as well as perforin, granzyme B and eomesodermin in activated CD8+T-cells. Data suggest that bortezomib can rescue tumor-induced dysfunction of CD8+T-cells by its intrinsic stimulatory effects promoting NICD-NFκB crosstalk. These findings provide novel insights on using bortezomib not only as an agent to sensitize tumors to cell death but also to provide lymphocyte-stimulatory effects, thereby overcoming immunosuppressive actions of tumor on anti-tumor T-cell functions.

  9. The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78.

    Science.gov (United States)

    Roué, Gaël; Pérez-Galán, Patricia; Mozos, Ana; López-Guerra, Mónica; Xargay-Torrent, Sílvia; Rosich, Laia; Saborit-Villarroya, Ifigènia; Normant, Emmanuel; Campo, Elias; Colomer, Dolors

    2011-01-27

    Despite the promising introduction of the proteasome inhibitor bortezomib in the treatment of mantle cell lymphoma (MCL), not all patients respond, and resistance often appears after initial treatment. By analyzing a set of 18 MCL samples, including cell lines with constitutive or induced resistance to bortezomib, we found a high correlation between loss of sensitivity to the proteasome inhibitor and up-regulation of the prosurvival chaperone BiP/Grp78. BiP/Grp78 stabilization was ensured at a posttranscriptional level by an increase in the chaperoning activity of heat shock protein of 90 kDa (Hsp90). In bortezomib-resistant cells, both BiP/Grp78 knockdown and cell pretreatment with the Hsp90 inhibitor of the ansamycin class, IPI-504, led to synergistic induction of apoptotic cell death when combined with bortezomib. Cell exposure to the IPI-504-bortezomib combination provoked the dissociation of Hsp90/BiP complexes, leading to BiP/Grp78 depletion, inhibition of unfolded protein response, and promotion of NOXA-mediated mitochondrial depolarization. The IPI-504-bortezomib combination also prevented BiP/Grp78 accumulation, thereby promoting apoptosis and inhibiting the growth of bortezomib-resistant tumors in a mouse model of MCL xenotransplantation. These results suggest that targeting unfolded protein response activation by the inhibition of Hsp90 may be an attractive model for the design of a new bortezomib-based combination therapy for MCL.

  10. Bluetooth(Registered Trademark) Heart Rate Monitors for Spaceflight

    Science.gov (United States)

    Buxton, Roxanne E.; West, Michael R.; Kalogera, Kent L.; Hanson, Andrea M.

    2016-01-01

    ISS Bluetooth validation study, because it simultaneously transmits Magnetic Pulse which is integrated with existing exercise hardware on ISS. The simultaneous data streams allow for beat to beat comparison between the current ISS standard and CS2.Upon Bluetooth(Registered Trademark) validation aboard ISS, down select of a new BT_HRM for operational use will be made.

  11. “Mark my words” - Trademarks and Fundamental Rights in the EU

    DEFF Research Database (Denmark)

    Schovsbo, Jens Hemmingsen

    2017-01-01

    . It is concluded that even though the constitutionalization is not going to revolutionize EU trademark law, it will require courts to consider in a more pronounced way the interests of users’ of trade marks (such as artists or commercial users) vis-à-vis trade mark holders’ interests. This in turn may affect...... of ‘constitiutionalization’ in EU law whereby courts increasingly rely on fundamental rights when they interpret the rules of IPR. After a presentation of the historical and legislative background for the changes and the related development in copyright law, the likely impact of the new trademark rules is discussed...... the way court interpret trade mark law and in particular give more room to the limitations and exceptions. The effects of such a development may be to limit the ability of trademark holders to push exclusivity in ways that harm cultural development, public debate and fair competition....

  12. Houdini{trademark}: Reconfigurable in-tank mobile robot. Final report, June 1995--January 1997

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, B.; Slifko, A.

    1998-12-31

    This report details the development of a reconfigurable in-tank robotic cleanup system called Houdini{trademark}. Driven by the general need to develop equipment for the removal of radioactive waste from hundreds of DOE waste storage tanks and the specific needs of DOE sites such as Oak Ridge National Laboratory and Fernald, Houdini{trademark} represents one of the possible tools that can be used to mobilize and retrieve this waste material for complete remediation. Houdini{trademark} is a hydraulically powered, track driven, mobile work vehicle with a collapsible frame designed to enter underground or above ground waste tanks through existing 24 inch riser openings. After the vehicle has entered the waste tank, it unfolds and lands on the waste surface or tank floor to become a remotely operated mini-bulldozer. Houdini{trademark} utilizes a vehicle mounted plow blade and 6-DOF manipulator to mobilize waste and carry other tooling such as sluicing pumps, excavation buckets, and hydraulic shears. The complete Houdini{trademark} system consists of the tracked vehicle and other support equipment (e.g., control console, deployment system, hydraulic power supply, and controller) necessary to deploy and remotely operate this system at any DOE site. Inside the storage tanks, the system is capable of performing heel removal, waste mobilization, waste size reduction, and other tank waste retrieval and decommissioning tasks. The first Houdini{trademark} system was delivered on September 24, 1996 to Oak Ridge National Laboratory (ORNL). The system acceptance test was successfully performed at a cold test facility at ORNL. After completion of the cold test program and the training of site personnel, ORNL will deploy the system for clean-up and remediation of the Gunite storage tanks.

  13. SOx-NOx-Rox Box{trademark} flue gas clean-up demonstration. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    The SNRB{trademark} Flue Gas Cleanup Demonstration Project was cooperatively funded by the U.S. Department of Energy (DOE), the Ohio Coal Development Office (OCDO), B&W, the Electric Power Research Institute (EPRI), Ohio Edison, Norton Chemical Process Products Company and the 3M Company. The SNRB{trademark} technology evolved from the bench and laboratory pilot scale to be successfully demonstrated at the 5-MWe field scale. Development of the SNRB{trademark} process at B&W began with pilot testing of high-temperature dry sorbent injection for SO{sub 2} removal in the 1960`s. Integration of NO{sub x} reduction was evaluated in the 1970`s. Pilot work in the 1980`s focused on evaluation of various NO{sub x} reduction catalysts, SO{sub 2} sorbents and integration of the catalyst with the baghouse. This early development work led to the issuance of two US process patents to B&W - No. 4,309,386 and No. 4,793,981. An additional patent application for improvements to the process is pending. The OCDO was instrumental in working with B&W to develop the process to the point where a larger scale demonstration of the technology was feasible. This report represents the completion of Milestone M14 as specified in the Work Plan. B&W tested the SNRB{trademark} pollution control system at a 5-MWe demonstration facility at Ohio Edison`s R. E. Burger Plant located near Shadyside, Ohio. The design and operation were influenced by the results from laboratory pilot testing at B&W`s Alliance Research Center. The intent was to demonstrate the commercial feasibility of the SNRB{trademark} process. The SNRB{trademark} facility treated a 30,000 ACFM flue gas slipstream from Boiler No. 8. Operation of the facility began in May 1992 and was completed in May 1993.

  14. Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

    Science.gov (United States)

    Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

    2014-01-01

    The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

  15. BAFF is involved in macrophage-induced bortezomib resistance in myeloma.

    Science.gov (United States)

    Chen, Jing; He, Donghua; Chen, Qingxiao; Guo, Xing; Yang, Li; Lin, Xuanru; Li, Yi; Wu, Wenjun; Yang, Yang; He, Jingsong; Zhang, Enfan; Yi, Qing; Cai, Zhen

    2017-11-02

    We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA. We also showed that the MM-macrophage interaction through BAFF and its receptors was primarily mediated by the activation of Src, Erk1/2, Akt, and nuclear factor kappa B signaling and the suppression of caspase activation induced by bort. Our data demonstrated that BAFF played a functional role in the macrophage-mediated resistance of MM cells to bort, suggesting that targeting BAFF may provide a basis for the molecular- and immune-targeted therapeutic approach.

  16. Effect of fiber coatings on room and elevated temperature mechanical properties of Nicalon trademark fiber reinforced Blackglas trademark ceramic matrix composites (CMCs)

    International Nuclear Information System (INIS)

    Aly, E.I.; Freitag, D.W.; Littlefield, J.E.

    1993-01-01

    With the development of silicon organometallic preceramic polymers as precursors for producing oxidation resistant ceramic matrices, through the polymer pyrolysis route, the fabrication of lightweight, complex advanced aircraft and missile structures from fiber reinforced composites is increasingly becoming more feasible. Besides refinement of processing techniques, the potential for achieving this objective depends upon identifying and developing the proper debond barrier coating layer, between the fiber and the matrix, for optimization of strength, toughness, and durability properties. Blackglas trademark based CMC's reinforced with Nicalon trademark SiC fibers with different types of coatings were fabricated. Coating schemes evaluated include CVD applied single layer boron nitride (BN) composition, dual-layer coatings of BN/SiC, and triple-layer coatings of SiC BN/SiC. Results of tensile and flexural property tests, scanning electron microscopy (SEM) of fracture surfaces, and auger electron spectroscopy (AES) microanalysis of the fiber/matrix interface have been discussed

  17. Task QA plan for Modified Prototypic Hydragard trademark Sampler Overflow System Demonstration at TNX

    International Nuclear Information System (INIS)

    Snyder, T.K.

    1993-01-01

    The primary objective of this task is to evaluate the proposed design modifications to the sample system, including the adequacy of the recommended eductor and the quality of samples obtained from the modified system. Presently, the sample streams are circulated from the originating tank, through a Hydragard trademark sampler system, and back to the originating tank. The overflow from the Hydragard trademark sampler flows to the Recycle Collection Tank (RCT). This report outlines the planned quality assurance controls for the design modification task, including organization and personnel, surveillances, and records package

  18. Hunting Goodwill: A History of the Concept of Goodwill in Trademark Law

    OpenAIRE

    Bone, Robert G.

    2006-01-01

    A deep tension lies at the heart of trademark law. On the one hand, the law’s core mission is to facilitate the transmission of accurate information to the market. Hence the touchstone of liability has always been the likelihood of consumer confusion. On the other hand, it is also customary to refer to trademark law as protecting goodwill in a mark. The problems arise because these two ways of formulating the goal push in different normative directions and create a policy tension that frus...

  19. 76 FR 59114 - Request for Comments on Establishment of a One-Year Retention Period for Trademark-Related Papers...

    Science.gov (United States)

    2011-09-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE... Registration System AGENCY: United States Patent and Trademark Office, Commerce. ACTION: Notice. SUMMARY: The... disposal, the relevant trademark applicant or owner files a request to correct the electronic record in...

  20. 75 FR 39493 - United States Patent and Trademark Office Draft Strategic Plan for FY 2010-2015

    Science.gov (United States)

    2010-07-09

    ... administration and leadership of the agency is a revision of the FY 2007-2012 strategic plan. The USPTO's current... United States Patent and Trademark Office United States Patent and Trademark Office Draft Strategic Plan...) draft strategic plan for fiscal years (FY) 2010-2015 is available for public review and comment. The...

  1. Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

    Science.gov (United States)

    Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

    2014-01-01

    The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

  2. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  3. System 80+{trademark} Standard Design: CESSAR design certification. Volume 16: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report, entitled Combustion Engineering Standard Safety Analysis Report - Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80+{trademark} Standard Design. This Volume 16 details the application of Human Factors Engineering in the design process.

  4. The parody defense against trademark bullies: analysis of the Louis Vuitton vs. Mob Case

    Directory of Open Access Journals (Sweden)

    Daniela Molano Lozano

    2017-12-01

    Full Text Available The present note aims to give a better understanding of parody as an exception to the exclusive rights provided to copyright holders and trademark owners. With this purpose, the note uses the Louis Vuitton vs. MOB case as a reference.

  5. System 80+{trademark} Standard Design: CESSAR design certification. Volume 8: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80{sup +}{trademark} Standard Design. This volume 8 provides a description of instrumentation and controls.

  6. System 80+{trademark} Standard Design: CESSAR design certification. Volume 11: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80{sup +}{trademark} Standard Design. This volume 11 discusses Radiation Protection, Conduct of Operations, and the Initial Test Program.

  7. System 80+{trademark} Standard Design: CESSAR design certification. Volume 9: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report, entitled Combustion Engineering Standard Safety Analysis Report -- Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These volumes describe the Combustion Engineering, Inc. System 80{sup +}{trademark} Standard Design. This volume 9 discusses Electric Power and Auxiliary Systems.

  8. 19 CFR 148.55 - Exemption for articles bearing American trademark.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Exemption for articles bearing American trademark. 148.55 Section 148.55 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... judicial order or in the liquidation of an estate is not subject to the provisions of this paragraph. (c...

  9. 25 CFR 308.2 - Certificates of genuineness to be attached to trade-marks.

    Science.gov (United States)

    2010-04-01

    ... ENTERPRISES CONCERNED WITH THE PRODUCTION AND SALE OF GENUINE HANDICRAFTS § 308.2 Certificates of genuineness to be attached to trade-marks. (a) To insure the widest distribution of genuine Indian handicraft... Indian craftsmen, for the purpose of the production and sale of such handicraft products, the Indian Arts...

  10. Expanding the Intellectual Property Knowledge Base at University Libraries: Collaborating with Patent and Trademark Resource Centers

    Science.gov (United States)

    Wallace, Martin; Reinman, Suzanne

    2018-01-01

    Patent and Trademark Resource Centers are located in libraries throughout the U.S., with 43 being in academic libraries. With the importance of incorporating a knowledge of intellectual property (IP) and patent research in university curricula nationwide, this study developed and evaluated a partnership program to increase the understanding of IP…

  11. Improvement of Legislation on Administrative Responsibility for the Illegal Use of Trademarks and Application Practice

    Directory of Open Access Journals (Sweden)

    Permyakova N. A.

    2012-11-01

    Full Text Available The article deals with the issues of legislation improvement concerning administrative responsibility for illegal use of trademarks. The author exposes problematic questions of law enforcement on bringing to administrative responsibility under Art. 14.10 of the RF Administrative Code

  12. “Territorial Aspects of Community Trademarks – the Single Market’s Splendid Sovereignty”

    NARCIS (Netherlands)

    Machnicka, A.A.

    2014-01-01

    Intellectual property rights are traditionally subject to the principle of territoriality, meaning that their protection is extended only to the territorial jurisdiction of the national granting authority (usually patent and trademark offices). In the light of cross-border commercial expansion that

  13. Determination of Bortezomib in API Samples Using HPLC: Assessment of Enantiomeric and Diastereomeric Impurities.

    Science.gov (United States)

    Kamalzadeh, Zahra; Babanezhad, Esmaeil; Ghaffari, Solmaz; Mohseni Ezhiyeh, Alireza; Mohammadnejad, Mahdieh; Naghibfar, Mehdi; Bararjanian, Morteza; Attar, Hossein

    2017-08-01

    A new, normal phase high performance liquid chromatography (NP-HPLC) method was developed for separation of Bortezomib (BZB) enantiomers and quantitative determination of (1S,2R)-enantiomer of BZB in active pharmaceutical ingredient (API) samples. The developed method was validated based on International Conference on Harmonisation (ICH) guidelines and it was proved to be accurate, precise and robust. The obtained resolution (RS) between the enantiomers was more than 2. The calibration curve for (1S,2R)-enantiomer was found to be linear in the concentration range of 0.24-5.36 mg/L with regression coefficient (R2) of 0.9998. Additionally, the limit of detection (LOD) and limit of quantification (LOQ) were 0.052 and 0.16 mg/L, respectively. Also, in this study, a precise, sensitive and robust gradient reversed-phase HPLC (RP-HPLC) method was developed and validated for determination of BZB in API samples. The detector response was linear over the concentration range of 0.26-1110.5 mg/L. The values of R2, LOD and LOQ were 0.9999, 0.084 and 0.25 mg/L, respectively. For both NP-HPLC and RP-HPLC methods, all of the RSD (%) values obtained in the precision study were 2,000 and RS > 2.0. The performance of two common integration methods of valley to valley and drop perpendicular for drawing the baseline between two adjacent peaks were investigated for the determination of diastereomeric impurity (Imp-D) in the BZB-API samples. The results showed that the valley to valley method outperform the drop perpendicular method for calculation of Imp-D peak areas. Therefore, valley to valley method was chosen for peak integration. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in Echinococcus granulosus larval stage.

    Directory of Open Access Journals (Sweden)

    María Celeste Nicolao

    Full Text Available Cystic echinococcosis (CE is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz, a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0.05. After 48 h of exposure to this drug, it was triggered a mRNA overexpression of chaperones (Eg-grp78 and Eg-calnexin and of Eg-ire2/Eg-xbp1 (the conserved UPR pathway branch in protoscoleces. No changes were detected in the transcriptional expression of chaperones in Bz-treated metacestodes, thus allowing ER stress to be evident and viability to highly decrease in comparison with protoscoleces. We also found that Bz treatment activated the autophagic process in both larval forms. These facts were evidenced by the increase in the amount of transcripts of the autophagy related genes (Eg-atg6, Eg-atg8, Eg-atg12, Eg-atg16 together with the increase in Eg-Atg8-II detected by western blot and by in toto immunofluorescence labeling. It was further confirmed by direct observation of autophagic structures by electronic microscopy. Finally, in order to determine the impact of autophagy induction on Echinococcus cell viability, we evaluated the efficacy of Bz in combination with rapamycin and a synergistic cytotoxic effect on protoscolex viability was observed when both drugs were used together. In conclusion, our findings demonstrated that Bz induced endoplasmic reticulum stress, autophagy and subsequent death allowing to identify unstudied parasite-host pathways that could provide a new insight for control of parasitic diseases.

  15. Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL amyloidosis.

    Directory of Open Access Journals (Sweden)

    Surbhi Sidana

    Full Text Available Randomized studies have shown that bortezomib (BTZ can be given weekly via intravenous (IV route or twice weekly via subcutaneous (SC route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001 while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15. Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008 while the likelihood of not achieving a response (= partial response or better was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56 for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001.Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

  16. An NMR Study of the Bortezomib Degradation under Clinical Use Conditions

    Directory of Open Access Journals (Sweden)

    Adele Bolognese

    2009-01-01

    Full Text Available The (R-3-methyl-1-((S-3-phenyl-2-(pyrazine-2-carboxamidopropanamidobutyl-boronic acid, bortezomib (BTZ, which binds the 20S proteasome subunit and causes a large inhibition of its activity, is a peptidomimetic boronic drug mainly used for the treatment of multiple myeloma. Commercial BTZ, stabilized as mannitol derivative, has been investigated under the common conditions of the clinical use because it is suspected to be easily degradable in the region of its boronic moiety. Commercial BTZ samples, reconstituted according to the reported commercial instructions and stored at 4∘C, were analyzed by high-field nuclear magnetic resonance spectroscopy in comparison with identical samples bubbled with air and argon, respectively. All the samples remained unchanged for a week. After a month, the air filled samples showed the presence of two main degradation products (6% of starting material, the N-(1-(1-hydroxy-3-methylbutylamino-1-oxo-3-phenylpropan-2-yl pyrazine-2-carboxamide (BTZ1; 5%, determined from NMR integration and the (S-N-(1-(3-methylbutanamido-1-oxo-3-phenylpropan-2-ylpyrazine-2-carboxamide (BTZ2; 1%, determined from NMR integration, identified on the basis of their chemical and spectroscopic properties. The BTZ1 and BTZ2 finding suggests that, under the common condition of use and at 4∘C, commercial BTZ-mannitol is stable for a week, and that, in time, it undergoes slow oxidative deboronation which partially inactivates the product. Low temperature and scarce contact with air decrease the degradation process.

  17. Characterization of radioactive contamination inside pipes with the Pipe Explorer{trademark} system. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cremer, C.D.; Kendrick, D.T.; Lowry, W.; Cramer, E.

    1997-09-30

    The Department of Energy (DOE) is currently in the process of decommissioning and dismantling many of its nuclear materials processing facilities that have been in use for several decades. Site managers throughout the DOE complex must employ the safest and most cost effective means to characterize, remediate and recycle or dispose of hundreds of miles of potentially contaminated piping and duct work. The DOE discovered that standard characterization methods were inadequate for its pipes, drains, and ducts because many of the systems are buried or encased. In response to the DOE`s need for a more specialized characterization technique, Science and Engineering Associates, Inc. (SEA) developed the Pipe Explorer{trademark} system through a DOE Office of Science and Technology (OST) contract administered through the Federal Energy Technology Center (FETC). The purpose of this report is to serve as a comprehensive overview of all phases of the Pipe Explorer{trademark} development project. The report is divided into 6 sections. Section 2 of the report provides an overview of the Pipe Explorer{trademark} system, including the operating principles of using an inverting membrane to tow sensors into pipes. The basic components of the characterization system are also described. Descriptions of the various deployment systems are given in Section 3 along with descriptions of the capabilities of the deployment systems. During the course of the development project 7 types of survey instruments were demonstrated with the Pipe Explorer{trademark} and are a part of the basic toolbox of instruments available for use with the system. These survey tools are described in Section 4 along with their typical performance specifications. The 4 demonstrations of the system are described chronologically in Section 5. The report concludes with a summary of the history, status, and future of the Pipe Explorer{trademark} system in Section 6.

  18. Characterization of radioactive contamination inside pipes with the Pipe Explorer trademark system. Final report

    International Nuclear Information System (INIS)

    Cremer, C.D.; Kendrick, D.T.; Lowry, W.; Cramer, E.

    1997-01-01

    The Department of Energy (DOE) is currently in the process of decommissioning and dismantling many of its nuclear materials processing facilities that have been in use for several decades. Site managers throughout the DOE complex must employ the safest and most cost effective means to characterize, remediate and recycle or dispose of hundreds of miles of potentially contaminated piping and duct work. The DOE discovered that standard characterization methods were inadequate for its pipes, drains, and ducts because many of the systems are buried or encased. In response to the DOE's need for a more specialized characterization technique, Science and Engineering Associates, Inc. (SEA) developed the Pipe Explorer trademark system through a DOE Office of Science and Technology (OST) contract administered through the Federal Energy Technology Center (FETC). The purpose of this report is to serve as a comprehensive overview of all phases of the Pipe Explorer trademark development project. The report is divided into 6 sections. Section 2 of the report provides an overview of the Pipe Explorer trademark system, including the operating principles of using an inverting membrane to tow sensors into pipes. The basic components of the characterization system are also described. Descriptions of the various deployment systems are given in Section 3 along with descriptions of the capabilities of the deployment systems. During the course of the development project 7 types of survey instruments were demonstrated with the Pipe Explorer trademark and are a part of the basic toolbox of instruments available for use with the system. These survey tools are described in Section 4 along with their typical performance specifications. The 4 demonstrations of the system are described chronologically in Section 5. The report concludes with a summary of the history, status, and future of the Pipe Explorer trademark system in Section 6

  19. Trademark dilution: comparing the effects of blurring and tarnishment cases over brand equity

    Directory of Open Access Journals (Sweden)

    Macías Washington

    2017-09-01

    Full Text Available Trademark dilution is, in a general sense, a reduction in brand equity due to the unauthorized use of the trademark by third parties (junior brands. Although there are two types of dilution, blurring and tarnishment, existing academic empirical evidence only relates to blurring cases, showing its damage to some variables related to brand associations in consumers’ minds. Literature also shows the moderating role of the similarity between junior brands, but this evidence is not complete unless presumable tarnishment cases are analyzed. This paper compares the effect of two types of junior brands over strength of associations and brand equity of famous trademarks. An experimental approach was applied with a sample of 372 undergraduate students, users of two famous convenience brands. Junior brands use identical or similar famous brand names in different product categories, offering a continuous of similarity levels, so the moderating effect of this variable is analyzed. Results show that: (i dependent variables are reinforced when junior brands are perceived as very similar, and diluted above some degree of dissimilarity; (ii dilution increases the more dissimilar the junior brand. However, although they have a high degree of dissimilarity, cases of presumable tarnishment, might not always produce dilution. Besides, they suggest that the effect induced by similarity is not linear. These findings are discussed through the lenses of marketing and psychology theories. The study represents a contribution to the field, providing evidence not only from blurring cases, but also from supposed tarnishing imitators, comparing their effects and showing the limited moderating effect of similarity. The boundary conditions of similarity effects in trademark dilution literature have not been discussed previously. Finally, main implications for managers are highlighted, given the negative effects that trademark dilution may entail at firm level.

  20. Bortezomib for antibody mediated rejection treatment: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City.

    Science.gov (United States)

    Leyva, Sergio; Marino-Vázquez, Lluvia A; Reyes-Loaeza, Jorge A; Vega, Olynka; Uribe-Uribe, Norma; Alberú, Josefina; Morales-Buenrostro, Luis E

    2009-01-01

    The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response neither to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal.

  1. Expression of TRIM28 correlates with proliferation and Bortezomib-induced apoptosis in B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Zhang, Pei-Pei; Ding, Da-Zhi; Shi, Bing; Zhang, Shu-Qing; Gu, Ling-Li; Wang, Yu-Chan; Cheng, Chun

    2018-03-23

    Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has been reported playing a role in regulating DNA damage response (DDR), cell differentiation, immune response, and tumorigenesis. The present study was performed to explore the biological function and clinical significance of TRIM28 in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high expression of TRIM28 was positively associated with the poorer survival of B-NHL patients as an independent prognostic factor. In addition, TRIM28 could promote the B-NHL cells proliferation through modulating cell cycle progression. The change of cyclinA, P21, and PCNA expression after TRIM28 expression modified further illustrated the mechanism in which TRIM28 participated in cell proliferation progression. Moreover, inhibition TRIM28 expression in B-NHL cells enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis pathway. Taken together, the present study showed that TRIM28 functions as a tumor promoter in B-NHL and may be a novel target for drug resistance to Bortezomib.

  2. Phase 1 study of radiosensitization using bortezomib in patients with relapsed non-Hodgkin lymphoma receiving radioimmunotherapy with 131I-tositumomab.

    Science.gov (United States)

    Elstrom, Rebecca L; Ruan, Jia; Christos, Paul J; Martin, Peter; Lebovic, Daniel; Osborne, Joseph; Goldsmith, Stanley; Greenberg, June; Furman, Richard R; Avram, Anca; Putman, Ryan; Chapman, Erica; Mazumdar, Madhu; Griffith, Kent; Coleman, Morton; Leonard, John P; Kaminski, Mark S

    2015-02-01

    Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin lymphomas (NHLs), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This phase 1 dose-escalation study evaluated escalating doses of bortezomib combined with 131I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. The maximum tolerated dose (MTD) was determined to be 0.9 mg/m2 bortezomib, in combination with a standard dose of 75 cGy 131I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CRs), with 82% CR in patients with follicular lymphoma (FL). At a median follow-up of 7 months, median progression-free survival was 7 months, and seven of 11 patients with FL remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with 131I-tositumomab with promising response rates.

  3. Bortezomib before and after high-dose therapy in myeloma : Long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; Kooy, M. van Marwijk; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  4. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; van Marwijk Kooy, M.; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    2018-01-01

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  5. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients

    NARCIS (Netherlands)

    Waal, de Esther G. M.; de Munck, Linda; Hoogendoorn, Mels; Woolthuis, Gerhard; van der Velden, Annette; Tromp, Yvonne; Vellenga, Edo; Hovenga, Sjoerd

    2015-01-01

    Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of

  6. Bortezomib sensitivity of acute myeloid leukemia CD34(+) cells can be enhanced by targeting the persisting activity of NF-kappa B and the accumulation of MCL-1

    NARCIS (Netherlands)

    Bosman, Matthieu Cornelis Johannes; Schuringa, Jan Jacob; Quax, Wilhelmus Johannes; Vellenga, Edo

    Sustained NF-kappa B activation is often observed in acute myeloid leukemia (AML); therefore, proteasome inhibition has been proposed to efficiently target AML cells. In this study, we questioned whether leukemic stem cell-enriched CD34(+) cells are sensitive to the proteasome inhibitor bortezomib.

  7. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Fabrizio Accardi

    2015-01-01

    Full Text Available Multiple myeloma (MM is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.

  8. A genome-wide association study identifies a novel locus for bortezomib-induced peripheral neuropathy in European patients with multiple myeloma

    NARCIS (Netherlands)

    F. Magrangeas (Florence); R. Kuiper (Ruud); H. Avet-Loiseau (Hervé); Gouraud, W. (Wilfried); Guerin-Charbonnel, C. (Catherine); Ferrer, L. (Ludovic); Aussem, A. (Alexandre); Elghazel, H. (Haytham); Suhard, J. (Jérôme); Sakissian, H.D. (Henri Der); M. Attal (Michel); Munshi, N.C. (Nikhil C.); P. Sonneveld (Pieter); Dumontet, C. (Charles); P. Moreau; M. van Duin (Mark); Campion, L. (Löôc); S. Minvielle (S)

    2016-01-01

    textabstractPurpose: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity. Experimental Design: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk

  9. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    . The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. Results: In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment....... We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion......: There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome....

  10. DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma.

    Science.gov (United States)

    Kropff, Martin; Liebisch, Peter; Knop, Stefan; Weisel, Katja; Wand, Hannes; Gann, Claudia-Nanette; Berdel, Wolfgang E; Einsele, Herrmann

    2009-11-01

    A clinical trial was initiated to evaluate the recommended dose of cyclophosphamide in combination with bortezomib and dexamethasone as induction treatment before stem cell transplantation for younger patients with newly diagnosed multiple myeloma (MM). Thirty patients were treated with three 21-day cycles of bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 plus dexamethasone 40 mg on the day of bortezomib injection and the day after plus cyclophosphamide at 900, 1,200, or 1,500 mg/m(2) on day 1. The maximum tolerated dose of cyclophosphamide was defined as 900 mg/m(2). At this dose level, 92% of patients achieved at least a partial response. The overall response rate [complete response (CR) plus partial response (PR)] across all dose levels was 77%, with a 10% CR rate. No patient experienced progressive disease. The most frequent adverse events were hematological and gastrointestinal toxicities as well as neuropathy. The results suggest that bortezomib in combination with cyclophosphamide at 900 mg/m(2) and dexamethasone is an effective induction treatment for patients with newly diagnosed MM that warrants further investigation.

  11. Subcutaneous bortezomib in multiple myeloma patients induces similar therapeutic response rates as intravenous application but it does not reduce the incidence of peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

  12. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

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    Vogel Ulla

    2010-08-01

    Full Text Available Abstract Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion, *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

  13. Galectin-3C inhibits tumor growth and increases the anticancer activity of bortezomib in a murine model of human multiple myeloma.

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    Leonardo Mirandola

    Full Text Available Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM. Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM.

  14. Anti-leukemic activity of bortezomib and carfilzomib on B-cell precursor ALL cell lines.

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    Kazuya Takahashi

    Full Text Available Prognosis of childhood acute lymphoblastic leukemia (ALL has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ, a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+ ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response. Even in Ph-negative ALL cell lines, IKZF1 deletion and bilallelic loss of CDKN2A were independently associated with higher BTZ sensitivity. BTZ showed only marginal cross-resistance to four representative chemotherapeutic agents (vincristine, dexamethasone, l-asparaginase, and daunorubicin in B-cell precursor-ALL cell lines. To improve the efficacy and safety of proteasome inhibitor combination chemotherapy, we also analyzed the anti-leukemic activity of carfilzomib (CFZ, a second-generation proteasome inhibitor, as a substitute for BTZ. CFZ showed significantly higher activity than BTZ in the majority of ALL cell lines except for the P-glycoprotein-positive t(17;19 ALL cell lines, and IKZF1 deletion was also associated with a favorable response to CFZ treatment. P-glycoprotein inhibitors effectively restored the sensitivity to CFZ, but not BTZ, in P-glycoprotein-positive t(17;19 ALL cell lines. P-glycoprotein overexpressing ALL cell line showed a CFZ-specific resistance, while knockout of P-glycoprotein by genome editing with a CRISPR/Cas9 system sensitized P-glycoprotein-positive t(17;19 ALL cell line to CFZ. These observations suggested that IKZF1 deletion could be a useful biomarker to predict good

  15. Hypoxia selects bortezomib-resistant stem cells of chronic myeloid leukemia.

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    Michele Tanturli

    Full Text Available We previously demonstrated that severe hypoxia inhibits growth of Chronic Myeloid Leukemia (CML cells and selects stem cells where BCR/Abl(protein is suppressed, although mRNA is not, so that hypoxia-selected stem cells, while remaining leukemic, are independent of BCR/Abl signaling and thereby refractory to Imatinib-mesylate. The main target of this study was to address the effects of the proteasome inhibitor Bortezomib (BZ on the maintenance of stem or progenitor cells in hypoxic primary cultures (LC1, by determining the capacity of LC1 cells to repopulate normoxic secondary cultures (LC2 and the kinetics of this repopulation. Unselected K562 cells from day-2 hypoxic LC1 repopulated LC2 with rapid, progenitor-type kinetics; this repopulation was suppressed by BZ addition to LC1 at time 0, but completely resistant to day-1 BZ, indicating that progenitors require some time to adapt to stand hypoxia. K562 cells selected in hypoxic day-7 LC1 repopulated LC2 with stem-type kinetics, which was largely resistant to BZ added at either time 0 or day 1, indicating that hypoxia-selectable stem cells are BZ-resistant per se, i.e. before their selection. Furthermore, these cells were completely resistant to day-6 BZ, i.e. after selection. On the other hand, hypoxia-selected stem cells from CD34-positive cells of blast-crisis CML patients appeared completely resistant to either time-0 or day-1 BZ. To exploit in vitro the capacity of CML cells to adapt to hypoxia enabled to detect a subset of BZ-resistant leukemia stem cells, a finding of particular relevance in light of the fact that our experimental system mimics the physiologically hypoxic environment of bone marrow niches where leukemia stem cells most likely home and sustain minimal residual disease in vivo. This suggests the use of BZ as an enhanced strategy to control CML. in particular to prevent relapse of disease, to be considered with caution and to need further deepening.

  16. Tritium stripping in a nitrogen glove box using palladium/zeolite and SAES St 198 trademark

    International Nuclear Information System (INIS)

    Klien, J.E.; Wermer, J.R.

    1995-01-01

    Glove box clean-up experiments were conducted in a nitrogen glove box using palladium deposited on zeolite (Pd/z) and a SAES St 198 trademark getter as tritium stripping materials. Protium/deuterium samples spiked with tritium were released into a 620 liter glove box to simulate tritium releases in a 10,500 liter glove box. The Pd/z and the SAES St 198 trademark stripper beds produced a reduction in tritium activity of approximately two to three orders of magnitude and glove box clean-up was limited by a persistent background tritium activity level. Attempts to significantly reduce the glove box activity to lower levels without purging were unsuccessful

  17. FRHAM-TEX trademark cool suit - OST reference No. 1854. Deactivation and decommissioning focus area

    International Nuclear Information System (INIS)

    1998-02-01

    This paper describes a demonstration project for the FRHAM-TEX Cool Suit trademark manufactured by FRHAM Safety Products. It is a one-piece, disposable, breathable, waterproof coverall designed to permit moisture generated by the wearer to be transmitted outside the suit. The performance of this suit was compared to a Tyvek reg-sign suit as a baseline. The suit is proposed as safety ware for workers at decontamination and decommissioning projects

  18. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicin and Aspirin {sup trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Weichgrebe, D.; Danilova, E.; Rosenwinkel, K.H. [Inst. of Water Quality and Waste Management, Univ. of Hannover, Hannover (Germany); Vedenjapin, A.; Baturova, M. [Inst. of Organic Chemistry, Russian Academy of Science, Moscow (Russian Federation)

    2003-07-01

    The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

  19. Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502

    Science.gov (United States)

    Attar, Eyal C.; Johnson, Jeffrey L.; Amrein, Philip C.; Lozanski, Gerard; Wadleigh, Martha; DeAngelo, Daniel J.; Kolitz, Jonathan E.; Powell, Bayard L.; Voorhees, Peter; Wang, Eunice S.; Blum, William; Stone, Richard M.; Marcucci, Guido; Bloomfield, Clara D.; Moser, Barry; Larson, Richard A.

    2013-01-01

    Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. PMID:23129738

  20. Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage.

    Science.gov (United States)

    Premkumar, Daniel R; Jane, Esther P; Agostino, Naomi R; DiDomenico, Joseph D; Pollack, Ian F

    2013-02-01

    Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. Copyright © 2011 Wiley Periodicals, Inc.

  1. RESEARCH ON THE EVOLUTION OF THE TOP ROMANIAN TRADEMARKS IN THE DOMESTIC MARKET

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    Agatha POPESCU

    2015-04-01

    Full Text Available The paper analyzed the position of the Romanian trademarks using the data provided by Unlock Market Research Company in 2010 and 2014. The statistical parameters: average, variance, standard deviation and variation coefficient, and the Point Method and Comparison Method were used to process the collected data. In 2014, among the top 50 brands in Romania's market, the top 10 positions were occupied by the following trademarks: Borsec, Dero, Gerovital, Dorna, Arctic, Dacia, Elmiplant, Aqua Carpatica, Farmec and Petrom. Food industry came on the 1st position with 17 brands and on the 3rd position after telephony and finance and banking, based on the average positions of its trademarks. By field of activity, based on the average position, the 1st three positions were occupied by Machinery construction and Chemical and extractive industry, Alcoholic beverages, and Wood working industry. On the last position was situated Telephony. As a final conclusion, consumers behavior reflected an intensive orientation to the Romanian brands belonging to food industry, care and health sector and also of the appliances for household reflecting a new behavior to assure a higher living standards.

  2. Resolution of bilateral cystoid macular edema and subfoveal serous retinal detachments after treatment with bortezomib in a patient with "smoldering" multiple myeloma.

    Science.gov (United States)

    Grannis, Charity H; Dewan, Vinay N; Wang, Robert C

    2014-01-01

    To describe a case of a patient with multiple myeloma without extraocular end-organ damage but with cystoid macular edema and macular detachments who was treated with bortezomib and dexamethasone. There was a complete resolution of retinal and subretinal fluid and significant improvement of vision. The patient's ocular disease was monitored with visual acuity, dilated fundus examinations, and optical coherence tomography before, during, and after treatment. The patient in this case report was a 43-year-old African American man with a medical history of untreated, "smoldering" multiple myeloma, hypertension, hyperlipidemia who presented to our clinic with progressive painless loss of vision in both eyes over 6 weeks. Before treatment with bortezomib and dexamethasone, the patient had complaints of confusion, muscle stiffness, joint pain, and 20-lb unintentional weight loss; however, he did not have hypercalcemia, renal insufficiency, anemia, or bone lesions typical of active multiple myeloma. The bilateral cystoid macular edema and subfoveal neurosensory retinal detachments, noted on presentation and confirmed by optical coherence tomography, completely resolved over the course of treatment with bortezomib and dexamethasone. This case of bilateral cystoid macular edema and subfoveal neurosensory retinal detachments is remarkable for both its presentation and response to therapy. The macular edema and macular detachments along with nonspecific complaints of confusion, muscle stiffness, joint pain, and weight loss were the presenting signs and symptoms; signs typically used as guides to initiate treatment for multiple myeloma were not present. Macular edema in the context of paraproteinemia is usually associated with Waldenstrom's macroglobulinemia and has classically been reported as "silent" with respect to fluorescein angiography. Our patient has multiple myeloma and demonstrated leakage on fluorescein angiography. The case is also notable in that there was

  3. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study.

    Science.gov (United States)

    Dimopoulos, Meletios; Siegel, David S; Lonial, Sagar; Qi, Junyuan; Hajek, Roman; Facon, Thierry; Rosinol, Laura; Williams, Catherine; Blacklock, Hilary; Goldschmidt, Hartmut; Hungria, Vania; Spencer, Andrew; Palumbo, Antonio; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Sun, Linda; Vuocolo, Scott; Anderson, Kenneth C

    2013-10-01

    We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most

  4. Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice.

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    Elon C Roti Roti

    Full Text Available Increasing numbers of female patients survive cancer, but succumb to primary ovarian insufficiency after chemotherapy. We tested the hypothesis that Bortezomib (Bort protects ovaries from doxorubicin (DXR chemotherapy by treating female mice with Bort 1 hour prior to DXR. By preventing DXR accumulation in the ovary, Bort attenuated DXR-induced DNA damage in all ovarian cell types, subsequent γH2AFX phosphorylation, and resulting apoptosis in preantral follicles. Bort pretreatment extended the number of litters per mouse, improved litter size and increased pup weight following DXR treatment, thus increasing the duration of post-chemotherapy fertility and improving pup health. As a promising prophylactic ovoprotective agent, Bort does not interfere with cancer treatment, and is currently used as a chemotherapy adjuvant. Bort-based chemoprotection may preserve ovarian function in a non-invasive manner that avoids surgical ovarian preservation, thus diminishing the health complications of premature menopause following cancer treatment.

  5. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah

    2013-01-01

    improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc...... and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where...

  6. Development of a Continuum Damage Mechanics Material Model of a Graphite-Kevlar(Registered Trademark) Hybrid Fabric for Simulating the Impact Response of Energy Absorbing Kevlar(Registered Trademark) Hybrid Fabric for Simulating the Impact Response of Energy Absorbing

    Science.gov (United States)

    Jackson, Karen E.; Fasanella, Edwin L.; Littell, Justin D.

    2017-01-01

    This paper describes the development of input properties for a continuum damage mechanics based material model, Mat 58, within LS-DYNA(Registered Trademark) to simulate the response of a graphite-Kevlar(Registered Trademark) hybrid plain weave fabric. A limited set of material characterization tests were performed on the hybrid graphite-Kevlar(Registered Trademark) fabric. Simple finite element models were executed in LS-DYNA(Registered Trademark) to simulate the material characterization tests and to verify the Mat 58 material model. Once verified, the Mat 58 model was used in finite element models of two composite energy absorbers: a conical-shaped design, designated the "conusoid," fabricated of four layers of hybrid graphite-Kevlar(Registered Trademark) fabric; and, a sinusoidal-shaped foam sandwich design, designated the "sinusoid," fabricated of the same hybrid fabric face sheets with a foam core. Dynamic crush tests were performed on components of the two energy absorbers, which were designed to limit average vertical accelerations to 25- to 40-g, to minimize peak crush loads, and to generate relatively long crush stroke values under dynamic loading conditions. Finite element models of the two energy absorbers utilized the Mat 58 model that had been verified through material characterization testing. Excellent predictions of the dynamic crushing response were obtained.

  7. Bortezomib sensitizes human osteosarcoma cells to adriamycin-induced apoptosis through ROS-dependent activation of p-eIF2α/ATF4/CHOP axis.

    Science.gov (United States)

    Xian, Miao; Cao, Handi; Cao, Ji; Shao, Xuejing; Zhu, Difeng; Zhang, Ning; Huang, Ping; Li, Weixu; Yang, Bo; Ying, Meidan; He, Qiaojun

    2017-09-01

    Osteosarcoma is the most common bone cancer, and chemotherapy is currently indispensable for its treatment. Adriamycin has been claimed to be the most effective agent for osteosarcoma, however, the outcome of adriamycin chemotherapy remains unsatisfactory. Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed that the activation of p-eIF2α/ATF4/CHOP axis is the underlying associated mechanisms. First, we observed that bortezomib enhances adriamycin-mediated inhibition of cell proliferation and enhances the apoptosis in osteosarcoma cell lines. Moreover, this drug combination produced more potent tumor-growth inhibitory effects in human osteosarcoma cell line KHOS/NP xenografts. Our study showed that reactive oxygen species (ROS) plays an important role in apoptosis induced by adriamycin plus bortezomib, whereas ROS scavenger NAC could almost completely block the apoptosis induced by the combination treatment. Meanwhile, p-eIF2α is remarkably elevated in the combination group. As a result, ATF4 exhibits strong activation which consequently induces the activation of CHOP and leads to the cell death. Finally, 13 primary osteosarcoma cells demonstrated potent response to the combination treatment. In a human osteosarcoma patient-derived xenograft (PDX) model, our finding suggests that when combined with bortezomib, a relatively low dose of adriamycin produced more potent tumor-growth inhibitory effects without increased toxicity. Thus, our findings not only provide a promising combination strategy to overcome osteosarcoma but also shed new light on the strategy of combining increased ROS and inhibited proteasome to open up new opportunities for the clinical development of chemotherapy regimens. © 2017 UICC.

  8. Down-regulation of 11β-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis.

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    Yi Tao

    Full Text Available 11β-Hydroxysteroid dehydrogenases type 2 (11β-HSD2, a key regulator for pre-receptor metabolism of glucocorticoids (GCs by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

  9. p21(WAF1/CIP1 upregulation through the stress granule-associated protein CUGBP1 confers resistance to bortezomib-mediated apoptosis.

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    Cristina Gareau

    Full Text Available p21(WAF1/CIP1 is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown.We identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( =  PS-341/Velcade. This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis.We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1.

  10. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy.

    Directory of Open Access Journals (Sweden)

    Adam Szulkin

    Full Text Available Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit.We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers.As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect.The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma.

  11. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  12. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.

    Science.gov (United States)

    Santo, Loredana; Hideshima, Teru; Kung, Andrew L; Tseng, Jen-Chieh; Tamang, David; Yang, Min; Jarpe, Matthew; van Duzer, John H; Mazitschek, Ralph; Ogier, Walter C; Cirstea, Diana; Rodig, Scott; Eda, Homare; Scullen, Tyler; Canavese, Miriam; Bradner, James; Anderson, Kenneth C; Jones, Simon S; Raje, Noopur

    2012-03-15

    Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.

  13. Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study

    Directory of Open Access Journals (Sweden)

    Ki-Seong Eom

    2014-01-01

    Full Text Available We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n=89. Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7% were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%, while 26 patients achieved less than PR (35.6%. The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P=0.037. In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.

  14. Physicochemical characterization of different trademarks of compound Yerba Maté and their herbs

    Directory of Open Access Journals (Sweden)

    Griselda Patricia Scipioni

    2007-07-01

    Full Text Available The objectives of this study were to evaluate the physicochemical characteristics of the main herbs used in the mixture of yerba maté with other aromatic herbs and the characterization of the trademarks of compound yerba maté. Moisture, water extract, total ash, acid-insoluble ash and caffeine concentration were determined. Results showed higher values of moisture content, total and aci-insoluble ash and lower water extracts in the herbs. Determinations were carried out in nine trademarks of compound yerba maté. In most cases they complied with the standards of the country with the exception of one trademark from Argentina.A erva-mate composta é um produto que se consome amplamente na região do MERCOSUL. Obtém-se misturando erva-mate com outras ervas aromáticas. O objetivo desta pesquisa foi o estudo das características físico-químicas das principais ervas usadas na mistura e a caracterização das marcas de erva-mate composta. Determinou-se a umidade, extração de água, cinzas totais, cinzas insolúveis ácidas e a concentração de cafeína. Encontraram-se nas ervas, valores padrões diferentes aos da erva-mate tais como valores maiores de conteúdo de umidade, cinzas totais, cinzas insolúveis ácidas e menores extratos de água. Fizeram-se determinações em nove marcas de erva-mate composta. Na maioria dos casos, cumpriam com as normas do país, exceto uma marca da Argentina

  15. Characterization of radioactive contamination inside pipes with the Pipe Explorer trademark system

    International Nuclear Information System (INIS)

    Kendrick, D.T.; Cremer, C.D.; Lowry, W.; Cramer, E.

    1995-01-01

    The U.S. Department of Energy's nuclear facility decommissioning program needs to characterize radiological contamination inside piping systems before the pipe can be recycled, remediated, or disposed. Science and Engineering associates, Inc. under contract with the DOE Morgantown Energy Technology Center has developed and demonstrated the Pipe Explorer trademark system, which uses an inverting membrane to transport various characterization sensors into pipes. The basic process involves inverting (turning inside out) a tubular impermeable membrane under air pressure. A characterization sensor is towed down the interior of the pipe by the membrane. Advantages of this approach include the capability of deploying through constrictions in the pipe, around 90 degrees bends, vertically up and down, and in slippery conditions. Because the detector is transported inside the membrane (which is inexpensive and disposable), it is protected from contamination, which eliminates cross-contamination. Characterization sensors that have been demonstrated with the system thus far include: gamma detectors, beta detectors, video cameras, and pipe locators. Alpha measurement capability is currently under development. A remotely operable Pipe Explorer trademark system has been developed and demonstrated for use in DOE facilities in the decommissioning stage. The system is capable of deployment in pipes as small as 2-inch-diameter and up to 250 feet long. This paper describes the technology and presents measurement results of a field demonstration conducted with the Pipe Explorer trademark system at a DOE site. These measurements identify surface activity levels of U-238 contamination as a function of location in drain lines. Cost savings to the DOE of approximately $1.5 million dollars were realized from this one demonstration

  16. Champagne, Cognac, Rioja, Jerez and Vales dos Vinhedos: Conflicts between trademarks and geographical indications of wines and spirits in Brazil

    Directory of Open Access Journals (Sweden)

    da Silva Barbosa Patrícia Maria

    2016-01-01

    Full Text Available The world wine trade generated around 30 billion Euros in 2015. The wine consumer appreciates attributes such as tradition, quality and distinctiveness, characteristics that are associated with the terroir. In this segment, trademarks and geographical indications (GI are relevant distinctive signs for the consumers' choice. Issues involving the protection of these signs have become increasingly stronger in the same proportion of the trade growth. Wine GIs hold a long tradition in the international scenario, particularly the European. In Brazil, the trademarks have a broader protection history, and the GIs were only acknowledged with the 1996 Industrial Property Law. Nevertheless, Brazil stands out as an emergent market for wines. The databank of the National Institute of Industrial Property (INPI-Brazil shows that 30% of all applications for GI protection are for wines and spirits. Such figures indicate the growing importance of the GI for the segment. The purpose of this paper is to analyze the applications for trademarks and GIs for wines and spirits, based on the INPI databank. For such, some foreign GIs have been chosen, for their historic and commercial importance, as well as one national GI, the first acknowledged in the segment. Among the results, several applications for trademarks from different applicants containing the searched terms have been found. From these results, it is believed that the coexistence and overlap of trademarks and GIs indicate the need for a review of the national legislation.

  17. RangerMaster trademark: Real-time pattern recognition software for in-field analysis of radiation sources

    International Nuclear Information System (INIS)

    Murray, W.S.; Ziemba, F.; Szluk, N.

    1998-01-01

    RangerMaster trademark is the embedded firmware for Quantrad Sensor's integrated nuclear instrument package, the Ranger trademark. The Ranger trademark, which is both a gamma-ray and neutron detection system, was originally developed at Los Alamos National Laboratory for in situ surveys at the Plutonium Facility to confirm the presence of nuclear materials. The new RangerMaster trademark software expands the library of isotopes and simplifies the operation of the instrument by providing an easy mode suitable for untrained operators. The expanded library of the Ranger trademark now includes medical isotopes 99 Tc, 201 Tl, 111 In, 67 Ga, 133 Xe, 103 Pa, and 131 I; industrial isotopes 241 Am, 57 Co, 133 Ba, 137 Cs, 40 K, 60 Co, 232 Th, 226 Ra, and 207 Bi; and nuclear materials 235 U, 238 U, 233 U, and 239 Pu. To accomplish isotopic identification, a simulated spectrum for each of the isotopes was generated using SYNTH. The SYNTH spectra formed the basis for the knowledge-based expert system and selection of the regions of interest that are used in the pattern recognition system. The knowledge-based pattern recognition system was tested against actual spectra under field conditions

  18. Patents and Trademarks as Information Sources and the Turkish Patent Institute

    Directory of Open Access Journals (Sweden)

    Erdoğan Karaahmet

    1995-12-01

    Full Text Available The protection of industrial property rights in a country is an important factor in encouraging the invention activities, application of new technologies to industry, increasing foreign investment and supporting national and international trade. The present industrial property system of Turkey, which is one of the first countries in the world that started the protection of industrial property rights, includes protection of patents and trademarks only. This paper discusses the importance of access to technological and commercial information, describes the basic concepts of industrial property rights, and introduces the Turkish Patent Institute, its structure and functions along with information and documentation services it offers.

  19. An assessment of Microtox trademark as a biomonitoring tool for whole effluent testing for Los Alamos National Laboratory

    International Nuclear Information System (INIS)

    Zachritz, W.H. II; Morrow, J.

    1994-01-01

    Los Alamos National Laboratory (LANL) has special discharge problems relating to potential radioactive content of the effluent discharge waters. Because of this all testing must be performed on-site and results must be rapidly determined. There is a need to examine the development of a real-time procedure for effluent biomonitoring to met these site limitations. The Microtox trademark unit for toxicity testing is a microbially-based test system that shows great promise to be used for WET testing. The overall goal of this study is to develop an acceptable protocol for operational biomonitoring using the Microtox trademark toxicity test for LANL. The specific objectives include: development of an appropriate toxicity testing protocol using the Microtox trademark toxicity test for whole effluent toxicity testing and evaluation of the protocol based on factors such as sensitivity, response time, cost of analysis, and simplicity of operation

  20. An assessment of Microtox{trademark} as a biomonitoring tool for whole effluent testing for Los Alamos National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Zachritz, W.H. II; Morrow, J. [New Mexico State Univ., Las Cruces, NM (United States)

    1994-06-13

    Los Alamos National Laboratory (LANL) has special discharge problems relating to potential radioactive content of the effluent discharge waters. Because of this all testing must be performed on-site and results must be rapidly determined. There is a need to examine the development of a real-time procedure for effluent biomonitoring to met these site limitations. The Microtox{trademark} unit for toxicity testing is a microbially-based test system that shows great promise to be used for WET testing. The overall goal of this study is to develop an acceptable protocol for operational biomonitoring using the Microtox {trademark} toxicity test for LANL. The specific objectives include: development of an appropriate toxicity testing protocol using the Microtox{trademark} toxicity test for whole effluent toxicity testing and evaluation of the protocol based on factors such as sensitivity, response time, cost of analysis, and simplicity of operation.

  1. Development of the SEAMIST trademark concept for site characterization and monitoring

    International Nuclear Information System (INIS)

    Lowry, W.; Keller, C.

    1992-11-01

    SEAMIST trademark (Science and Engineering Associates Membrane Instrumentation and Sampling Technique) is a borehole liner and instrument emplacement technique with applications in contaminant monitoring and site characterization. The system incorporates an impermeable tubular membrane which is deployed in a borehole by inversion under pneumatic pressure. Once in place the membrane remains under internal pressure to support the borehole wall and seal the hole against air circulation. Instruments and sampling devices mounted on the surface of the membrane are pressed against the borehole wall to maintain intimate contact with the geologic media. The membrane is left pressurized with air for short term applications (less than a month, for example) or filled with sand for longer term semi-permanent installations. This effort developed the SEAMIST trademark system explicitly for vadose zone gas and pore fluid sampling in monitoring circumstances of particular interest to the DOE. The emplacement hardware, membrane materials, sampling components, and ancillary equipment were fabricated and field tested. Absorbent collector materials were shown in laboratory tests to wick water samples at metric potentials as high as 15 bars. Soil vapor sampling tubing and fittings were tested with the deployment system to assess their integrity during the emplacement process and achievable sampling rates. A technique for measuring effective gas permeability at multiple elevations in the borehole was analyzed and tested in the field

  2. Evaluating the Effectiveness of NASA's Destination Tomorrow(Trademark) 2000-2001 Program

    Science.gov (United States)

    Pinelli, Thomas E.; Perry, Jeannine

    2002-01-01

    NASA's Destination Tomorrow(trademark) series consists of 30-minute educational television programs that focus on NASA research, past, present, and future and are designed for educators, parents, and adult (lifelong) learners. Programs in this award-winning series follow a magazine style format with segments ranging from 3-5 minutes to 6-8 minutes. An associated web site provides summaries of stories and links to related program material. The development of the programs is based on educational theory, principles, and research as they pertain to how adults learn and apply knowledge. The five programs in the 2000-2001 season were produced in English and dubbed in Spanish. Telephone interviews with managers of cable access television stations were conducted in January 2002. NASA's Destination Tomorrow(trademark) interviewees reported that (1) from a programming standpoint, the most appealing aspects of the series are its production quality and educational value, (2) programs in the series are 'better than average' when compared to other education programming, (3) the programs are very credible, (4) the programs are successful in educating people about what NASA does, and (5) the programs have been 'very well received' by their audiences.

  3. Cost-effectiveness analysis of the SEAMIST trademark membrane system technology

    International Nuclear Information System (INIS)

    Henriksen, A.D.; Booth, S.R.

    1995-01-01

    SEAMIST trademark is a new technology that consists of an airtight membrane liner that is pneumatically emplaced inside the borehole. The positive air pressure inside the liner maintains the integrity of the borehole structure. Sampling ports with attached tubing, absorbent collectors, or various in situ measuring devices can be fabricated into the liner and used for monitoring volatile organic compounds (VOCs), semivolatile organic compounds (SVOCs), pesticides, herbicides, polynuclear aromatic hydrocarbons, polychlorinated biphenyls, or radioactive substances. In addition, small instruments can be guided through the lined borehole and measurements taken inside at specified intervals. The purpose of this study is to analyze the cost and performance effectiveness of this new technology. To do so, the authors constructed five hypothetical scenarios in which utilization of the SEAMIST trademark system can address various needs of the Department of Energy's environmental remediation program. Two of the scenarios involve vertical boreholes (or vertical instrument configurations) and two involve horizontal boreholes (or horizontal instrument configurations). The four scenarios jointly address contamination by VOCS, SVOCS, various water-soluble toxic substances, and low-level radioactive waste. One of the scenarios involves towing an instrument through a borehole and taking measurements of moisture levels in the surrounding soil

  4. SoilSaw trademark demonstration. Final report, September 1992--January 1995

    International Nuclear Information System (INIS)

    Saugier, K.; Isaac, R.E.

    1996-02-01

    The US Department of Energy (DOE) has identified leaking underground storage tanks and buried mixed waste at numerous sites within the DOE complex. Preventing these wastes from entering the environment is a challenging task. One method of preventing waste migration is to isolate the contaminants using subsurface containment barriers. Isolation and containment can be accomplished by both in situ and ex situ methods. This report describes a novel in situ construction method of forming vertical containment barriers (slurry walls) using the SoilSaw trademark Barrier System. The SoilSaw trademark Barrier System is shown to be a feasible process for constructing subsurface vertical containment barriers to depths of fifty feet. The process is most efficient in sandy soil (including free flowing sand) with barrier construction rates of over 130 square feet per minute. Productivity diminishes to approximately 30 square feet per minute as soils become harder and more cohesive. The present hardware is designed to form a barrier of approximately 12 inch in width. Additional barrier widths can be constructed with this technology by application of wider jet heads. The requirement for a varied arrangement of barrier widths is an increase in hydraulic horse power and additional jet heads

  5. SmartShelf trademark: Report of activities for fiscal year 1996

    International Nuclear Information System (INIS)

    Bell, Z.W.; Lawson, R.L.; Long, C.D.

    1996-01-01

    The SmartShelf trademark system is designated to maintain an up-to-the-minute inventory of containers or other assets. Through the use of Dallas Semiconductor touch memory devices affixed to containers and entrusted to authorized operators, the system can determine which operator added or removed which container and when the transaction occurred. Through the use of a PC-based data base system, reports of the current status of all containers and nodes can be generated in minutes. This report covers activities on the SmartShelf trademark project for the period 1 October 1995 through 30 September 1996. During this year, project team members have advanced the state of the hardware and software from rough prototypes to a working system ready for field trials.The project team has developed an intimate working knowledge of the hardware and software, and has become expert at implementations of Dallas Semiconductor touch memory devices. System hardware includes a desktop PC running LabView and Microsoft Access, and an STD-bus 8086 computer to monitor container storage locations (nodes). The STD-bus computer monitors up to 128 nodes, and responds to operator actions (adding or removing containers) within 10 seconds. The PC uses LabView software to query the STD-bus machine to obtain records of transactions, and to download configuration information. Microsoft Access is used to store the transactions and configuration data in a user-accessible form

  6. SoilSaw{trademark} demonstration. Final report, September 1992--January 1995

    Energy Technology Data Exchange (ETDEWEB)

    Saugier, K.; Isaac, R.E.

    1996-02-01

    The US Department of Energy (DOE) has identified leaking underground storage tanks and buried mixed waste at numerous sites within the DOE complex. Preventing these wastes from entering the environment is a challenging task. One method of preventing waste migration is to isolate the contaminants using subsurface containment barriers. Isolation and containment can be accomplished by both in situ and ex situ methods. This report describes a novel in situ construction method of forming vertical containment barriers (slurry walls) using the SoilSaw{trademark} Barrier System. The SoilSaw{trademark} Barrier System is shown to be a feasible process for constructing subsurface vertical containment barriers to depths of fifty feet. The process is most efficient in sandy soil (including free flowing sand) with barrier construction rates of over 130 square feet per minute. Productivity diminishes to approximately 30 square feet per minute as soils become harder and more cohesive. The present hardware is designed to form a barrier of approximately 12 inch in width. Additional barrier widths can be constructed with this technology by application of wider jet heads. The requirement for a varied arrangement of barrier widths is an increase in hydraulic horse power and additional jet heads.

  7. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats.

    Science.gov (United States)

    Baracho, Nilo César do Vale; Arruda, Guilherme D'Andréa Saba; Alves, Lidinei José; Carneiro, Márcio Felipe Salomon; Siqueira, Matheus Teodoro Grilo; Arango, Héctor Gustavo; Marcos dos Reis, José

    2008-01-01

    High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR). Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. The use of generic drug and similars (A and B) drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.

  8. Flowsheet Validation For The Permanganate Digestion Of REILLEX(trademark) HPQ Anion Resin

    International Nuclear Information System (INIS)

    Kyser, E.

    2009-01-01

    The flowsheet for the digestion of Reillex(trademark) HPQ was validated both under the traditional alkaline conditions and under strongly acidic conditions. Due to difficulty in performing a pH adjustment in the large tank where this flowsheet must be performed, the recommended digestion conditions were changed from pH 8-10 to 8 M HNO 3 . Thus, no pH adjustment of the solution is required prior to performing the permanganate addition and digestion and the need to sample the digestion tank to confirm appropriate pH range for digestion may be avoided. Neutralization of the acidic digestion solution will be performed after completion of the resin digestion cycle. The amount of permanganate required for this type of resin (Reillex(trademark) HPQ) was increased from 1 kg/L resin to 4 kg/L resin to reduce the amount of residual resin solids to a minimal amount ( 2 ) solids (1.71 kg/L resin) and involves the generation of a significant liquid volume due to the low solubility of permanganate. However, since only two batches of resin (40 L each) are expected to be digested, the total waste generated is limited.

  9. CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats

    Directory of Open Access Journals (Sweden)

    Meregalli C

    2012-06-01

    Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective

  10. An investigation of the applicability of the new ion exchange resin, Reillex{trademark}-HPQ, in ATW separations. Milestone 4, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Ashley, K.R.; Ball, J.; Grissom, M.; Williamson, M.; Cobb, S.; Young, D.; Wu, Yen-Yuan J.

    1993-09-07

    The investigations with the anion exchange resin Reillex{trademark}-HPQ is continuing along several different paths. The topics of current investigations that are reported here are: The sorption behavior of chromium(VI) on Reillex{trademark}-HPQ from nitric acid solutions and from sodium hydroxide/sodium nitrate solutions; sorption behavior of F{sup {minus}} on Reillex{trademark}-HPQ resin in acidic sodium nitrate solution; sorption behavior of Cl{sup {minus}} on Reillex{trademark}-HPQ resin in acidic sodium nitrate solution; sorption behavior of Br{sup {minus}} on Reillex{trademark}-HPQ resin in acidic sodium nitrate solution; and the Honors thesis by one of the students is attached as Appendix II (on ion exchange properties of a new macroperous resin using bromide as the model ion in aqueous nitrate solutions).

  11. Higher incidence of injection site reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen.

    Science.gov (United States)

    Kamimura, Tomohiko; Miyamoto, Toshihiro; Yokota, Noriko; Takashima, Shuichiro; Chong, Yong; Ito, Yoshikiyo; Akashi, Koichi

    2013-02-01

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that injections of scBor should be rotated among eight different sites on the abdomen and thigh. However, detailed information about injection site reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor injections in ten patients, whereas grade 2 ISRs occurred following seven injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh injections but only in 1 of 93 (1.1%) abdominal injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next injection even if it occurs. © 2012 John Wiley & Sons A/S.

  12. High incidence and severity of injection site reactions in the first cycle compared with subsequent cycles of subcutaneous bortezomib.

    Science.gov (United States)

    Kamimura, Tomohiko; Miyamoto, Toshihiro; Yokota, Noriko; Aoki, Takatoshi; Ito, Yoshikiyo; Akashi, Koichi

    2013-12-01

    Subcutaneous (sc) administration of bortezomib (Bor) has become more common than intravenous (iv) administration in the treatment of multiple myeloma (MM), because scBor results in a lower incidence and severity of peripheral neuropathy and shows efficacy equivalent to ivBor. Bor is an irritant cytotoxic agent when it extravasates from the vasculature. Therefore, it is recommended that sc injections of Bor should be delivered on a rotating basis across eight sites on the abdomen and thighs. Previously, we reported that sc injections of Bor in the abdomen caused fewer grade 2 injection site reactions (ISRs) than those in the thigh. In the present study, we recruited more patients and expanded the scale of our analysis into ISRs following treatment with 300 scBor injections in 20 patients. ISRs of ≥grade 2 were documented in 12 of 109 (11.0 %) thigh injections, but only in three of 191 (1.6 %) abdominal injections (p ISRs of ≥grade 2 occurred more frequently in the first cycle than in the second and subsequent cycles (16.3 vs. 0.91 %, p ISR management, particularly with regard to the first cycle of scBor administration in the thigh. To our knowledge, this is the first report showing that ≥grade 2 ISRs are more common in the first cycle compared with subsequent cycles of scBor in the treatment of MM.

  13. HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Hongbiao Huang

    Full Text Available Combinations of proteasome inhibitors and histone deacetylases (HDAC inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21(cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like activity assay. Here we report that (i the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii the combination also synergistically inhibits tumor growth in vivo; (iii two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.

  14. Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation.

    Science.gov (United States)

    Chakraborty, R; Muchtar, E; Kumar, S K; Buadi, F K; Dingli, D; Dispenzieri, A; Hayman, S R; Hogan, W J; Kapoor, P; Lacy, M Q; Leung, N; Warsame, R; Kourelis, T; Gonsalves, W; Gertz, M A

    2018-03-01

    Post-transplant maintenance is widely used in multiple myeloma (MM); however, there is a lack of data on real-world outcomes. We have analyzed 577 patients with newly diagnosed MM undergoing early auto-transplantation between 2010 and 2015. A total of 341, 132 and 104 patients received no, lenalidomide (Len) or bortezomib (Bort) maintenance, respectively. Patients receiving Len or Bort maintenance had a higher incidence of high-risk cytogenetics by fluorescence in situ hybridization (31% (Len) vs 58% (Bort) vs 8% (No); Pmaintenance led to a superior progression-free survival (PFS) compared with no maintenance (median, 37 vs 28 months, respectively; P=0.002; adjusted hazard ratio 0.48 (95% CI, 0.35-0.66)), including in subgroups with ISS stage III disease (median, 40 vs 24 months; P=0.008) and high-risk cytogenetics (median, 27 vs 16 months; P=0.032). Bort maintenance did not confer PFS benefit for the entire cohort, but improved PFS in the high-risk cytogenetic subgroup (median, 28 vs 16 months; P=0.035). Discontinuation due to toxicity was seen in 17 and 7% of patients receiving Len or Bort maintenance, respectively. Our results indicate that post-transplant maintenance with Len or Bort is well tolerated in clinical practice and improves PFS in high-risk subgroups of MM patients.

  15. Change in ploidy status from hyperdiploid to near-tetraploid in multiple myeloma associated with bortezomib/lenalidomide resistance.

    Science.gov (United States)

    Pavlistova, Lenka; Zemanova, Zuzana; Sarova, Iveta; Lhotska, Halka; Berkova, Adela; Spicka, Ivan; Michalova, Kyra

    2014-01-01

    Ploidy is an important prognostic factor in the risk stratification of multiple myeloma (MM) patients. Patients with MM can be divided into two groups according to the modal number of chromosomes: nonhyperdiploid (NH-MM) and hyperdiploid (H-MM), which has a more favorable outcome. The two ploidy groups represent two different oncogenetic pathways determined at the premalignant stage. The ploidy subtype also persists during the course of the disease, even during progression after the therapy, with only very rare cases of ploidy conversion. The clinical significance of ploidy conversion and its relation to drug resistance have been previously discussed. Here, we describe a female MM patient with a rare change in her ploidy status from H-MM to NH-MM, detected by cytogenetic and molecular cytogenetic examinations of consecutive bone marrow aspirates. We hypothesize that ploidy conversion (from H-MM to NH-MM) is associated with disease progression and acquired resistance to bortezomib/lenalidomide therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma.

    Science.gov (United States)

    de la Puente, Pilar; Luderer, Micah J; Federico, Cinzia; Jin, Abbey; Gilson, Rebecca C; Egbulefu, Christopher; Alhallak, Kinan; Shah, Shruti; Muz, Barbara; Sun, Jennifer; King, Justin; Kohnen, Daniel; Salama, Noha Nabil; Achilefu, Samuel; Vij, Ravi; Azab, Abdel Kareem

    2018-01-28

    The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells. Our goal was to test CD38 targeted chitosan NPs as novel targeting moiety for MM to improve the potency and efficacy of BTZ in MM cells and reduce the side effects in healthy tissue. We have showed preferential BTZ release in tumor-microenvironment, specific binding to MM cells, and an improved drug cellular uptake through BTZ diffusion from the surface and endocytosed NPs, which translated in enhanced proteasome inhibition and robust cytotoxic effect on MM cells when BTZ was administered through anti-CD38 chitosan NPs. Furthermore, the anti-CD38 chitosan NPs specifically delivered therapeutic agents to MM cells improving therapeutic efficacy and reducing side effects in vivo. The anti-CD38 chitosan NPs showed low toxicity profile allowing enhancement of proteasome-inhibitory activity and specificity of BTZ by endocytosis-mediated uptake of CD38 representing a promising therapy in MM. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Bortezomib for acute humoral rejection treatment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City: an update.

    Science.gov (United States)

    Leyva, Sergio; Marino, Lluvia A; Alberú, Josefina; Morales-Buenrostro, Luis E

    2010-01-01

    The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response, or to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will be necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal. Until now, it is evident that many patients needed retreatment and they were well tolerated.

  18. How Shorebilly Brewing Company Won the Trademark Battle, but Lost the War: A Cautionary Tale for Entrepreneurs

    Science.gov (United States)

    Koval, Michael R.

    2018-01-01

    This article demonstrates how the case at hand, Teal Bay Alliances, LLC v. Southbound One, Inc., can be used as the core of a business case to teach students not only the basics of trademark law, but also as a real-world cautionary tale whose moral boils down to this: lawyers and businesspeople approach legal disputes from very different…

  19. 16 CFR 301.43 - Use of deceptive trade or corporate names, trademarks or graphic representations prohibited.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Use of deceptive trade or corporate names... Regulations § 301.43 Use of deceptive trade or corporate names, trademarks or graphic representations prohibited. No person shall use in labeling, invoicing or advertising any fur or fur product a trade name...

  20. This Bud's for You: Understanding International Intellectual Property Law through the Ongoing Dispute over the Budweiser Trademark

    Science.gov (United States)

    Bird, Robert C.

    2006-01-01

    There is little doubt that topics related to beer would be of some interest to college students. Anheuser-Busch, well known for its Budweiser beer and humorous advertising, faces a global trademark challenge to its "Budweiser" name. This battle between a global American company and a small Czech brewery is an opportunity for interesting…

  1. 77 FR 3745 - Establishment of a One-Year Retention Period for Trademark-Related Papers That Have Been Scanned...

    Science.gov (United States)

    2012-01-25

    ... That Have Been Scanned Into the Trademark Initial Capture Registration System AGENCY: United States... disposal would otherwise have occurred. The one-year retention period for papers scanned into TICRS will... papers that have been scanned into TICRS. See Request for Comments on Establishment of a One-Year...

  2. Recognition of Grouping Patterns in Trademarks Based on the Gestalt Psychology

    Science.gov (United States)

    Iguchi, Hiromasa; Abe, Koji; Misawa, Tadanobu; Kimura, Haruhiko; Daido, Yoshimasa

    According to the Gestalt principals, in this paper, we model features for measuring the attraction degree between couples of image components, and grouping areas in trademark images are recognized. This investigation would be used for content-based image retrieval from the view of mirroring human perception for images. The features of proximity, shape similarity, closure, and good continuation are extracted from every combination of two components in an image. After that, according to results of the judgments, a grouping pattern for the query is fixed. Besides, changing combination of the features, the proposed method can output plural grouping patterns. In the experiments, we have evaluated the proposed method on 74 test images comparing between outputs by the proposed method and grouping patterns for the test images obtained from results of questionnaires by 104 participants.

  3. GlidCop {sup trademark} DSC properties in the temperature range of 20-350 C

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, R.R. [SCM Metal Products, Inc., Research Triangle Park, NC (United States); Troxell, J.D. [SCM Metal Products, Inc., Research Triangle Park, NC (United States); Nadkarni, A.V. [SCM Metal Products, Inc., Research Triangle Park, NC (United States)

    1996-10-01

    GlidCop {sup trademark} AL-25 LOX-80 grade plates manufactured by processes relevant to ITER first wall copper alloy requirements were tested in the temperature range of 20-350 C. Plate manufacturing methods included hot isostatic pressing (HIP), extrusion (EXT), and extrusion followed by cross-rolling (EXT+XROLL). Tests that were performed included tensile, fracture toughness, impact toughness, and creep. The EXT+XROLL plate was found to have higher total elongation, reduction of area, and fracture toughness values than the EXT and HIP plates. All three processes had similar ultimate tensile and 0.2% yield strengths. The HIP material exhibited a lower creep rate than EXT+XROLL. The EXT and the EXT+XROLL plates had similar impact toughness values, which were higher than the HIP plate. Overall, the EXT+XROLL plate had the best combination of properties of the three processes examined. (orig.).

  4. The Community Trademark and the Office for Harmonization on the Internal Market (OHIM

    Directory of Open Access Journals (Sweden)

    Cornel Grigorut

    2012-05-01

    Full Text Available The registration of products and services through the Community trade mark give them anextended protection, acceptable throughout the European Union (EU. By means of a single registration,protection is obtained in all the 27 Member States and the previously recorded Community trademarks orthose presented for registration automatically extend their effects in the countries that will join the EuropeanUnion. The advantage of registering a Community trade mark is highlighted by minimal registration costs,extended protection across the EU and a minimal time to become legal, for the benefit of exporters and ofthose providing services, in order to avoid divergence (payment of damages and conflicts with thecompanies and businesses in this area.

  5. Eichrom's ABEC trademark resins: Alkaline radioactive waste treatment, radiopharmaceutical, and potential hydrometallurgical applications

    International Nuclear Information System (INIS)

    Bond, A.H.; Gula, M.J.; Chang, F.; Rogers, R.D.

    1997-01-01

    Eichrom's ABEC trademark resins selectivity extract certain anions from high ionic strength acidic, neutral, or strongly alkaline media, and solute stripping can be accomplished by eluting with water. ABEC resins are stable to pH extreme and radiolysis and operate in high ionic strength and/or alkaline solutions where anion-exchange is often ineffective. Potential applications of the ABEC materials include heavy metal and ReO 4 - separations in hydrometallurgy and purification of perrhenate iodide, and iodate in radiopharmaceutical production. Separation of 99m TcO 4 - from its 99 MoO 4 2- parent and stripping with water or physiological saline solution have been demonstrated for radiopharmaceutical applications. Removal of 99 TcO 4 - and 129 I - from alkaline tank wastes has also been successfully demonstrated. The authors will discuss the scale-up studies, process-scale testing, and market development of this new extraction material

  6. Integration of MATLAB Simulink(Registered Trademark) Models with the Vertical Motion Simulator

    Science.gov (United States)

    Lewis, Emily K.; Vuong, Nghia D.

    2012-01-01

    This paper describes the integration of MATLAB Simulink(Registered TradeMark) models into the Vertical Motion Simulator (VMS) at NASA Ames Research Center. The VMS is a high-fidelity, large motion flight simulator that is capable of simulating a variety of aerospace vehicles. Integrating MATLAB Simulink models into the VMS needed to retain the development flexibility of the MATLAB environment and allow rapid deployment of model changes. The process developed at the VMS was used successfully in a number of recent simulation experiments. This accomplishment demonstrated that the model integrity was preserved, while working within the hard real-time run environment of the VMS architecture, and maintaining the unique flexibility of the VMS to meet diverse research requirements.

  7. Development of the SEAtrace{trademark} barrier verification and validation technology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, S.D.; Lowry, W.; Walsh, R.; Rao, D.V. [Science and Engineering Associates, Santa Fe, NM (United States); Williams, C. [Sandia National Labs., Albuquerque, NM (United States). Underground Storage Technology Dept.

    1998-08-01

    In-situ barrier emplacement techniques and materials for the containment of high-risk contaminants in soils are currently being developed by the Department of Energy (DOE). Because of their relatively high cost, the barriers are intended to be used in cases where the risk is too great to remove the contaminants, the contaminants are too difficult to remove with current technologies, or the potential movement of the contaminants to the water table is so high that immediate action needs to be taken to reduce health risks. Assessing the integrity of the barrier once it is emplaced, and during its anticipated life, is a very difficult but necessary requirement. Science and Engineering Associates, Inc., (SEA) and Sandia National Laboratories (SNL) have developed a quantitative subsurface barrier assessment system using gaseous tracers in support of the Subsurface Contaminants Focus Area barrier technology program. Called SEAtrace{trademark}, this system integrates an autonomous, multi-point soil vapor sampling and analysis system with a global optimization modeling methodology to locate and size barrier breaches in real time. The methodology for the global optimization code was completed and a prototype code written using simplifying assumptions. Preliminary modeling work to validate the code assumptions were performed using the T2VOC numerical code. A multi-point field sampling system was built to take soil gas samples and analyze for tracer gas concentration. The tracer concentration histories were used in the global optimization code to locate and size barrier breaches. SEAtrace{trademark} was consistently able to detect and locate leaks, even under very adverse conditions. The system was able to locate the leak to within 0.75 m of the actual value, and was able to determine the size of the leak to within 0.15 m.

  8. Areva's Actiflo trademark -Rad water treatment system for the Fukushima nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Prevost, Thierry; Blase, Michael [AREVA NC, Paris (France); Paillard, Herve [Veolia Water, Saint Maurice (France); Mizuno, Hisamatsu [Veolia Water Japan, Tokyo (Japan)

    2012-05-15

    In the wake of the March 11{sup th} 2011 earthquake and tsunami and the subsequent flooding of several of the Fukushima Daiichi reactor units, Japan and the Japanese utility Tepco faced a crisis situation with incredible challenges. Sea water and later desalted sea water used for open circuit post-accident reactor cooling accumulated in the basements of four reactor buildings as well as in the basements of the turbine buildings on the site. The water had been heavily contaminated due to the fact that it had been in contact with molten fuel assemblies in the reactor cores. The water from flooding and subsequent cooling needed to be collected, along with rainwater. Despite the use of additional water storage systems brought to the site, a shortage of water storage capacity was expected in a 3-month timeframe, especially in view of the coming rain season in Japan. The overall water inventory was estimated at around 110,000 tons with a contamination up to the order of 1 Ci/l (3.7 x 10{sup 10} Bq/l). To avoid an over-flow of highly contaminated water into the sea Tepco envisaged establishing a water treatment system. This article focuses on the Actiflo trademark -Rad water treatment project implemented by Areva as part of the Tepco general water treatment scheme. It presents a detailed look at the functional principle of the Actiflo trademark -Rad process, related on-the-fly research and development, an explanation of system implementation challenges and a brief summary of operation results. (orig.)

  9. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine.

    Directory of Open Access Journals (Sweden)

    Saurabh Bundela

    Full Text Available Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine.

  10. Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model.

    Science.gov (United States)

    Bruna, Jordi; Alé, Albert; Velasco, Roser; Jaramillo, Jessica; Navarro, Xavier; Udina, Esther

    2011-09-01

    Pre-existing neuropathy, a not uncommon feature in oncologic patients, is a potential but non-confirmed risk factor to develop early or severe chemotherapy-induced neuropathy. The main goal of this study is to evaluate the role of pre-existing neuropathy induced by vincristine (VNC) or bortezomib (BTZ) as a risk factor to develop more severe BTZ-induced neuropathy in a mouse model. VNC, at doses of 1 and 1.5 mg/kg given twice per week for 4 weeks, induced a moderate and severe sensory-motor neuropathy, primarily axonal, with predominant involvement of myelinated sensory axons. The neuropathy induced by BTZ at dose of 1 mg/kg given twice per week for 6 weeks was a mild axonal sensory neuropathy involving myelinated and unmyelinated fibers. The neuropathy in mice previously treated and retreated with the same schedule of BTZ after 4 weeks of washout period was similar in profile and severity to the one observed after the first treatment. When basal neuropathy was classified as moderate (most of BTZ-treated animals) or severe (all VNC-treated animals and two BTZ-treated animals), there was a more marked decline in sensory nerve function during BTZ retreatment in the group with basal severe neuropathy (-86%) than in the groups with basal mild (-57%) or without neuropathy (-52%; p < 0.001). Histopathological findings supported the functional results. Therefore, this study shows that the presence of a severe neuropathy previous to treatment with an antitumoral agent, such as BTZ, results in a more marked involvement of peripheral nerves. © 2011 Peripheral Nerve Society.

  11. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    Science.gov (United States)

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  12. Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial.

    Science.gov (United States)

    Einsele, Hermann; Engelhardt, Monika; Tapprich, Christoph; Müller, Jürgen; Liebisch, Peter; Langer, Christian; Kropff, Martin; Mügge, Lars O; Jung, Wolfram; Wolf, Hans-Heinrich; Metzner, Bernd; Hart, Christina; Gramatzki, Martin; Hertenstein, Bernd; Pfreundschuh, Michael; Rösler, Wolf; Fischer, Thomas; Maschmeyer, Georg; Kanz, Lothar; Hess, Georg; Jäger, Elke; Bentz, Martin; Dürk, Heinz A; Salwender, Hans; Hebart, Holger; Straka, Christian; Knop, Stefan

    2017-11-01

    We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55·5 months); median progression-free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P < 0·0001), and median OS was 54·7 months versus not reached (P = 0·0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long-term follow-up, cytogenetic high risk is associated with markedly reduced PFS and OS post-ASCT. © 2017 John Wiley & Sons Ltd.

  13. Weldability of superalloys alloy 718 and ATI {sup registered} 718Plus trademark. A study performed by Varestraint testing

    Energy Technology Data Exchange (ETDEWEB)

    Jacobsson, Jonny [The Production Technology Centre Univ. West, Trollhaettan (Sweden). GKN Aerospace Sweden; Chalmers Univ. of Technology, Gothenburg (Sweden). Dept. of Industrial and Material Science; Andersson, Joel [The Production Technology Centre Univ. West, Trollhaettan (Sweden). Dept. of Engineering Science; Brederholm, Anssi; Haenninen, Hannu [Aalto Univ., Helsinki (Finland). Dept. of Engineering Design and Production

    2017-11-01

    In this study, the old and well-known alloy 718 is compared with the newly developed ATI {sup registered} 718Plus trademark from the weldability point of view. This is done in order to gain new information that have not been documented and established yet among the high-temperature materials with high strength, oxidation resistance, thermal stability and sufficient weldability, yet. ATI {sup registered} 718Plus trademark shows a lower sensitivity to hot cracking than alloy 718 with approximately 10 mm total crack length (TCL) difference in Varestraint testing. In the solution-annealed condition at 982 C for 4.5 h followed by air cooling, the crack sensitivity is decreased as compared to the mill-annealed condition. Along the crack path and also ahead of the crack tip, γ-Laves eutectic is present in both alloys. The microhardness measurements showed similar hardness level of 250 HV in the weld metal of both alloys and even in the parent material of alloy 718. ATI {sup registered} 718Plus trademark parent metal had hardness of 380 HV and a small increase of less than 50 HV was observed for both studied alloys in the heat affected zone (HAZ). For the same grain size of ATI {sup registered} 718Plus trademark (8.3 μm) and alloy 718 (15.6 μm), the susceptibility to liquation cracking may increase with increasing grain size. With a small grain size, there is a possibility to accommodate more trace elements (B, S, P) due to the larger grain boundary area. The impurity elements were found in relatively small precipitates, typically borides (0.2 μm), phosphides (0.1 to 0.5 μm) and carbo-sulphides. The solidification sequence of alloy 718 and ATI {sup registered} 718Plus trademark is relatively similar, where the liquid starts to solidify as γ-phase followed by γ/MC reaction at about 1260 C and then final γ/Laves eutectic reaction at around 1150 C. Detailed knowledge about weldability of alloy 718 and ATI {sup registered} 718Plus trademark can be used for material

  14. Synergistic interaction between the novel histone deacetylase inhibitor ST2782 and the proteasome inhibitor bortezomib in platinum-sensitive and resistant ovarian carcinoma cells.

    Science.gov (United States)

    Gatti, Laura; Benedetti, Valentina; De Cesare, Michelandrea; Corna, Elisabetta; Cincinelli, Raffaella; Zaffaroni, Nadia; Zunino, Franco; Perego, Paola

    2012-08-01

    The ability of histone deacetylase inhibitors to modulate the expression of genes relevant for growth or apoptotis regulation supports their interest in combination treatments of resistant tumors. We explored the effect of the combination of the histone deacetylase inhibitor ST2782 and the proteasome inhibitor bortezomib in ovarian carcinoma cell lines, including the IGROV-1 cell line and two p53 mutant platinum-resistant sublines (IGROV-1/OHP and IGROV-1/Pt1). We found a synergistic interaction between the two drugs, more evident in the p53-mutant resistant sublines, which was associated with increa sed apoptosis. The treatment with ST2782 resulted in early induction of Bax as well as in cleavage of caspase 3 and poly (ADP-ribose) polymerase only in the resistant cell lines. The inhibition of p53-transcriptional transactivation by pifithrin alpha in IGROV-1 cells enhanced the synergism. Conversely, knockdown of endogenous wild-type p53 in IGROV-1 cells determined synergism reduction. These opposite effects support the relevance of the transactivation-deficient mutant p53 as a synergism determinant. Moreover, in vivo studies indicated that tumor growth inhibition tended to be more evident in mice receiving the drug combination than in those treated with bortezomib alone. Overall, our study supports the potential effectiveness of the combination in platinum drug-resistant ovarian cancer carrying mutant p53. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

    Directory of Open Access Journals (Sweden)

    Bappa Adamu

    2016-01-01

    Full Text Available Light chain deposition disease (LCDD is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

  16. Successful treatment of severe immune hemolytic anemia after allogeneic stem cell transplantation with bortezomib: report of a case and review of literature.

    Science.gov (United States)

    Hosoba, Sakura; Jaye, David L; Cohen, Cynthia; Roback, John D; Waller, Edmund K

    2015-02-01

    Immune hemolytic anemia is a well-known complication after allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant hemolytic anemia results in increased red blood cell transfusions and medical sequelae including iron overload. We present a case report of immune hemolytic anemia that occurred after allogeneic HSCT from an ABO major-mismatched, HLA-matched unrelated donor. The patient had high anti-donor A type antibodies that were unresponsive to treatment with steroids and rituximab, resulting in persistent transfusion dependence. A detailed time course of anti-A titers, plasma cell content of the marrow, and B-cell content of the blood is presented. Treatment with bortezomib, a protease inhibitor, eliminated residual host-type plasma cells secreting anti-A and restored normal donor-derived erythropoiesis. This report, and a review of literature for treatment of immune hemolytic anemia after allogeneic HSCT, supports the utility of bortezomib as plasma cell-targeted therapy in this setting. © 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  17. New Rising Infection: Human Herpesvirus 6 Is Frequent in Myeloma Patients Undergoing Autologous Stem Cell Transplantation after Induction Therapy with Bortezomib

    Directory of Open Access Journals (Sweden)

    Netanel Horowitz

    2012-01-01

    Full Text Available Herpesvirus 6 (HHV-6 infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM patients undergoing autologous stem cell transplantation (ASCT after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD (; 66% or thalidomide-dexamethasone (TD (, 34% induction, together with melphalan 200 mg/m2 autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%, accounting for 35% of those screened; its incidence was 19.5% ( in the VD group versus 9.5% ( in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

  18. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2010-11-01

    Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

  20. Green Nanotechnology for Synthesis and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) nanoparticles for sustained bortezomib release using supercritical CO2 assisted particle formation combined with electrodeposition.

    Science.gov (United States)

    Demirdöğen, Ruken Esra; Emen, Fatih Mehmet; Ocakoglu, Kasim; Murugan, Paramasivam; Sudesh, Kumar; Avşar, Göktürk

    2018-02-01

    Carbon dioxide assisted particle formation combined with electrospraying using supercritical CO 2 (scCO 2 ) as an aid (Carbon Dioxide Assisted Nebulization-Electrodeposition, CAN-ED) was used to produce Bortezomib loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) nanoparticles for sustained release. The morphology and structure of the prepared nanoparticles were investigated by SEM, TEM and FT-IR spectroscopy. Average diameter of particles obtained was 155nm and the average core sizes of P(3HB-co-3HHx) nanoparticles were between 6 and 13nm. The drug loading capacity, drug release and stability of Bortezomib loaded P(3HB-co-3HHx) nanoparticles were analyzed. The maximum loading capacity was achieved at pH=6.0 in phosphate buffer (K 2 HPO 4 /KH 2 PO 4 ). It was found that temperature did not affect the stability of Bortezomib loaded nanoparticles and it was good both at 37°C and 4°C. This study pointed out that CAN-ED is a green method to produce P(3HB-co-3HHx) nanoparticles for pH responsive targeting of Bortezomib especially to parts of the body where size exclusion is not crucial. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Comparative Advertisements in the Business World: Need for Interplay of Trademark Law, Consumer Law and Competition Law

    OpenAIRE

    Sreenivasulu, Neeruganti Shanmuka

    2018-01-01

    Comparative advertisements also known as disparaging advertisements are regulated for the purpose of ensuring that nobody should negatively portray or present the competitors goods, and services or image and reputation in the business world. Though trademarks serve the purpose of identifying, representing and also advertising the brand of the business, business world often aims to reach out to the consumer through audiovisual means such as advertisements. Audiovisual advertisements would attr...

  2. Use of in-situ Dual Vacuum Extraction trademark for remediation of soil and ground water

    International Nuclear Information System (INIS)

    Dodson, M.E.; Trowbridge, B.E.; Ott, D.

    1994-01-01

    Dual Vacuum Extraction trademark provides a rapid and cost-effective method of remediating soil and ground water contaminated with volatile organic compounds. The system involves the removal of both water and vapors through the same borehole by use of entrainment. This technology provides for the remediation of the vadose zone, capillary fringe, smear zone, and existing water table. The effectiveness of this technology is shown in a case study. A release from an underground storage tank was responsible for a hydrocarbon plume spreading over approximately 50,000 ft 2 . The release produced vadose-zone contamination in the silty and sandy clays from 10 to 30 ft below ground surface (bgs) with total petroleum hydrocarbon (TPH) concentrations up to 1,400 mg/kg. In addition, a layer of free-floating liquid hydrocarbon was present on a shallow aquifer located at 25 ft bgs in thicknesses ranging from 0.5 to 3.0 ft. An in-situ dual-extraction system was installed to remediate the soils and ground water to levels as required by the Los Angeles Regional Water Quality Control Board (RWQCB). The system operated 24 hr a day, with an operating efficiency of over 99%. After 196 days (28 weeks), over 17,000 lb of hydrocarbons had been extracted from the soils. Seven confirmatory soil borings in the area of highest initial hydrocarbon concentrations indicated that TPH and benzene, toluene, ethylbenzene, xylene (BTEX) concentrations had decreased over 99% from initial soil concentrations

  3. Performance evaluation of the PITBULL{trademark} pump for the removal of hazardous waste

    Energy Technology Data Exchange (ETDEWEB)

    Hatchell, B.K.; Combs, W.H.; Hymas, C.R.; Powell, M.R.; Rinker, M.W.; White, M.

    1998-09-01

    One objective of the Waste Removal Project at the Department of Energy`s Savannah River Site (SRS) is to explore methods to successfully remove waste heels that will remain in the high-level waste tanks after bulk waste removal has been completed. Tank closure is not possible unless this residue is removed. As much as 151,000 liters of residue can remain after a conventional waste removal campaign. The waste heels can be comprised of sludge, zeolite, and silica. The heels are generally hardened or compacted insoluble particulate with relatively rapid settling velocities. A PITBULL{trademark} pump is being considered by SRS to retrieve sludge-type waste from Tank 19. Sections 1 through 4 of this report present the scope and objectives of the test program, describe the principles of operation of the PITBULL, and present the test approach, set-up, and instrumentation. Test results, including pumping rates with water and slurry, are provided in Section 5, along with considerations for remote operation. Conclusions and recommendations are provided in Section 6.

  4. Final environmental assessment for the Liquid Phase Methanol (LPMEOH trademark) Project

    International Nuclear Information System (INIS)

    1995-06-01

    The proposed project is to demonstrate on a commercial scale the production of methanol from coal-derived synthesis gas using the LPMEOH trademark process. The methanol produced during this demonstration will be used as a chemical feedstock (on-site) and/or as an alternative fuel in stationary and transportation applications (off-site). In addition, the production of dimethyl ether (DME) as a mixed co-product with methanol may be demonstrated for a six month period under the proposed project pending the results of laboratory/pilot-scale research on scale-up. The DME would be used as fuel in on-site boilers. The proposed LPMEOH facility would occupy approximately 0.6 acres of the 3,890-acre Eastman Chemical facility in Kingsport, TN. The effects of the proposed project include changes in air emissions, wastewater discharge, cooling water discharge, liquid waste quantities, transportation activities, socioeconomic effects, and quantity of solids for disposal. No substantive negative impacts or environmental concerns were identified

  5. Characterization of radioactive contamination inside pipes with the Pipe Explorer trademark system

    International Nuclear Information System (INIS)

    Lowry, W.

    1994-01-01

    The objective for the development of the Pipe Explorer trademark radiological characterization system is to achieve a cost effective, low risk means of characterizing gamma radioactivity on the inside surface of pipes. The unique feature of this inspection system is the use of a pneumatically inflated impermeable membrane which transports the detector into the pipe as it inverts. The membrane's internal air pressure tows the detector and tether through the pipe. This mechanism isolates the detector and its cabling from the contaminated surface, yet allows measurement of radioactive emissions which can readily penetrate the thin plastic membrane material (such as gamma and high energy beta emissions). In Phase 1, an initial survey of DOE facilities was conducted to determine the physical and radiological characteristics of piping systems. The inverting membrane deployment system was designed and extensively tested in the laboratory. A range of membrane materials was tested to evaluate their ruggedness and deployment characteristics. Two different sizes of gamma scintillation detectors were procured and tested with calibrated sources. Radiation transport modeling evaluated the measurement system's sensitivity to detector position relative to the contaminated surface, the distribution of the contamination, background gamma levels, and gamma source energy levels. In the culmination of Phase 1, a field demonstration was conducted at the Idaho National Engineering Laboratory's Idaho Chemical Processing Plant. The project is currently in transition from Phase 1 to Phase 2, where more extensive demonstrations will occur at several sites. Results to date are discussed

  6. Bioremediation of soils and sediments containing PAHs and PCP using Daramend trademark

    International Nuclear Information System (INIS)

    Seech, A.; Burwell, S.; Marvan, I.

    1994-01-01

    A full-scale demonstration of Grace Dearborn's Daramend trademark for bioremediation of soil containing chlorinated phenols, PAHs and petroleum hydrocarbons is being conducted at an industrial wood treatment site in Ontario. A pilot-scale demonstration of Daramend for the clean-up of sediments contaminated with PAHs was also conducted. The full-scale demonstration, which includes bioremediation of approximately 4,500 m 3 of soil, was initiated at a wood preserving facility in Ontario, in the summer of 1993. The soil contains chlorinated phenols, PAHs and total petroleum hydrocarbons at concentrations of up to 700, 1,400 and 6,300 mg/kg respectively. Full-scale bioremediation at this site employs the same Daramend protocols and organic amendment treatments that were used at the pilot-scale phase where the PAH, total petroleum hydrocarbon, and pentachlorophenol concentrations were reduced to below the Canadian clean-up guidelines for industrial soils. In addition, the toxicity of the soil to earthworms was eliminated while the rate of seed germination was increased to that of an agricultural soil during the pilot scale demonstration phase. The ex-situ portion of the full-scale demonstration is currently being audited by the EPA under the SITE program. This paper will focus on the ex-situ work. The pilot-scale demonstration of sediment remediation consisted of ex-situ bioremediation of approximately 90 tonnes of PAH-contaminated sediment in a confined treatment area

  7. Qualification of Reillex{trademark} HPQ anion exchange resin for use in SRS processes

    Energy Technology Data Exchange (ETDEWEB)

    Crooks, W.J. III

    2000-05-18

    The Phase 2 portion of the HB-Line facility was built in the early 1980's to process plutonium and neptunium from nitric acid solutions into oxide suitable for storage in a vault. Although the other portions of HB-Line were started up in the mid 1980's and have operated since that time, the anion exchange and precipitation processes in Phase 2 were never started up. As part of the material stabilization efforts, Phase 2 is currently being started up. A new anion exchange resin is needed because the resins that were proposed for use 10 years ago are limited by performance characteristics, disposal requirements, or are no longer commercially available. SRTC is responsible for qualifying all resins prior to their use in Nuclear Materials Stabilization and Storage (NMSS) processes. Qualification consists of both process suitability and thermal stability with nitric acid. This report describes the thermal stability qualification of Reillex{trademark} HPQ, the new resin proposed for processing plutonium and neptunium in the HB Line facility.

  8. Savings estimates for the ENERGY STAR (registered trademark) voluntary labeling program: 2001 status report

    Energy Technology Data Exchange (ETDEWEB)

    Webber, Carrie A.; Brown, Richard E.; Mahajan, Akshay; Koomey, Jonathan G.

    2002-02-15

    ENERGY STAR(Registered Trademark) is a voluntary labeling program designed to identify and promote energy-efficient products, buildings and practices. Operated jointly by the Environmental Protection Agency (EPA) and the U.S. Department of Energy (DOE), ENERGY STAR labels exist for more than thirty products, spanning office equipment, residential heating and cooling equipment, commercial and residential lighting, home electronics, and major appliances. This report presents savings estimates for a subset of ENERGY STAR program activities, focused primarily on labeled products. We present estimates of the energy, dollar and carbon savings achieved by the program in the year 2000, what we expect in 2001, and provide savings forecasts for two market penetration scenarios for the period 2001 to 2020. The target market penetration forecast represents our best estimate of future ENERGY STAR savings. It is based on realistic market penetration goals for each of the products. We also provide a forecast under the assumption of 100 percent market penetration; that is, we assume that all purchasers buy ENERGY STAR-compliant products instead of standard efficiency products throughout the analysis period.

  9. SmartShelf{trademark}: Report of activities for fiscal year 1997

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Z.W.; Lawson, R.L.

    1997-09-26

    This report covers activities relating to the SmartShelf{trademark} project during the period October 1, 1996, through September 30, 1997. During this year, project team members have advanced the state of both the hardware and software through a six-month-long test that exercised all hardware and nearly all software components. Second-generation node hardware was constructed and tested with the system and it was found that components supplied by Dallas Semiconductor did not meet the manufacturer`s specifications and were unstable. However, it was possible to work around this problem by rapidly redesigning the second-generation printed circuit board to use proven first-generation electronics and still fit inside the custom designed second-generation enclosure. Thus, the benefits realized by adopting the custom enclosure was not compromised. The software was improved by moving the user interface from modules developed with LabView to forms, queries, and reports developed with Microsoft Access and the structures of the software was modified to take better advantage of the dynamic data exchange (DDE) client-server architecture built into the Windows95 operating system and Access.

  10. Not a mystery. Inner containment of the pressurized water reactor (EPR trademark type)

    Energy Technology Data Exchange (ETDEWEB)

    Ostermann, Dirk; Wienand, Burkhard; Krumb, Christian [AREVA NP GmbH (Germany)

    2012-11-01

    The containment of the advanced pressurized water reactor EPR trademark type is developed on the basis of the French nuclear power plant operational experience and consists of - The reinforced outer containment structure, designed to withstand external hazards (e.g. APC), - The pre-stressed inner containment structure, designed to bear the loads resulting from internal hazards (LOCA), - The steel liner, designed to provide leak tightness resulting from internal hazards. The main advantage of the pre-stressed inner containment design is that the structure remains in linear-elastic behavior during the whole life-time. Even in case of postulated design accidents (LOCA) concrete tensile strains are strongly limited. Due to pre-stressing the concrete structure remains practically free of cracks. Due to pre-stressing the leak tightness ensuring steel liner, embedded into the inner concrete shell, is exposed to more favorable compression loads. In addition to detailed calculations several test programs have been performed to verify and confirm the predicted behavior in normal operation and in accident condition. (orig.)

  11. Resolution of thermal-hydraulic safety and licensing issues for the system 80+{sup {trademark}} design

    Energy Technology Data Exchange (ETDEWEB)

    Carpentino, S.E.; Ritterbusch, S.E.; Schneider, R.E. [ABB-Combustion Engineering, Windsor, CT (United States)] [and others

    1995-09-01

    The System 80+{sup {trademark}} Standard Design is an evolutionary Advanced Light Water Reactor (ALWR) with a generating capacity of 3931 MWt (1350 MWe). The Final Design Approval (FDA) for this design was issued by the Nuclear Regulatory Commission (NRC) in July 1994. The design certification by the NRC is anticipated by the end of 1995 or early 1996. NRC review of the System 80+ design has involved several new safety issues never before addressed in a regulatory atmosphere. In addition, conformance with the Electric Power Research Institute (EPRI) ALWR Utility Requirements Document (URD) required that the System 80+ plant address nuclear industry concerns with regard to design, construction, operation and maintenance of nuclear power plants. A large number of these issues/concerns deals with previously unresolved generic thermal-hydraulic safety issues and severe accident prevention and mitigation. This paper discusses the thermal-hydraulic analyses and evaluations performed for the System 80+ design to resolve safety and licensing issues relevant to both the Nuclear Stream Supply System (NSSS) and containment designs. For the NSSS design, the Safety Depressurization System mitigation capability and resolution of the boron dilution concern are described. Examples of containment design issues dealing with containment shell strength, robustness of the reactor cavity walls and hydrogen mixing under severe accident conditions are also provided. Finally, the overall approach used in the application of NRC`s new (NUREG-1465) radiological source term for System 80+ evaluation is described. The robustness of the System 80+ containment design to withstand severe accident consequences was demonstrated through detailed thermal-hydraulic analyses and evaluations. This advanced design to shown to meet NRC severe accident policy goals and ALWR URD requirements without any special design features and unnecessary costs.

  12. SOx-NOx-Rox Box{trademark} flue gas clean-up demonstration. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Babcock and Wilcox`s (B and W) SOx-NOx-Rox Box{trademark} process effectively removes SOx, NOx and particulate (Rox) from flue gas generated from coal-fired boilers in a single unit operation, a high temperature baghouse. The SNRB technology utilizes dry sorbent injection upstream of the baghouse for removal of SOx and ammonia injection upstream of a zeolitic selective catalytic reduction (SCR) catalyst incorporated in the baghouse to reduce NOx emissions. Because the SOx and NOx removal processes require operation at elevated gas temperatures (800--900 F) for high removal efficiency, high-temperature fabric filter bags are used in the baghouse. The SNRB technology evolved from the bench and laboratory pilot scale to be successfully demonstrated at the 5-MWe field scale. This report represents the completion of Milestone M14 as specified in the Work Plan. B and W tested the SNRB pollution control system at a 5-MWe demonstration facility at Ohio Edison`s R.E. Burger Plant located near Shadyside, Ohio. The design and operation were influenced by the results from laboratory pilot testing at B and W`s Alliance Research Center. The intent was to demonstrate the commercial feasibility of the SNRB process. The SNRB facility treated a 30,000 ACFM flue gas slipstream from Boiler No. 8. Operation of the facility began in May 1992 and was completed in May 1993. About 2,300 hours of high-temperature operation were achieved. The main emissions control performance goals of: greater than 70% SO{sub 2} removal using a calcium-based sorbent; greater than 90% NOx removal with minimal ammonia slip; and particulate emissions in compliance with the New Source Performance Standards (NSPS) of 0.03 lb/million Btu were exceeded simultaneously in the demonstration program when the facility was operated at optimal conditions. Testing also showed significant reductions in emissions of some hazardous air pollutants.

  13. Intravenous contrast medium application in elderly patients - evaluation of Iopentol (Imagopaque trademark 300)

    International Nuclear Information System (INIS)

    Rathsmann, P.; Jacobs, G.F.; Mueller, R.D.

    2004-01-01

    Purpose: We examined the subjective compatibility of elderly patients who received the intravenous contrast medium Iopentol (Imagopaque trademark 300). In addition, objective data were acquired to show possible interactions between contrast media and organ systems in old patients. Methods and materials: A CT scan with intravenous application of contrast media was performed on 132 patients ranging in age from 75 to 96 years. The patients were questioned about their individual sensations. In addition, blood pressure, creatinine and CT-densitometry were acquired as objective date. Results: The patients' individual sensations and clinical data show a very low rate of complications. Mild allergic reactions were noticed in two patients. No severe anaphylactic reactions were encountered. Statistically significant changes in blood pressure before and after administration of the contrast medium were not observed. The serum creatinine concentration was unchanged after application of contrast media. For CT-densitometry, the patients were divided into two groups, one group with patients 75-84 years and the other group with patients 85-96 years of age. CT-densitometry showed no age-related differences. The protocol of contrast administration resulted in excellent opacification of the examined regions, only the liver did not enhance in some cases before the opacification of the portal vein. Conclusion: It is shown that old age alone is no reason to withhold contrast media containing iodine when performing CT. For the evaluation of the liver, however, the peculiarities of old age have to be taken into account and the interval between injection of the contrast medium and beginning of the spiral-CT has to be extended. (orig.)

  14. Advanced Light Water Reactor Plants System 80+trademark Design Certification Program

    International Nuclear Information System (INIS)

    1993-01-01

    The purpose of this report is to provide a status of the progress that was made towards Design Certification of System 80+trademark during the US government's 1993 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW t (1350 MWe) Pressurized Water Reactor (PWR). The design consists of an essentially complete plant. It is based on evolutionary improvements to the Standardized System 80 nuclear steam supply system in operation at Palo Verde Units 1, 2, and 3, and the Duke Power Company P-81 balance-of-plant (BOP) that was designed and partially constructed at the Cherokee plant site. The System 80/P-81 original design has been substantially enhanced to increase conformance with the EPRI ALWR Utility Requirements Document (URD). Some design enhancements incorporated in the System 80+ design are included in the four units currently under construction in the Republic of Korea. These units form the basis of the Korean standardization program. The full System 80+ standard design has been offered to the Republic of China, in response to their recent bid specification. The ABB-CE Standard Safety Analysis Report (CESSAR-DC) was submitted to the NRC and a Draft Safety Evaluation Report was issued by the NRC in October 1992. CESSAR-DC contains the technical basis for compliance with the EPRI URD for simplified emergency planning. The Nuclear Steam Supply System (NSSS) is the standard ABB-Combustion Engineering two-loop arrangement with two steam generators, two hot legs and four cold legs each with a reactor coolant pump. The System 80+ standard plant includes a sperical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual containment

  15. Inhibition of nuclear factor-κB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Van Waes, Carter; Chang, Angela A.; Lebowitz, Peter F.; Druzgal, Colleen H.; Chen, Zhong; Elsayed, Yusri A.; Sunwoo, John B.; Rudy, Susan; Morris, John C.; Mitchell, James B.; Camphausen, Kevin; Gius, David; Adams, Julian; Sausville, Edward A.; Conley, Barbara A.

    2005-01-01

    Purpose: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-κB (NF-κB) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: The tolerability and response to bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-κB-modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-κB phospho-p65, apoptosis, and expression of NF-κB-modulated mRNAs were compared in serial biopsies from accessible tumors. Results: The maximally tolerated dose was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m 2 and 0.9 mg/m 2 /dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 h after 0.6 mg/m 2 was 32%, 16%, and 7% and after 0.9 mg/m 2 was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-κB activity, apoptosis, and expression of NF-κB-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-κB-modulated cytokines in 1 patient with a major tumor reduction. Conclusions: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m 2 and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-κB localization, apoptosis, and NF-κB-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation

  16. Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant

    Directory of Open Access Journals (Sweden)

    Majed M. Almaghrabi

    2017-01-01

    Full Text Available Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient’s partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.

  17. Immunoglobulin D multiple myeloma, plasma cell leukemia and chronic myelogenous leukemia in a single patient treated simultaneously with lenalidomide, bortezomib, dexamethasone and imatinib

    Directory of Open Access Journals (Sweden)

    Naveed Ali

    2016-03-01

    Full Text Available Multiple myeloma (MM is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

  18. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

    Science.gov (United States)

    Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

    2017-01-01

    Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

  19. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study.

    Directory of Open Access Journals (Sweden)

    Jennifer Vandooren

    Full Text Available Gelatinase B or matrix metalloproteinase-9 (MMP-9 (EC 3.4.24.35 is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM, the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2 activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations.

  20. Full-scale demonstration of low-NO{sub x} cell{trademark} burner retrofit. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Eckhart, C.F.; Kitto, J.B.; Kleisley, R.J. [and others

    1994-07-01

    The objective of the Low-NO{sub x} Cell{trademark}Burner (LNCB{trademark}) demonstration is to evaluate the applicability of this technology for reducing NO{sub x} emissions in full-scale, cell burner-equipped boilers. More precisely, the program objectives are to: (1) Achieve at least a 50% reduction in NO{sub x} emissions. (2) Reduce NO{sub x} with no degradation to boiler performance or life of the unit. (3) Demonstrate a technically and economically feasible retrofit technology. Cell burner equipped boilers comprise 13% of the Pre-New Source Performance Standards (NSPS) coal-fired generating capacity. This relates to 34 operating units generating 23,639 MWe, 29 of which are opposed wall fired with two rows of two-nozzle cell burners on each wall. The host site was one of these 29. Dayton Power & Light offered use of J.M. Stuart Station`s Unit No. 4 as the host site. It was equipped with 24, two-nozzle cell burners arranged in an opposed wall configuration. To reduce NO{sub x} emissions, the LNCB{trademark} has been designed to delay the mixing of the fuel and combustion air. The delayed mixing, or staged combustion, reduces the high temperatures normally generated in the flame of a standard cell burner. A key design criterion for the burner was accomplishing delayed fuel-air mixing with no pressure part modifications to facilitate a {open_quotes}plug-in{close_quotes} design. The plug-in design reduces material costs and outage time required to complete the retrofit, compared to installing conventional, internally staged low-NO{sub x} burners.

  1. Gamma Ray Imaging System (GRIS) GammaCam trademark. Final report, January 3, 1994 - May 31, 1996

    International Nuclear Information System (INIS)

    1996-01-01

    This report describes the activities undertaken during the development of the Gamma Ray Imaging System (GRIS) program now referred to as the GammaCam trademark. The purpose of this program is to develop a 2-dimensional imaging system for gamma-ray energy scenes that may be present in nuclear power plants. The report summarizes the overall accomplishments of the program and the most recent GammaCam measurements made at LANL and Estonia. The GammaCam is currently available for sale from AIL Systems as an off-the-shelf instrument

  2. Gamma Ray Imaging System (GRIS) GammaCam{trademark}. Final report, January 3, 1994--May 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    This report describes the activities undertaken during the development of the Gamma Ray Imaging System (GRIS) program now referred to as the GammaCam{trademark}. The purpose of this program is to develop a 2-dimensional imaging system for gamma-ray energy scenes that may be present in nuclear power plants. The report summarizes the overall accomplishments of the program and the most recent GammaCam measurements made at LANL and Estonia. The GammaCam is currently available for sale from AIL Systems as an off-the-shelf instrument.

  3. Company Slogan and a Vivid Image of a Trademark - as Main Components of a Strong Brand

    Directory of Open Access Journals (Sweden)

    Igor BELOSTECINIC

    2015-12-01

    Full Text Available Among other methods, good brand managers always affect clients and strengthen their fidelity to the brand by means of company advertising slogans and vivid images associated with this brand. Slogans may function as useful “levers” or “hooks” helping clients to understand the essence of a trademark and its peculiarity, as well as to nail in clients' minds the established image of a strong brand. One of the “hooks” attracting attention to brand and helping to nail it in a common man's mind – is a company (advertising slogan - short message or motto, which actively presents the key theme of the brand in general or of a certain advertising campaign, and contains substantial information, reflecting the essence of campaign's or product's marketing offer. One must admit that it is nice to recall favorite philosopher's aphorisms or sayings while getting up in the morning, and to whistle an aria from a renowned opera on your way to work. However, more often people sing unsophisticated verses about the “sign of a good taste” and get annoyed by a trivial call to “have a break” going round in their heads. This means that the advertisement of popular chocolate bars and drinks has hit its target. The main lever for success in generation of a positive and recognizable brand image - is the slogan and its graphic image in consumer's mind. Together with other brand components (logo, corporate colors, sound or music image a slogan generates the system of constant elements which ensure the brand's internal unity and are aimed at creation of exposure effect. To some extent, we all are “ad eaters” and are always capable of estimating an ad, even if it is at the level of feelings: whether we like it or not. So why a certain advertisement can make us smile, elicit good feelings and cause an urge to buy product/service that is being advertised, and another one - evokes disappointment and annoyance? The answer is obvious: the first one was

  4. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  5. Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Takashi Watanabe

    Full Text Available To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS-granulocyte-macrophage colony-stimulating factor (GM-CSF, LPS-CXCL chemokine 10 (CXCL10, LPS-CCL chemokine 4 (CCL4, phytohemagglutinin-CCL4, zymosan A (ZA-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test and non-parametric (unpaired Mann-Whitney test tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test and non-parametric (paired Wilcoxon test tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients.

  6. An efficient 2D 11B–11B solid-state NMR spectroscopy strategy for monitoring covalent self-assembly of boronic acid-derived compounds: the transformation and unique architecture of bortezomib molecules in the solid state

    Czech Academy of Sciences Publication Activity Database

    Brus, Jiří; Czernek, Jiří; Urbanová, Martina; Kobera, Libor; Jegorov, A.

    2017-01-01

    Roč. 19, č. 1 (2017), s. 487-495 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR(CZ) GA16-04109S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : NMR crystalography * bortezomib * solid-state self-assembly Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.123, year: 2016

  7. Application of foresight methods in applications for patents and trademarks in Spain; Aplicacion de metodos de prevision en las solicitudes de patentes y marcas en Espana

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo Nuchera, A.; Glabaly Marquez, S.

    2011-07-01

    Patent and trademark offices which run according to principles of new management have an inherent need for dependable forecasting data in planning capacity and service levels. The predictive approach adopted for the time series of Spanish patents and trademarks applications (1979-2009) has been the use of different techniques of time series prediction in a short-term time horizon. The methods used can be grouped into two specifics areas: regression models of trends and time series models advanced. The results of this study show that it is possible to model the series of patents and trademarks applications with different models, especially ARIMA, with satisfactory model adjustment and relatively low error. (Author) 33 refs.

  8. SunSine{trademark}300: Manufacture of an AC Photovoltaic Module; Final Report Phases I & II; 25 July 1995-30 June 1998

    Energy Technology Data Exchange (ETDEWEB)

    Kern, G.

    1999-03-22

    The purpose of this PVMaT subcontract was to establish manufacturing capability and enter commercial production with the SunSine{trademark}300 AC Module. This goal was achieved when production began in September 1997, first units were shipped in December 1997, and the pilot production of 109 units was completed in the spring of 1998. As of the completion of this PVMaT project, production capacity is 2500 units per year, which represents 627.5 kW AC {at} STC. This report provides the background of the development process that led to a commercial version of the SunSine{trademark}300; describes the SunSine{trademark}300 product, including theory of operation; provides a summary of all the significant test methods that were applied to prototypes of the product, with a summary of test results; and ends with a summary of the production process and a list of project sponsors who received units for evaluation.

  9. Tobacco industry argues domestic trademark laws and international treaties preclude cigarette health warning labels, despite consistent legal advice that the argument is invalid.

    Science.gov (United States)

    Crosbie, Eric; Glantz, Stanton A

    2014-05-01

    To analyse the tobacco industry's use of international trade agreements to oppose policies to strengthen health warning labels (HWLs). A review of tobacco industry documents, tobacco control legislation and international treaties. During the early 1990s, the tobacco industry became increasingly alarmed about the advancement of HWLs on cigarettes packages. In response, it requested legal opinions from British American Tobacco's law firms in Australia and England, Britain's Department of Trade and Industry and the World Intellectual Property Organisation on the legality of restricting and prohibiting the use of their trademarks, as embodied in cigarette packages. The consistent legal advice, privately submitted to the companies, was that international treaties do not shield trademark owners from government limitations (including prohibition) on the use of their trademarks. Despite receiving this legal advice, the companies publicly argued that requiring large HWLs compromised their trademark rights under international treaties. The companies successfully used these arguments as part of their successful effort to deter Canadian and Australian governments from enacting laws requiring the plan packaging of cigarettes, which helped delay large graphic HWLs, including 'plain' packaging, for over a decade. Governments should not be intimidated by tobacco company threats and unsubstantiated claims, and carefully craft HWL laws to withstand the inevitable tobacco industry lawsuits with the knowledge that the companies' own lawyers as well as authoritative bodies have told the companies that the rights they claim do not exist.

  10. SEAMIST trademark in-situ instrumentation and vapor sampling system applications in the Sandia Mixed Waste Landfill Integrated Demonstration program: Final report

    International Nuclear Information System (INIS)

    Williams, C.

    1995-09-01

    The Mixed Waste Landfill Integrated Demonstration was tasked with demonstrating innovative technologies for the cleanup of chemical and mixed waste landfills that are representive of sites occurring throughout the DOE complex and the nation. The SEAMIST trademark inverting membrane deployment system has been used successfully at the Mixed Waste Landfill Integrated Demonstration (MWLID) for multipoint vapor sampling, pressure measurement, permeability measurement, sensor integration demonstrations, and borehole lining. Several instruments were deployed inside the SEAMIST trademark-lined boreholes to detect metals, radionuclides, moisture, and geologic variations. The liner protected the instruments from contamination, maintained support of the uncased borehole wall, and sealed the total borehole from air circulation. Recent activities included the installation of three multipoint vapor sampling systems and sensor integration systems in 100-foot-deep vertical boreholes. A long term pressure monitoring program has recorded barometric pressure effects at depth with relatively high spatial resolution. The SEAMIST trademark system has been integrated with a variety of hydrologic and chemical sensors for in-situ measurements, demonstrating its versatility as an instrument deployment system that allows easy emplacement and removal. Standard SEAMIST trademark vapor sampling systems were also integrated with state-of-the-art volatile organic compound analysis technologies. The results and status of these demonstration tests are presented

  11. SEAMIST{trademark} in-situ instrumentation and vapor sampling system applications in the Sandia Mixed Waste Landfill Integrated Demonstration program: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. [Sandia National Labs., Albuquerque, NM (United States). Environmental Restoration Technologies; Lowry, W.; Cremer, D.; Dunn, S.D. [Science and Engineering Associates, Inc., Santa Fe, NM (United States)

    1995-09-01

    The Mixed Waste Landfill Integrated Demonstration was tasked with demonstrating innovative technologies for the cleanup of chemical and mixed waste landfills that are representive of sites occurring throughout the DOE complex and the nation. The SEAMIST{trademark} inverting membrane deployment system has been used successfully at the Mixed Waste Landfill Integrated Demonstration (MWLID) for multipoint vapor sampling, pressure measurement, permeability measurement, sensor integration demonstrations, and borehole lining. Several instruments were deployed inside the SEAMIST{trademark}-lined boreholes to detect metals, radionuclides, moisture, and geologic variations. The liner protected the instruments from contamination, maintained support of the uncased borehole wall, and sealed the total borehole from air circulation. Recent activities included the installation of three multipoint vapor sampling systems and sensor integration systems in 100-foot-deep vertical boreholes. A long term pressure monitoring program has recorded barometric pressure effects at depth with relatively high spatial resolution. The SEAMIST{trademark} system has been integrated with a variety of hydrologic and chemical sensors for in-situ measurements, demonstrating its versatility as an instrument deployment system that allows easy emplacement and removal. Standard SEAMIST{trademark} vapor sampling systems were also integrated with state-of-the-art volatile organic compound analysis technologies. The results and status of these demonstration tests are presented.

  12. I Phone, You Phone, We All Phone with iPhone: Trademark Law and Ethics from an International and Domestic Perspective

    Science.gov (United States)

    Cowart, Tammy W.; Chumney, Wade M.

    2011-01-01

    In today's Internet-based and global business environment, the legal issues companies face will often involve issues of intellectual property. Virtually every product people purchase is protected by a trademark, a patent, and/or copyrights. Thus, basic concepts of intellectual property are a natural component in any business law or legal…

  13. NuFab trademark anti-contamination suit - OST reference No. 1855. Deactivation and decommissioning focus area

    International Nuclear Information System (INIS)

    1998-02-01

    Radiation workers at all US Department of Energy (DOE) sites require some form of protective clothing when performing radiological work. A large number of contaminated facilities at DOE site are currently or will eventually undergo some form of decontamination and decommissioning (D ampersand D), requiring some type of protective clothing, often in multiple layers. Protective clothing that does not allow perspiration to escape causes heat stress, which lowers worker comfort and productivity. This report describes the NuFab trademark anti-contamination. The suit is a one-piece, disposable, breathable, waterproof coverall with a single front zipper. Constructed of tri-laminated composite material using spun-bonded polypropylene and microporous film layers, the suit is certified as incineratorable

  14. Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment.

    Science.gov (United States)

    Terpos, E; Migkou, M; Christoulas, D; Gavriatopoulou, M; Eleutherakis-Papaiakovou, E; Kanellias, N; Iakovaki, M; Panagiotidis, I; Ziogas, D C; Fotiou, D; Kastritis, E; Dimopoulos, M A

    2016-05-27

    Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.

  15. Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance to lenalidomide and bortezomib in a multiple myeloma patient.

    Science.gov (United States)

    Yuan, Ji; Shah, Radhika; Kulharya, Anita; Ustun, Celalettin

    2010-07-01

    Aneuploidy is a very common prognostic factor in multiple myeloma (MM). Nonhyperdiploidy including near-tetraploidy (NT) is a poor prognostic indicator, compared to hyperdiploidy in multiple myeloma (MM). NT results from endoduplication of hypodiploidy. We report of a 55-year-old female patient diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The patient responded well to lenalidomide and dexamethasone for approximately 1 year. At the time of progression, she had become unresponsive to lenalidomide and subsequently bortezomib, and was found to have NT and loss of choromosome 13. There is another reported patient who had a possible interchange from nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled out. To our knowledge, this is the first patient in whom evolution of an abnormal clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the natural course of MM. This evolution is associated with resistance to novel drugs and poor prognosis in MM. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib

    Directory of Open Access Journals (Sweden)

    Barbara Muz

    2015-01-01

    Full Text Available Multiple myeloma (MM is a plasma cell malignancy localized in the bone marrow. Despite the introduction of novel therapies majority of MM patients relapse. We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1 play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy. However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics. Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy. We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress. At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival. This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.

  17. Gasification of residual waste by the PreCon {sup trademark} process on the basis of high-temperature Winkler gasification (HTW); Vergasung von Restmuell nach dem PreCon {sup trademark} -Verfahren auf Basis der Hochtemperatur-Winkler Vergasung (HTW)

    Energy Technology Data Exchange (ETDEWEB)

    Klein, J.; Luetge, C.; Deutsch, M. [Krupp Uhde GmbH, Dortmund (Germany); Wischnewski, R.; Mittelstaedt, A. [Rheinbraun AG, Koeln (Germany)

    1998-09-01

    The HTW process is an established technology. Experiments in the laboratory and in a demonstration plant resulted in a valid design basis for the PreCon {sup trademark} process. The economic efficiency and competitive strength of the process is outlined. (orig./SR) [Deutsch] Das HTW-Verfahren praesentiert sich als eine bewaehrte, grosstechnisch erprobte Technologie fuer eine geaenderte Applikation. Die Umsetzung der in den Versuchen im Technikum und an der Demonstrationsanlage gewonnenen positiven Ergebnisse fuehrt zu einer abgesicherten Auslegungsgrundlage fuer das PreCon {sup trademark} -Verfahren. Die Wirtschaftlichkeit und Wettbewerbsfaehigkeit des Verfahrens laesst sich schon heute darstellen. (orig./SR)

  18. Hospital de día: Actualización del protocolo de administración de Bortezomib subcutáneo y Plan de cuidados de enfermería

    OpenAIRE

    Álamo Perucha, Celia

    2014-01-01

    La actualización del protocolo para la administración de Bortezomib (Velcade®) es debida al cambio de vía de administración recientemente instaurado. Los protocolos en las unidades de enfermería proporcionan un consenso en el conjunto de actividades y procedimientos ante un determinado problema o actividad asistencial y que son realizados diariamente por este colectivo. Es necesaria la formalización en la ejecución y registro de cuidados de enfermería para poder realizar así una continuidad e...

  19. High strength structural applications for large diameter forgings of Beta-C trademark (Ti-3Al-8V-6Cr-4Mo-4Zr)

    International Nuclear Information System (INIS)

    Russo, P.A.; Wood, J.R.; Bhagat, R.B.

    1993-01-01

    A program was initiated by the Navy to explore the use of Beta-C trademark as a water brake cylinder for stopping the catapult on aircraft carriers. Two processing routes were explored to manufacture the water brake cylinder: (1) extrusion, and (2) trepanning of large billet and electron beam welding of an end cap. Mechanical property evaluation of material produced by both processes showed that each was capable of achieving the strength and toughness requirements. Economic considerations will dictate final process selection

  20. Analysis of access to patent information systems of Industrial Property Office CZ, European Patent Office, United States Patent and Trademark Office and World Intellectual Property Organization

    OpenAIRE

    Nowaková, Jana

    2015-01-01

    The master thesis analyses and compares selected accesses to patent information systems of Czech Industrial Property Office, European Patent Office, United States Patent and Trademark Office and World Intellectual Property Organization. This includes accesses via web sites of the institutions mentioned above and an access via Google Patents service. The thesis is divided into six parts. The first part discusses patent information systems, the second one gives an overview of the selected insti...

  1. Preliminary flowsheet: Ion exchange process for the separation of cesium from Hanford tank waste using Duolite{trademark} CS-100 resin

    Energy Technology Data Exchange (ETDEWEB)

    Eager, K.M.; Penwell, D.L.; Knutson, B.J.

    1994-12-01

    This preliminary flowsheet document describes an ion exchange process which uses Duolite{trademark} CS-100 resin to remove cesium from Hanford Tank waste. The flowsheet describes one possible equipment configuration, and contains mass balances based on that configuration with feeds of Neutralized Current Acid Waste, and Double Shell Slurry Feed. Process alternatives, unresolved issues, and development needs are discussed which relate to the process.

  2. What Intellectual Property Lawyers can learn from Barbra Streisand, Sepp Blatter, and the "Coca-Cola Cry-Baby": Dealing with "Trademark Bullying" in South Africa

    Directory of Open Access Journals (Sweden)

    André M Louw

    2013-12-01

    Full Text Available This article suggests some pause for reflection amongst intellectual property lawyers, and for serious consideration of the words of an internationally-renowned IP law expert: "Possessing a right does not mean that it is a good idea to enforce it always, and to the hilt. Discretion may be nine parts of possession". It provides some prominent, recent examples of trademark bullying or overly-aggressive enforcement in the IP law context. These examples are mainly from other jurisdictions but they are directly relevant to some of the IP law challenges present in South Africa at the moment. The article further examines why lawyers and rights' holders engage in trademark bullying (why it's done, and start to deal briefly with some of the legal implications. A future article is to examine the legal aspects of trademark bullying in much more detail and considers its legitimacy within the context of IP law, more generally, and some other areas of law, more specifically.

  3. DREAMS - a universal AMS facility based on the 6 MV-Tandetron trademark at FZD in Dresden

    Energy Technology Data Exchange (ETDEWEB)

    Akhmadaliev, Shavkat; Kolitsch, Andreas; Merchel, Silke; Moeller, Wolfhard [Forschungszentrum Dresden-Rossendorf e. V., Institute of Ion Beam Physics and Materials Research, Dresden (Germany)

    2010-07-01

    A new accelerator mass spectrometry (AMS) system has been installed at the Forschungszentrum Dresden-Rossendorf (FZD). The system is based on a 6 MV-Tandetron trademark accelerator produced by High Voltage Engineering Europe (HVEE). The AMS facility is specified for measurements of {sup 10}Be, {sup 14}C, {sup 26}Al, {sup 36}Cl, {sup 41}Ca and {sup 129}I with isotopic ratios of 10{sup -10} - 10{sup -16} and precision better than 0.3% for {sup 14}C/{sup 12}C. The system uses a bouncer sequential injector with two Cs-sputter ion sources and a 54 electrostatic analyser (ESA). On the high-energy site it has a 90 -analysing magnet, Faraday-Cups for stable nuclides, a 35 -ESA, a post-stripper foil, and a 30 -vertical magnet for suppression of interfering species, and gas ionisation chamber for detection of radionuclides. The Cockroft-Walton type high voltage generator provides a terminal voltage of up to 6 MV. The system is additionally equipped with a multipurpose ion injector containing a third Cs-sputter ion source and a duoplasmatron for high-energy ion implantation and ion-beam materials analysis.

  4. Development of a new neutron shielding material, TN trademark Resin Vyal for transport/storage casks for radioactive materials

    International Nuclear Information System (INIS)

    Abadie, P.

    2004-01-01

    TN trademark Resin Vyal, a patent pending composite, is a new neutron shielding material developed by COGEMA LOGISTICS for transport/storage casks of radioactive materials (spent fuel, reprocessed fuel,..). This material is composed of a thermosetting resin (vinylester resin in solution of styrene) and two mineral fillers (alumine hydrate and zinc borate). Its shielding ability for neutron radiation is related to a high hydrogen content (for slowing down neutrons) and a high boron content (for absorbing neutrons). Source of hydrogen is organic matrix (resin) and alumine hydrate; source of boron is zinc borate. Atomic concentrations are equal to 5.10 22 at/cm 3 for hydrogen and 9.10 20 at/cm 3 for boron. Due to the flame retardant character of components, the final material has a good fire resistance (it is auto-extinguishable). Its density is equal to 1,8. The manufacturing process of these material is easy: it consists in mixing the fillers and pouring in-situ (in cask); so, the curing of this composite, which leads to a three-dimensional structure, takes place at ambient temperature. Temperature resistance of this material was evaluated by performing exposition tests of samples at different temperatures (150 C to 170 C). According to tests results, its maximal temperature of use was confirmed equal to 160 C

  5. Advanced light water reactor plants System 80+{trademark} design certification program. Annual progress report, October 1, 1995--September 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The purpose of this report is to provide a status of the progress that was made towards Design Certification of System 80+{trademark} during the US government`s 1996 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2 and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems.

  6. Advanced light water reactor plants System 80+{trademark} design certification program. Annual progress report, October 1, 1994--September 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The purpose of this report is to provide the status of the progress that was made towards Design Certification of System 80+{trademark} during the US government`s 1995 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2, and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems.

  7. Advanced light water reactor plants System 80+trademark design certification program. Annual progress report, October 1, 1994 - September 30, 1995

    International Nuclear Information System (INIS)

    1998-01-01

    The purpose of this report is to provide the status of the progress that was made towards Design Certification of System 80+trademark during the US government's 1995 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2, and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems

  8. Advanced light water reactor plants System 80+trademark design certification program. Annual progress report, October 1, 1995 - September 30, 1996

    International Nuclear Information System (INIS)

    1996-01-01

    The purpose of this report is to provide a status of the progress that was made towards Design Certification of System 80+trademark during the US government's 1996 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2 and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems

  9. Simulink(Trademark) Controller for a Reluctance Motor With a Four-Pole Rotor and 36-Tooth Stator

    Science.gov (United States)

    Morrison, Carlos R.; Provenza, Andrew J.

    2017-01-01

    NASA Glenn Research Center has developed a Simulink(Trademark) controller logic for driving a room temperature, 36-teeth stator, four-pole rotor reluctance motor. The Simulink logic was extracted from an existing C++ motor controller that was previously employed to achieve a rotor speed of 3000 rpm. The Simulink controller has additional logic refinements that were not available in past C++ controller, such as the per rev logic component and its frequency filter. The filter provides a more accurate reading of the rotor input signals. The controller is versatile, and with slight modifications, can be used to drive other reluctance motor types incorporating dissimilar stator rotor pole combinations. The original C++ controller was designed with the goal (after appropriate modification) of controlling a future superconducting motor. This superconducting motor will be employed as a test bed for developing other superconducting aviation propulsion motors envisioned for future turbo-electric aircrafts. The Simulink results presented in this paper were generated from simulated rotor inputs. However, in an actual application, these simulated inputs are to be replaced by actual proximity probe signals emanating from D-Space hardware inputs.

  10. Tensile and electrical properties of unirradiated and irradiated Hycon 3HP{trademark} CuNiBe

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Eatherly, W.S. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    The unirradiated tensile properties of two different heats of Hycon 3HP{trademark} CuNiBe (HT Temper) have been measured over the temperature range of 20-500{degrees}C for longitudinal and long transverse orientations. The room temperature electrical conductivity has also been measured for both heats. Both heats exhibited a very good combination of strength and conductivity at room temperature. The strength remained relatively high at all test temperatures, with a yield strength of 420-520 MPa at 500{degrees}C. However, low levels of ductility (<5% uniform elongation) were observed at test temperatures above 200-250{degrees}C, due to flow localization adjacent to grain boundaries. Fission neutron irradiation to a dose of {approximately}0.7 dpa at temperatures between 100 and 240{degrees}C produced a slight increase in strength and a significant decrease in ductility. The measured tensile elongation increased with increasing irradiation temperature, with a uniform elongation of {approximately}3.3% observed at 240{degrees}C. The electrical conductivity decreased slightly following irradiation, due to the presence of defect clusters and Ni, Zn, Co transmutation products. The data indicate that CuNiBe alloys have irradiated tensile and electrical properties comparable or superior to CuCrZr and oxide dispersion strengthened copper at temperatures <250{degrees}C, and may be suitable for certain fusion energy structural applications.

  11. Evaluation of Material Models within LS-DYNA(Registered TradeMark) for a Kevlar/Epoxy Composite Honeycomb

    Science.gov (United States)

    Polanco, Michael A.; Kellas, Sotiris; Jackson, Karen

    2009-01-01

    The performance of material models to simulate a novel composite honeycomb Deployable Energy Absorber (DEA) was evaluated using the nonlinear explicit dynamic finite element code LS-DYNA(Registered TradeMark). Prototypes of the DEA concept were manufactured using a Kevlar/Epoxy composite material in which the fibers are oriented at +/-45 degrees with respect to the loading axis. The development of the DEA has included laboratory tests at subcomponent and component levels such as three-point bend testing of single hexagonal cells, dynamic crush testing of single multi-cell components, and impact testing of a full-scale fuselage section fitted with a system of DEA components onto multi-terrain environments. Due to the thin nature of the cell walls, the DEA was modeled using shell elements. In an attempt to simulate the dynamic response of the DEA, it was first represented using *MAT_LAMINATED_COMPOSITE_FABRIC, or *MAT_58, in LS-DYNA. Values for each parameter within the material model were generated such that an in-plane isotropic configuration for the DEA material was assumed. Analytical predictions showed that the load-deflection behavior of a single-cell during three-point bending was within the range of test data, but predicted the DEA crush response to be very stiff. In addition, a *MAT_PIECEWISE_LINEAR_PLASTICITY, or *MAT_24, material model in LS-DYNA was developed, which represented the Kevlar/Epoxy composite as an isotropic elastic-plastic material with input from +/-45 degrees tensile coupon data. The predicted crush response matched that of the test and localized folding patterns of the DEA were captured under compression, but the model failed to predict the single-cell three-point bending response.

  12. Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Leonard, John P; Kolibaba, Kathryn S; Reeves, James A; Tulpule, Anil; Flinn, Ian W; Kolevska, Tatjana; Robles, Robert; Flowers, Christopher R; Collins, Robert; DiBella, Nicholas J; Papish, Steven W; Venugopal, Parameswaran; Horodner, Andrew; Tabatabai, Amir; Hajdenberg, Julio; Park, Jaehong; Neuwirth, Rachel; Mulligan, George; Suryanarayan, Kaveri; Esseltine, Dixie-Lee; de Vos, Sven

    2017-11-01

    Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m 2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

  13. Catalytic Two-Stage Liquefaction (CTSL{trademark}) process bench studies and PDU scale-up with sub-bituminous coal. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Comolli, A.G.; Johanson, E.S.; Karolkiewicz, W.F.; Lee, L.K.T.; Stalzer, R.H.; Smith, T.O.

    1993-03-01

    Reported are the details and results of Laboratory and Bench-Scale experiments using sub-bituminous coal conducted at Hydrocarbon Research, Inc., under DOE Contract No. DE-AC22-88PC88818 during the period October 1, 1988 to December 31, 1992. The work described is primarily concerned with testing of the baseline Catalytic Two-Stage Liquefaction (CTSL{trademark}) process with comparisons with other two stage process configurations, catalyst evaluations and unit operations such as solid separation, pretreatments, on-line hydrotreating, and an examination of new concepts. In the overall program, three coals were evaluated, bituminous Illinois No. 6, Burning Star and sub-bituminous Wyoming Black Thunder and New Mexico McKinley Mine seams. The results from a total of 16 bench-scale runs are reported and analyzed in detail. The runs (experiments) concern process variables, variable reactor volumes, catalysts (both supported, dispersed and rejuvenated), coal cleaned by agglomeration, hot slurry treatments, reactor sequence, on-line hydrotreating, dispersed catalyst with pretreatment reactors and CO{sub 2}/coal effects. The tests involving the Wyoming and New Mexico Coals are reported herein, and the tests involving the Illinois coal are described in Topical Report No. 2. On a laboratory scale, microautoclave tests evaluating coal, start-up oils, catalysts, thermal treatment, CO{sub 2} addition and sulfur compound effects were conducted and reported in Topical Report No. 3. Other microautoclave tests are described in the Bench Run sections to which they refer such as: rejuvenated catalyst, coker liquids and cleaned coals. The microautoclave tests conducted for modelling the CTSL{trademark} process are described in the CTSL{trademark} Modelling section of Topical Report No. 3 under this contract.

  14. Plain packaging and indirect expropriation of trademark rights under BITs: does FCTC help to establish a right to regulate tobacco products?

    Science.gov (United States)

    Lo, Chang-Fa

    2012-12-01

    Recently the giant tobacco company Philip Morris served its notice to launch an investor-to-state dispute settlement proceeding against the Australian Government for its introduction of plain packaging requirements on tobacco products. It is an important event in the field of intellectual property, investment and international health law. The fundamental questions involved are whether the restriction of trademark rights as a result of the plain packaging requirement is a compensable indirect expropriation under BITs or whether it falls within the scope of government's right to regulate and thus become not compensable. This paper is of the view that the requirement of plain packaging will deprive the essential value or core function of trademark rights and thus constitutes an indirect expropriation under BITs. However, such indirect expropriation meets the public interest requirement and the necessity requirement. The paper further argues that sovereign States have an inherent right to regulate domestic economic activities. Since the pain packaging requirements provided in the FCTC Guidelines are expected to protect the value of human lives and health, the protected values clearly outweigh the affected commercial interests of tobacco companies. Also the justification for host States to adopt a plain packaging policy is strong. Thus, the interpreters of BITs need to pay higher respect to the host State's sovereign power concerning its right to regulate tobacco products for a legitimate purpose. The conclusion of the paper is that the host States should enjoy a defense of the right to regulate to refuse compensation. The author believes that this is the only reasonable conclusion to avoid possible conflicts between different treaty systems (BITs and the FCTC) and between different legal systems and fields (trademark law, investment law and international health law).

  15. Non-Academic Jobs for Fellows in Law Firms, Patent and Trademark Office and Scientific Intellectual Property | Center for Cancer Research

    Science.gov (United States)

    This workshop helps CCR fellows and staff scientists learn about and better position themselves for potential job opportunities at law firms, patent and trademark, and intellectual property protection across the biotechnology and pharmaceutical industries. Guest speakers will shed light on how to best position yourself for obtaining these types of positions and how to improve your chances of success. They will describe ways in which you can use your time at NIH to better prepare for opportunities that may arise down the road in these fields.

  16. Fermi UNIX trademark environment

    International Nuclear Information System (INIS)

    Nicholls, J.

    1991-03-01

    The introduction of UNIX at Fermilab involves multiple platforms and multiple vendors. Additionally, a single user may have to use more than one platform. This heterogeneity and multiplicity makes it necessary to define a Fermilab environment for UNIX so that as much as possible the systems ''look and feel'' the same. We describe our environment, including both the commercial products and the local tools used to support it. Other products designed for the UNIX environment are also described. 19 refs

  17. MCNP trademark directions

    International Nuclear Information System (INIS)

    Hendricks, J.S.

    1994-01-01

    The MCNP code development program is a relatively large and rapidly changing project in the small and highly-specialized field of radiation transport, specifically radiation protection and shielding. A number of major new MCNP initiatives are described in the subsequent papers in this session. The focus of this paper is the important new developments not described elsewhere and a number of recent developments that have been available since MCNP4A but have gone unnoticed. In particular, we report for the first time a new MCNP quality assurance initiative providing 97% test coverage, a new MCNP feature enabling plotting of nuclear data, and the other new features developed so far for MCNP4B. Finally, an attempt is made to articulate how all these fit together into the overall MCNP development program

  18. Advanced Ada (Trademark).

    Science.gov (United States)

    1984-07-01

    Hedge"), new String’("Seasonal Shrub"), new F’ring’("Jolly Gymnosperm "), new String’("Ceremonial Cedar"), new String’ ("Inebriate Evergreen")); So, we...8217("Christmas Tree"), new String’("Holiday Hedge"), new String’ ("Seasonal Shrub"), new String’("Jolly Gymnosperm "), new Strina’("Ceremonial Cedar

  19. Fermi UNIX trademark environment

    Energy Technology Data Exchange (ETDEWEB)

    Nicholls, J.

    1991-03-01

    The introduction of UNIX at Fermilab involves multiple platforms and multiple vendors. Additionally, a single user may have to use more than one platform. This heterogeneity and multiplicity makes it necessary to define a Fermilab environment for UNIX so that as much as possible the systems look and feel'' the same. We describe our environment, including both the commercial products and the local tools used to support it. Other products designed for the UNIX environment are also described. 19 refs.

  20. TN trademark FLEX: a new generation of fluorocarbon o-rings developed by COGEMA logistics with enhanced characteristics at low temperature (-40 C)

    International Nuclear Information System (INIS)

    Issard, H.; Andre, R.

    2004-01-01

    Three main types of elastomers are used for the sealing of radioactive material transport casks with elastomeric gaskets: EPDM, fluorocarbons type Viton registered (standard designation: FKM) and silicon rubbers. Each rubber has specific characteristics in terms of temperature range, permeability, coefficient of expansion.. For the casks where high temperatures can be reached (200 C in continuous using), FKM gaskets are generally used. The problem is that this type of gasket does not guarantee the leaktightness at -40 C, which is a regulatory requirement. Two solutions are generally used: to specify a minimum heat load or a minimum ambient temperature. The direct consequence is that it is impossible to get B(U) approvals on the new concepts when FKM gaskets are used but only B(M) approvals, which generate significant additional justification costs (multiple submittals of Safety Analysis Reports, calculation of the minimum heat load or of the minimum ambient temperature..). Thus, it is important to develop gaskets with the same performance as FKM gaskets at high temperature but with enhanced performance at low temperature (and mainly, which guarantee the leaktightness at -40 C). COGEMA LOGISTICS has qualified a new generation of fluorocarbon O-rings (TN trademark FLEX gaskets) which can be used in continuous service on a -47 C/+200 C temperature range. TN trademark FLEX gaskets will be implemented on new casks designs

  1. Use of LS-DYNA(Registered TradeMark) to Assess the Energy Absorption Performance of a Shell-Based Kevlar(TradeMark)/Epoxy Composite Honeycomb

    Science.gov (United States)

    Polanco, Michael

    2010-01-01

    The forward and vertical impact stability of a composite honeycomb Deployable Energy Absorber (DEA) was evaluated during a full-scale crash test of an MD-500 helicopter at NASA Langley?s Landing and Impact Research Facility. The lower skin of the helicopter was retrofitted with DEA components to protect the airframe subfloor upon impact and to mitigate loads transmitted to Anthropomorphic Test Device (ATD) occupants. To facilitate the design of the DEA for this test, an analytical study was conducted using LS-DYNA(Registered TradeMark) to evaluate the performance of a shell-based DEA incorporating different angular cell orientations as well as simultaneous vertical and forward impact conditions. By conducting this study, guidance was provided in obtaining an optimum design for the DEA that would dissipate the kinetic energy of the airframe while maintaining forward and vertical impact stability.

  2. El TLT (Trademark Law Treaty y los retos para la superintendencia de industria y comercio como oficina nacional de propiedad industrial

    Directory of Open Access Journals (Sweden)

    María Carolina Corcione Morales

    2010-11-01

    Full Text Available La Superintendencia de Industria y Comercio, como Oficina Nacional de Propiedad Industrial, se enfrentará a un nuevo sistema de registro de marcas una vez sea incorporado a nuestro ordenamiento el Tratado sobre Derecho de Marcas – TLT (Trademark Law Treaty. Los retos procesales que se avecinan al introducirse el registro multiclase en el actual sistema colombiano, ameritan un análisis detenido del contenido del tratado y de las medidas que el gobierno colombiano deberá adoptar para garantizar una implementación exitosa del instrumento internacional. La entrada en vigencia del TLT, si bien no implica un reto que obligue replantear las fuentes y principios del derecho de la propiedad industrial, es un desafío de índole procesal que hace necesario adecuar el actual funcionamiento de la Superintendencia de Industria y Comercio, a nivel humano y tecnológico.

  3. BetaScint{trademark} fiber-optic sensor for detecting strontium-90 and uranium-238 in soil. Innovative technology summary report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Accurate measurements of radioactivity in soils contaminated with Strontium-90 (Sr-90) or Uranium-238 (U-238) are essential for many DOE site remediation programs. These crucial measurements determine if excavation and soil removal is necessary, where remediation efforts should be focused, and/or if a site has reached closure. Measuring soil contamination by standard EPA laboratory methods typically takes a week (accelerated analytical test turnaround) or a month (standard analytical test turnaround). The time delay extends to operations involving heavy excavation equipment and associated personnel which are the main costs of remediation. This report describes an application of the BetaScint{trademark} fiber-optic sensor that measures Sr-90 or U-238 contamination in soil samples on site in about 20 minutes, at a much lower cost than time-consuming laboratory methods, to greatly facilitate remediation. This report describes the technology, its performance, its uses, cost, regulatory and policy issues, and lessons learned.

  4. El TLT (Trademark Law Treaty y los retos para la Superintendencia de Industria y Comercio como Oficina Nacional de Propiedad Industrial

    Directory of Open Access Journals (Sweden)

    María Carolina Corcione Morales

    2010-11-01

    Full Text Available La Superintendencia de Industria y Comercio, como Oficina Nacional de Propiedad Industrial, se enfrentará a un nuevo sistema de registro de marcas una vez sea incorporado a nuestro ordenamiento el Tratado sobre Derecho de Marcas (Trademark Law Treaty –tlt–. Los retos procesales que se avecinan al introducirse el registro multiclase en el actual sistema colombiano ameritan un análisis detenido del contenido del tratado y de las medidas que el gobierno colombiano deberá adoptar para garantizar una implementación exitosa del instrumento internacional. La entrada en vigencia del tlt, si bien no implica un reto que obligue a replantear las fuentes y principios del derecho de la propiedad industrial, es un desafío de índole procesal que hace necesario adecuar el actual funcionamiento de la Superintendencia de Industria y Comercio a los aspectos humano y tecnológico.

  5. Passamaquoddy Technology Recovery Scrubber{trademark} at the Dragon Products, Inc. Cement Plant located in Thomaston, Maine. 1990 Annual technical report

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-31

    The background and process of the Passamaquoddy Technology Recovery Scrubber{trademark} are described. The Scrubber was developed for Dragon Cement Plant in Thomaston, Maine and facilitates a number of process improvements. The exhaust gas is scrubbed of SO{sub 2} with better than 90% efficiency. The kiln dust is cleaned of alkalines and so can be returned to kiln feed instead of dumped to landfill. Potassium sulfate in commercial quantity and purity can be recovered. Distilled water is recovered which also has commercial potential. Thus, various benefits are accrued and no waste streams remain for disposal. The process is applicable to both wet and dry process cement kilns and appears to have potential in any industry which generates acidic gaseous exhausts and/or basic solid or liquid wastes.

  6. Comparison of MCNP trademark and MAVRIC for the case of a radiography experiment with thick-walled multi-layered shielding and Co-60 source; Vergleich von MCNP trademark und MAVRIC am Beispiel eines Durchstrahlungsexperiments mit dickwandiger mehrschichtiger Abschirmung und Co-60 Quelle

    Energy Technology Data Exchange (ETDEWEB)

    Schloemer, L.; Phlippen, P.W. [WTI Wissenschaftlich-Technische Ingenieurberatung GmbH, Juelich (Germany)

    2012-11-01

    The application of calculation methods to demonstrate an effective radiation shielding requires validation with appropriate measurements. Experimental data on the shielding of high-energy gamma radiation representing the situation of a thick-wall container with lead insert and significant self-shielding of the inventory is not publicly available. Therefore the shielding efficiency of multi-layered shielding (Pb, polyethylene) of a container was measured using an industrial Co-60 point source and a precisely calibrated measuring system for different shielding situations and measuring positions outside of the shielding. The calculations were performed using the codes MCNP trademark and MAVRIC. The deviations of calculated and experimental data are constant within the uncertainty of the experimental set-up, no distance dependent drift was identified.

  7. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  8. PVMaT improvements in the manufacturing of the PVI Powergrid{trademark}: Final technical report, 27 October 1997--31 October 1998

    Energy Technology Data Exchange (ETDEWEB)

    Kaminar, N.R.; Alexander, T.; Amaya, J.; Bottenberg, W.R.; Carrie, P.; Chen, K.; Hobden, P.; Lawyer, G.; Zimmermann, J.; Sherring, C.

    1999-10-20

    Photovoltaics International, LLC (PVI), is improving the manufacturing of the Powergrid{trademark} under the Photovoltaic Manufacturing Technology (PVMaT) program in five basic areas: development of an advanced, state-of-the-art lens extrusion system; development of an advanced, state-of-the-art module side extrusion system; development of a second generation automated receiver assembly station; development of low-cost roll-formed steel panel frame members; and development of an automated module assembly process with low usage of volatile organic compounds and hazardous materials. The results of the program were as follows: (1) Manufacturing improvements have led to dramatic improvements in performance, quality, durability and cost. (2) The first ever ethylene vinyl acetate encapsulation system for photovoltaic concentrators was developed, thereby eliminating volatile organic compounds and hazardous materials in the encapsulation process. (3) An in-house extrusion system was developed that produces the highest quality cell assemblies at low labor cost. (4) An advanced automated cell assembly station was developed that produces quality cell assemblies at low labor cost. (5) Solvents have been eliminated in the module assembly eliminating volatile organic compounds and hazardous materials. (6) Roll formed steel panel frame members have been introduced to production that have dramatically reduced cost. (7) A snap-together module assembly has been developed that provides low-cost field assembly of components and thereby also greatly reduced shipping cost. The Powergrid has the potential to be very low cost in the short term. The PVI PVMaT program should allow PVI to reach the cost goals set by the company. This, in turn, will allow PVI to become a substantial player in the PV market and will allow the DOE goals of increased application of PV to become a reality.

  9. An Evaluation of the NIDS (registered trademark) ACE (trademark) Test

    Science.gov (United States)

    2014-06-30

    sulfate) 0.14 71.9 Cyanide (sodium) 2 14 Fluoroacetate (sodium) 0.0009 5.1 Mercury (chloride) 0.001 24.7 Nicotine 0.13 16.8 Paraquat ...ND Oxamyl 0.63 Yes (15 of 16) Yes (n= 3) Yes, 0.04 (n= 3) --- Paraquat (dichloride) 4.6 ND ND ND ND Pentachlorophenate (sodium) 71.9 ND ND Yes, 50...methylisoborneol (MIB)) and plant decomposition (humic and fulvic acids) found in certain source waters. Hard water (water high in calcium and magnesium

  10. CAMAC Driver Support for Windows NT trademark and Lunux trademark

    International Nuclear Information System (INIS)

    Slimmer, D.A.; Streets, J.M.

    1999-01-01

    CAMAC is a Modular Instrumentation and Digital Interface System defined as a standardized instrumentation system for Computer Automated Measurement and Control. CAMAC hardware and software has been defined by the NIM Committee (National Instrumentation Methods Committee) of the US Department of Energy and the ESONE Committee (European Standards on Nuclear Electronics Committee) of European Laboratories. Fermi National Accelerator Laboratory has for many years produced software packages that follow the ANSI/IEEE standard 758-1979 for a variety of computers, CAMAC controller interfaces, and operating systems. In order to enable the re-use of existing hardware and software, Fermilab now supports standard routine libraries and drivers for Windows NT 4.0 and the Linux operating systems for the Jorway 411s SCSI Bus CAMAC Driver[l] and the Jorway73A SCSI Bus CAMAC Crate Controller. A number of test stands and small experiments both on-site and off-site are using this software for their CAMAC data acquisition needs

  11. MCNP(trademark) Version 5

    International Nuclear Information System (INIS)

    Cox, Lawrence J.; Barrett, Richard F.; Booth, Thomas Edward; Briesmeister, Judith F.; Brown, Forrest B.; Bull, Jeffrey S.; Giesler, Gregg Carl; Goorley, John T.; Mosteller, Russell D.; Forster, R. Arthur; Post, Susan E.; Prael, Richard E.; Selcow, Elizabeth Carol; Sood, Avneet

    2002-01-01

    The Monte Carlo transport workhorse, MCNP, is undergoing a massive renovation at Los Alamos National Laboratory (LANL) in support of the Eolus Project of the Advanced Simulation and Computing (ASCI) Program. MCNP Version 5 (V5) (expected to be released to RSICC in Spring, 2002) will consist of a major restructuring from FORTRAN-77 (with extensions) to ANSI-standard FORTRAN-90 with support for all of the features available in the present release (MCNP-4C2/4C3). To most users, the look-and-feel of MCNP will not change much except for the improvements (improved graphics, easier installation, better online documentation). For example, even with the major format change, full support for incremental patching will still be provided. In addition to the language and style updates, MCNP V5 will have various new user features. These include improved photon physics, neutral particle radiography, enhancements and additions to variance reduction methods, new source options, and improved parallelism support (PVM, MPI, OpenMP).

  12. Recent developments in MCNPX trademark

    International Nuclear Information System (INIS)

    Hughes, H.G.; Adams, K.J.; Chadwick, M.B.

    1998-01-01

    The MCNPX Monte Carlo particle transport code is rapidly developing into a significant computational tool for high-energy transport applications. In this paper, the authors will discuss three recent enhancements to MCNPX: a new charged-particle collisional energy-loss model, a geometry-independent mesh-based tally system, and a radiography simulation capability

  13. Origen y evolución de las patentes y marcas en biomecánica deportiva. (Origin and evolution of patents and trademarks in sports biomechanics.

    Directory of Open Access Journals (Sweden)

    José L. González-Montesinos

    2012-10-01

    and analysis of data related to the movement and its causes. The Spanish Patent and Trademark Office (O.E.P.M. is the agency responsible for registering and patenting inventions in Spain. This patent submitted must meet requirements and pass a technical examination. Today we can find various patents for kinematic and kinetic analysis of the movement, formed by laser transmitters and receivers, high speed cameras or pressure sensors. Most research related to sports biomechanics using these devices for more accurate data, improve the quality of the research and therefore the physical performance. The purpose of this review article is to show the evolution of biomechanics in general and sports in particular, a number of patents registered in the O.E.P.M. and an explanation of how and where to register inventions. We have used the digital platform Esp@cenet, Invesnes for the revision of spanish patents origin and Google Patent for patents registered offices outside Spain.

  14. Development of a Quantitative TaqMan(trademark)-PCR Assay and Feasibility of Atmosphoric Collection for Coccidioides Immits for Ecological Studies

    International Nuclear Information System (INIS)

    Daniels, J.I.; Wilson, W.J.; DeSantis, T.Z.; Gouveia, F.J.; Anderson, G.L.; Shinn, J.H.; Pletcher, R.; Johnson, S.M.; Pappagianis, D.

    2002-01-01

    identified as a select (biological) agent in the federal Anti-Terrorist and Effective Death Penalty Act. Successful demonstration of these tools in this study will place this multidisciplinary team in a credible position to proceed with additional research designed to determine the climatic signals and ecological triggers that would be associated with the presence of this microorganism environmentally and that would correlate with subsequent outbreaks of Valley Fever clinically. Results from such future research would then provide the information needed for environmental intervention of the disease occurrence, well before clinical cases appear. The technology and modeling developed for such a study also could be used for determining the ecology of other environmentally linked, medically important infectious diseases that occur naturally or that might be introduced deliberately into environmental media indoors or outside. The following approach was taken to achieve the technological objectives of this study. First, the protocols for the TaqMan(trademark)-PCR assay were enhanced to achieve the superior specificity and sensitivity required for quantifying, from a DNA signature, those C. immitis spores that are present in calibration samples (consisting of known quantities of pure culture inoculated onto air-filter concentrate, and then removed, and the DNA extracted) and those that are present within the calibration range on air filters obtained from the field and handled similarly. Second, the feasibility of using advanced nuclepore air-filter media to collect the spores from ambient air in C immitis endemic areas in the Central Valley of California was evaluated. These membranes permit the physics of high-volume air sampling to be used to filter larger amounts of air than previously possible for detecting airborne microorganisms. Thus, the higher volume of air flow improves the likelihood of capturing on the filter any C. immitis spores resuspended from nearby soil, where

  15. The internet has to become more important for the trademark communication of energy supply companies; Die Bedeutung des Internet fuer die Markenkommunikation der EVU. Potenzial wird nur unzureichend genutzt

    Energy Technology Data Exchange (ETDEWEB)

    Grassmann, B. [Marketing und Vertrieb, T-Online International AG, Darmstadt (Germany)

    2003-03-24

    As a precondition for future multi utility offers, energy supply companies are nowadays focusing on customer orientation and the extension of trademarks. Within the next three years, the acquisition of new clients (who intend to change the energy supplier) will be the central issue. Thus, there are great challenges ahead. The internet offers an unrecognized potential for communication so far, but only 0.3 per cent of the overall advertising expenses are invested in online communication. (orig.) [German] Die Energieversorgungsunternehmen konzentrieren sich heute auf Kundenorientierung und Markenausbau als Voraussetzung fuer kuenftige Multi-Utility-Angebote. In drei Jahren wird die Akquisition neuer Wechselkunden das zentrale Thema sein. Die Herausforderungen sind also gross. Das Internet bietet bislang verkannte Kommunikationspotenziale, aber nur 0,3% der Gesamtwerbeausgaben werden in Online-Kommunikation investiert. (orig.)

  16. Development of the integrated, in-situ remediation technology. Topical report for tasks No. 8 and No. 10 entitled: Laboratory and pilot scale experiments of Lasagna{trademark} process, September 26, 1994--May 25, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Sa V.; Athmer, C.J.; Sheridan, P.W. [and others

    1997-04-01

    Contamination in low permeability soils poses a significant technical challenge to in-situ remediation efforts. Poor accessibility to the contaminants and difficulty in delivery of treatment reagents have rendered existing in-situ treatments such as bioremediation, vapor extraction, pump and treat rather ineffective when applied to low permeability soils present at many contaminated sites. This technology is an integrated in-situ treatment in which established geotechnical methods are used to install degradation zones directly in the contaminated W and electro-osmosis is utilized to move the contaminants back and forth through those zones until the treatment is completed. This topical report summarizes the results of the lab and pilot sized Lasagna{trademark} experiments conducted at Monsanto. Experiments were conducted with kaofinite and an actual Paducah soil in units ranging from bench-scale containing kg-quantity of soil to pilot-scale containing about half a ton of soil having various treatment zone configurations. The obtained data support the feasibility of scaling up this technology with respect to electrokinetic parameters as well as removal of organic contaminants. A mathematical model was developed that was successful in predicting the temperature rises in the soil. The information and experience gained from these experiments along with the modeling effort enabled us to successfully design and operate a larger field experiment at a DOE TCE-contaminated clay site.

  17. Impressions and purchasing intentions of Japanese consumers regarding pork produced by 'Ecofeed,' a trademark of food-waste or food co-product animal feed certified by the Japanese government.

    Science.gov (United States)

    Sasaki, Keisuke; Aizaki, Hideo; Motoyama, Michiyo; Ohmori, Hideyuki; Kawashima, Tomoyuki

    2011-02-01

    Impressions and purchasing intentions of Japanese consumers regarding pork produced by 'Ecofeed', a trademark of food-waste or co-product animal feeds certified by the Japanese government, were investigated by a questionnaire on the Internet. 'Ecofeed' did not elicit specific impressions as compared to domestic, imported, Kurobuta (in Japan), and specific pathogen-free (SPF) pork. Purchasing intent for 'Ecofeed' pork was the second lowest of the five pork products. Knowledge and purchasing experience regarding 'Ecofeed' pork was the lowest of the five pork products. Respondents were classified into four categories according to their impressions of 'Ecofeed' pork. The largest category of respondents did not have any specific impression of 'Ecofeed' pork and had little knowledge of pork farming. A category that had a positive impression for 'Ecofeed' pork had high knowledge of the pork farming system. In order to establish 'Ecofeed' pork in Japan, our results suggest that information disclosure and education about 'Ecofeed', its certification system, environmental benefits and the current self-efficiency ratio of animal feed, are needed. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Animal Science.

  18. An investigation of the applicability of the new Reillex trademark-HPQ anion exchange resin system for technetium/rhenium and uranium in the Hanford waste tanks. Milestone 4 final report

    International Nuclear Information System (INIS)

    Ashley, K.R.; Ball, J.R.; Cobb, S.L.; Adams, J.M.; Young, D.A.

    1994-01-01

    Results of the measurements of the exchange capacity and K d values for ReO 4 - on Reillex trademark-HPQ as a function of nitric acid and hydroxide concentration, temperature, and ten months time will be reported. Results of the breakthrough volumes for UO 2 2+ on Reillex-HPQ chromatography columns as a function of carbonate ion concentration in high nitrate ion concentrations and various column sizes will be reported. Individual sections of this report describe the following: the sorption behavior of ReO 4 - on the Reillex-HPQ between pH 2 and 12 in 1.00 M NaNO 3 ; results of the measurements of the K d values for ReO 4 - on Reillex-HPQ and on Reillex-HP as a function of nitrate and hydroxide ion concentrations; the sorption behavior of ReO 4 - on Reillex-HPQ resin in base with time as a variable; the results of the early attempts at determining the K d values for Na 4 UO 2 (CO 3 ) 3 on Reillex-HPQ resin; and the breakthrough of UO 2 (NO 3 ) 2 in varying nitric acid solutions on Reillex-HPQ columns

  19. Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats Estudo da bioequivalência de quatro diferentes marcas comerciais de maleato de enalapril em ratos espontaneamente hipertensos

    Directory of Open Access Journals (Sweden)

    Nilo César do Vale Baracho

    2008-04-01

    Full Text Available INTRODUCTION: High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. PURPOSE: To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR. METHODS: Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. RESULTS: The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. CONCLUSION: The use of generic drug and similars (A and B drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.INTRODUÇÃO: A hipertensão arterial é uma doença sistêmica que traz grandes repercussões clínicas e psico-sociais, cursa com uma elevada morbi-mortalidade e gera elevados gastos para o sistema de saúde. Seu tratamento envolve a utilização de fármacos anti-hipertensivos, os quais são comercializados como remédios de marca, genéricos ou similares. PURPOSE: Verificar o efeito anti-hipertensivo produzido por dose igualitária de diferentes marcas de maleato de enalapril, em ratos naturalmente hipertensos. MÉTODOS: Foram administrados, por meio de gavagem, 15 mg/kg de maleato de enalapril em 50 ratos naturalmente hipertensos e verificada a pressão arterial, através de pletismografia de cauda, a cada três dias, em um período de 16 dias. RESULTADOS

  20. Patents and Trademarks as Information Sources and the Turkish Patent Institute Bilgi Kaynağı Olarak Patentler, Markalar ve Türk Patent Enstitüsü

    Directory of Open Access Journals (Sweden)

    Erdoğan Karaahmet

    1995-12-01

    Full Text Available The protection of industrial property rights in a country is an important factor in encouraging the invention activities, application of new technologies to industry, increasing foreign investment and supporting national and international trade. The present industrial property system of Turkey, which is one of the first countries in the world that started the protection of industrial property rights, includes protection of patents and trademarks only. This paper discusses the importance of access to technological and commercial information, describes the basic concepts of industrial property rights, and introduces the Turkish Patent Institute, its structure and func-tions along with information and documentation services it offers. Bir ülkedeki sınai mülkiyet haklarının korunması, buluş faaliyetlerinin gelişmesi, sanayie yeni teknolojilerin uygulanması, yabancı yatırımların artması, ulusal ve uluslararası ticaretin desteklenmesi için çok önemli bir faktördür. Dünyadaki sınai mülkiyet haklarını koruyan ilk ülkelerden biri olan Türkiye'de bugünkü sınai mülkiyet sistemi sadece patent ve marka korunmasını içermektedir. Bu çalışmada teknolojik ve ticari bilgiye erişimin önemi tartışılmakta, sınai mülkiyet hakları ile ilgili temel kavramlar açıklanmakta, Türk Patent Enstitüsünün yapısı, işlevleri ve verdiği enformasyon ve dokümantasyon hizmetleri ve sahip olduğu olanaklar tanıtılmaktadır.

  1. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    Science.gov (United States)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  2. Risk Metrics for Android (trademark) Devices

    Science.gov (United States)

    2017-02-01

    Variance of data. Mobile Application Security Triage (MAST) uses MCA to rank Android™ apps in order of relative suspicion. MAST works as follows: 1...authentication numbers (mTANs) by directing users to download an app that promises safer online banking. Once downloaded, user mTANS and Short Message Service ...et al., propose Mobile Application Security Triage (MAST) [34] an optimization of Android™ app market malware evaluation processes utilizing

  3. Underwater inspection robot - AIRIS 21''trademark''

    International Nuclear Information System (INIS)

    Koji, K.

    1999-01-01

    Highly reliable, cost-effective and extended examination coverage are three big demands for newly developed ISI equipment. AIRIS 21 (advanced inspection system for reactor pressure vessel and internals) which is a state-of-the-art next generation device, has been developed to reply to these demands. The device can reduce the inspection cost and increase the reliability and inspection coverage. The AIRIS 21 swims in the water toward an area to be inspected and sticks to the vessel wall using two propellers. After it sticks on the wall, the spinning speed of propellers is controlled to keep the device on the wall with constant vacuum force. Then it travels on the wall freely by two driving wheels and one trip measuring wheel. This manner of new examination system is quite different from the other conventional BWR-ID systems. This new inspection system is dramatically reduced its size [W550 x L600 x H55 (mm)] and weight [13.6 (kg)] compared with conventional system, and also saves ISI from being a critical path work because it needs no special tools, such as a large crane for handling. With AIRIS 21, it is possible to perform ID inspection of RPV welds in parallel with fuel shuffling and other core activities. (orig.)

  4. THE INTENSIVE AND TECHNOLOGY AS A TRADEMARK

    Directory of Open Access Journals (Sweden)

    Thiago Quinellato Louro

    2012-06-01

    Full Text Available Objetivos: identificar a percepção dos profissionais de enfermagem acerca da assistência de enfermagem prestada no ambiente das UTIs; descrever o uso de tecnologias duras nas unidades de terapia intensiva do ponto de vista da equipe de enfermagem; e analisar as implicações deste uso na assistência aos clientes críticos em terapia intensiva. Métodos: estudo descritivo, exploratório, com abordagem quanti-qualitativa. O cenário foi composto por 02 UTIs, sendo uma em instituição Pública e outra privada, ambas situadas no município do Rio de Janeiro. Os sujeitos foram Enfermeiros e Técnicos de Enfermagem que desenvolviam atividades nas referidas instituições. A coleta dos dados ocorreu através de questionários com a utilização de roteiro estruturado contendo perguntas abertas. A análise dos dados quantitativos foi feita por meio de análise frequencial, para os dados qualitativos foi utilizada a análise temática. Resultados: em seus relatos, os sujeitos, nos revelaram sua preocupação a todo instante com os aspectos subjetivos que permeiam a assistência de enfermagem em UTI, embora o cuidado com as tecnologias tenha emergido nos discursos, os mesmos não foram supervalorizados. Conclusão: através dos depoimentos dos sujeitos conseguimos constatar como ocorre a utilização das máquinas e equipamentos e suas implicações no assistir de enfermagem nas UTIs, como instrumentos do cuidado, não como foco de atenção. Evidenciamos também que o uso das tecnologias duras na assistência de enfermagem em terapia intensiva trazem implicações sobretudo, no que se refere ao modo como os profissionais entendem estas unidades. Descritores: enfermagem; cuidados intensivos; tecnologia.

  5. EPRI's POWERCOACH trademark software development project

    International Nuclear Information System (INIS)

    Rost, S.; Leu, Kehshiou

    1993-01-01

    Today's complex bulk power market accounts for an estimated $35 billion in transactions a year, significantly more than a decade ago. With the increased levels of non-utility generation and changing strategies in the utility industry, it is anticipated that the trend toward rapid growth in the bulk power market will continue. This market has evolved from an ad hoc residual market to one that in some respects stands at par with the retail market in the plans of many utilities. The bulk power market is not based on the obligation to serve to the same extent as retail markets. Utility participation in this market is therefore purely voluntary. This freedom of action or inaction in the bulk power market actually renders corporate decision-making, investment related or operational, more complicated in many respects than in retail markets. Examples of the burgeoning uncertainties affecting the bulk power market include the rapid expansion of transactions undertaken through power pools, and the impact on utility planning and operations brought about by the abundance and price attractiveness of power available for flexible periods. These uncertainties present an ideal opportunity to employ state-of-the-art analytical models to facilitate the effective use of utility assets to foster the efficient functioning of the entire bulk power market. This paper will focus on the POWERCOACH methodology for short-term bulk power transaction analysis under conditions of uncertainty. In August 1992, UPMP began a seventeen month project to convert POWERCOACH from a methodology to a fully functional, commercial software package. UPMP is developing the POWERCOACH software with the extensive, direct involvement of thirty EPRI member utilities. A synopsis of POWERCOACH is presented

  6. MCNP trademark Software Quality Assurance plan

    International Nuclear Information System (INIS)

    Abhold, H.M.; Hendricks, J.S.

    1996-04-01

    MCNP is a computer code that models the interaction of radiation with matter. MCNP is developed and maintained by the Transport Methods Group (XTM) of the Los Alamos National Laboratory (LANL). This plan describes the Software Quality Assurance (SQA) program applied to the code. The SQA program is consistent with the requirements of IEEE-730.1 and the guiding principles of ISO 900

  7. Data analysis and visualization in MCNP trademark

    International Nuclear Information System (INIS)

    Waters, L.S.

    1994-01-01

    There are many situations where the user may wish to go beyond current MCNP capabilities. For example, data produced by the code may need formatting for input into an external graphics package. Limitations on disk space may hinder writing out large PTRAK files. Specialized data analysis routines may be needed to model complex experimental results. One may wish to produce particle histories in a format not currently available in the code. To address these and other similar concerns a new capability in MCNP is being tested. A number of real, integer, logical and character variables describing the current and past characteristics of a particle are made available online to the user in three subroutines. The type of data passed can be controlled by cards in the INP file. The subroutines otherwise are empty, and the user may code in any desired analysis. A new MCNP executable is produced by compiling these subroutines and linking to a library which contains the object files for the rest of the code

  8. 77 FR 47528 - International Trademark Classification Changes

    Science.gov (United States)

    2012-08-09

    ... and identified goals designed to promote innovation; (8) considered approaches that reduce burdens and... and substitutes for all these materials, or of plastics. 21. Household or kitchen utensils and... activities. 42. Scientific and technological services and research and design relating thereto; industrial...

  9. Criticality calculations with MCNP trademark: A primer

    International Nuclear Information System (INIS)

    Harmon, C.D. II; Busch, R.D.; Briesmeister, J.F.; Forster, R.A.

    1994-01-01

    With the closure of many experimental facilities, the nuclear criticality safety analyst increasingly is required to rely on computer calculations to identify safe limits for the handling and storage of fissile materials. However, in many cases, the analyst has little experience with the specific codes available at his/her facility. This primer will help you, the analyst, understand and use the MCNP Monte Carlo code for nuclear criticality safety analyses. It assumes that you have a college education in a technical field. There is no assumption of familiarity with Monte Carlo codes in general or with MCNP in particular. Appendix A gives an introduction to Monte Carlo techniques. The primer is designed to teach by example, with each example illustrating two or three features of MCNP that are useful in criticality analyses. Beginning with a Quickstart chapter, the primer gives an overview of the basic requirements for MCNP input and allows you to run a simple criticality problem with MCNP. This chapter is not designed to explain either the input or the MCNP options in detail; but rather it introduces basic concepts that are further explained in following chapters. Each chapter begins with a list of basic objectives that identify the goal of the chapter, and a list of the individual MCNP features that are covered in detail in the unique chapter example problems. It is expected that on completion of the primer you will be comfortable using MCNP in criticality calculations and will be capable of handling 80 to 90 percent of the situations that normally arise in a facility. The primer provides a set of basic input files that you can selectively modify to fit the particular problem at hand

  10. Industrial Partnership Prosperity Game{trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Boyak, K.; Berman, M.; Beck, D.

    1998-02-01

    Prosperity Games TM are an outgrowth and adaptation move/countermove and seminar War Games. Prosperity Games TM are simulations that explore complex issues in a variety of areas including economics, politics, sociology, environment, education, and research. These issues can be examined from a variety of perspectives ranging from a global, macroeconomic and geopolitical viewpoint down to the details of customer/supplier/market interactions in specific industries. All Prosperity Games TM are unique in that both the game format and the player contributions vary from game to game. This report documents the Industry Partnership Prosperity Game sponsored by the Technology Partnerships and Commercialization Center at Sandia National Laboratories. Players came from the Sandia line organizations, the Sandia business development and technology partnerships organizations, the US Department of Energy, academia, and industry The primary objectives of this game were to: explore ways to increase industry partnerships to meet long-term Sandia goals; improve Sandia business development and marketing strategies and tactics; improve the process by which Sandia develops long-term strategic alliances. The game actions and recommendations of these players provided valuable insights as to what Sandia can do to meet these objectives.

  11. O mundo de Ronald McDonald: sobre a marca publicitária e a socialidade midiática The world of Ronald McDonald: on the trademark and the mediatic sociality

    Directory of Open Access Journals (Sweden)

    Isleide Arruda Fontenelle

    2002-06-01

    Full Text Available O palhaço Ronald McDonald -- uma das imagens de marca da Corporação McDonald's -- é tomado como paradigma para pensarmos as relações entre mercado, mídia e entretenimento, as quais tem uma ligação direta com o que estamos conceituando como "socialidade midiática". Enquanto uma metáfora ideal de uma propaganda que parece não querer mais fazer sentido, a história do palhaço nos permite desvendar os sentidos contidos em duas das principais práticas do marketing moderno, a propaganda e a publicidade, revelando-nos como, entre o nonsense da propaganda contemporânea e uma publicidade que fundiu realidade e ilusão, há uma relação visceral entre mídia e publicidade, que estabelece uma nova forma de comunicação, na qual o sujeito torna-se apenas um meio para fins que ele sabe quais são, mas, paradoxalmente, age como se não soubesse. Tal paradoxo é revelador de uma forma de subjetividade profundamente marcada pela mídia enquanto agente socializador, na medida em que a atuação da mídia como mediador da socialidade contemporânea acabou por alterar o nosso universo perceptivo, saturando o nosso imaginário de uma forma radicalmente nova. Some-se a isso o fato de que a "socialidade midiática" implica uma nova forma de representação do sujeito no registro do "espetáculo", no sentido de que "estar na imagem é existir". Desnecessário dizer o quanto essas questões precisam ser contempladas pelos estudos contemporâneos sobre os processos de socialização e o quanto são desafiadoras para aqueles que atuam no universo da educação.The clown Ronald McDonald -- one of the trademarks of the McDonald's Corporation -- is taken as a paradigm to reflect upon the relations between market, media, and entertainment, which have a direct link with what we define as "mediatic sociality". As an ideal metaphor of an advertising that no longer seems to attempt to make sense, the story of the clown allows us to unveil the meanings contained

  12. TRIPs公約、NAFTA、我國「商標法」有關「仿品進口」邊境管制措施之比較研究 Border Measures Provisions of Counterfeiting: A Comparision Study of TRIPs, NAFTA and Taiwan Trademark Law

    Directory of Open Access Journals (Sweden)

    易建明 Jiann-Ming Yih

    2005-06-01

    Full Text Available 仿品進口「邊境管制措施」為 TRIPs 協定(Agreement on Trade — Related Aspects of Intellectual Property Rights 簡稱TRIPs)第4 篇(第51 條至第60 條)所規範之範圍,另明文規範相關民事救濟。而我國2003 年「商標法」配合TRIPs 之修改等,主管機關已於2004 年9 月15 日訂定「海關查扣侵害商標權物品實施辦法」。本文就TRIPs、NAFTA、我國商標法有關「仿品」邊境管制措施之比較(區分為權利人的申請和海關依職權主動調查兩類),以作為我國未來與美國洽簽自由貿易協定是否採NAFTA 模式之參考。 (1有關「權利人的申請」邊境管制措施,我國若與美國洽簽自由貿易協定,若採NAFTA 模式,在「海關暫緩放行」的申請等,因大致相同,故無須修改我國「商標法」;至於有關「表面證據」以及表面證據之要件,係英美法之概念,在TRIPs、NAFTA「邊境管制措施」相關規定均強調「表面證據」;而我國2003 年「商標法」第65 條第2 項前段規定:「申請,應以書面為之,並釋明侵害之事實。」 (2另有關「海關依職權主動採取邊境管制措施」部分,我國2003 年「商標法」並未參照TRIPs 第58 條制定相關規範。由於TRIPs 第58 條並非強制性規範,我國未違反TRIPs 之規範。但TRIPs 與NAFTA 均明文規定「海關依職權主動採取邊境管制措施」,我國未來若與美國洽簽FTA 時,若採NAFTA 模式時應修改商標法,參照TRIPs 協定第58 條與NAFTA 第1718 條第11 項,增訂相關條文。 This Article tries to compare the regulations of border measures among TRIPs Agreement, NAFTA and Taiwan Trademark Law. The TRIPs Agreement distinguishes between infringement, for which civil judicial procedures and remedies must be available, and counterfeiting and piracy. In the case of counterfeiting, additional procedures and remedies, including border

  13. Technology Transition -- Lessons Learned from Fido (registered trademark)/PackBot (registered trademark)

    National Research Council Canada - National Science Library

    Parmentola, John A; Szkrybalo, Irena D

    2007-01-01

    .... The company is building a dog-like robot with the capability to run fast, traverse rough terrain, jump over obstacles 40 inches tall or 2 meters wide, and operate for 2 hours without refueling...

  14. Pump selection and Synergic Retrofit trademark; Pumpenauswahl und Synergetic Retrofit trademark

    Energy Technology Data Exchange (ETDEWEB)

    Hirschberger, M.; Kuhlmann, J.; Hofaecker, G. [Ruhrpumpen GmbH, Witten (Germany)

    2000-12-01

    Selection of the right pump for a given application is the crucial factor that determines its efficient and reliable operation. Of the performance data, the NPSHa value is the most important. The suction specific speed (SSS) may be an important decision aid. The achievable pump efficiency depends on the specific pump speed n. The pump should also run near optimum for optimum energy use and minimum vibrations. This will increase reliability and prolong the pump life. [German] Die Auswahl der richtigen Pumpe fuer den jewelligen Anwendungsfall ist entscheidend fuer den effizienten und zuverlaessigen Einsatz. Die Festlegung der Betriebsdaten ist dabei der erste wichtige Schritt, wobei der vorhandene NPSHa-Wert der Anlage von entscheidender Bedeutung ist. Die suction specific speed SSS kann dabei eine wichtige Entscheidungshilfe sein. Der erreichbare Wirkungsgrad ist von der spezifischen Drehzahl nq der Pumpe abhaengig. Des Weiteren ist es wichtig, dass die Pumpe im Bereich des Optimums arbeiten sollte. Sie nutzt dann die eingesetzte Energie optimal aus. In diesem Arbeitsbereich sind die Schwingungswerte und damit die Belastung der Pumpe am geringsten. Zuverlaessigkeit und Lebensdauer werden somit erhoeht. (orig.)

  15. Microstructural Characterization of Foil-Gage Haynes (register trademark) 230 (registered trademark) (Preprint)

    Science.gov (United States)

    2010-01-01

    Haynes 230is a solid-solution- and carbide-strengthened nickel-based superalloy noted for its excellent high-temperature strength, resistance to... cobalt , iron and boron represent ‘not to exceed’ value and that the measured values from the ingot in this study meet this standard. Material...2002). Superalloys . A Technical Guide. 2nd edition. Materials Park: ASM International. 12 Davis, J.R., (1997). Heat Resistant Materials Materials

  16. Trademark protection for store designs. One trademark a day keeps apple’s competitors away

    Directory of Open Access Journals (Sweden)

    Thomas Farkas

    2014-11-01

    Full Text Available Companies spend a significant part of their investment in order to create a Brand experience for the consumer. Besides large sums spent on the design of consumer goods, companies such as Apple are eager to create a brand experience by implementing a certain store design. Hence, these companies have a well-reasoned urge to protect such distinct store designs utilizing the current intellectual property system. In the tradition of the U.S. approach, where the get-up of a business venue can be protected by trade dress law, the most recent European Jurisprudence seems to tend towards the protection of such a get-up by trade mark law. As this could be good news for companies with a distinct store concept and design, this new approach also raises some concern: How will the protection of the get-up of a business venue affect competition? What are the measures to guarantee only distinct and non-functional store designs will find their way into the holy land of trade mark protection? This article analyzes and compares the current legal situation in the U.S. and the EU and discusses the available measures in place that will safeguard an undistorted competition.

  17. Trademark protection for store designs. One trademark a day keeps apple’s competitors away

    Directory of Open Access Journals (Sweden)

    Thomas Farkas

    2014-12-01

    Full Text Available Companies spend a significant part of their investment in order to create a Brand experience for the consumer. Besides large sums spent on the design of consumer goods, companies such as Apple are eager to create a brand experience by implementing a certain store design. Hence, these companies have a well-reasoned urge to protect such distinct store designs utilizing the current intellectual property system. In the tradition of the U.S. approach, where the get-up of a business venue can be protected by trade dress law, the most recent European Jurisprudence seems to tend towards the protection of such a get-up by trade mark law. As this could be good news for companies with a distinct store concept and design, this new approach also raises some concern: How will the protection of the get-up of a business venue affect competition? What are the measures to guarantee only distinct and non-functional store designs will find their way into the holy land of trade mark protection? This article analyzes and compares the current legal situation in the U.S. and the EU and discusses the available measures in place that will safeguard an undistorted competition.

  18. Technology Transition -- Lessons Learned from Fido (registered trademark)/PackBot (registered trademark)

    Science.gov (United States)

    2007-12-01

    clear that much mutual benefit can be derived from more direct collabora- tions between ATEC and Army S&Es. But the idea of a robotic dog remotely sensing...Dynamics Inc. The company is building a dog -like robot with the capability to run fast, traverse rough terrain, jump over obstacles 40" tall or 2 meters...servists called in from the Arizona Na- tional Guard put a robotic dog through its paces during a rigorous test to see if it could find explosives in

  19. Interpreting Capability Maturity Model(Trademark) Integration (CMMI(Trademark)) for COTS-Based Systems

    National Research Council Canada - National Science Library

    Tyson, Barbara

    2003-01-01

    ...: adjusted roles and responsibilities, new skills, and different processes. Practitioners are often surprised to find that building and supporting COTS-based systems demands more, not less, discipline in their management and engineering practices...

  20. Potential organic herbicides for squash production: Pelargonic acid herbicides AXXE (registered trademark) and Scythe (registered trademark)

    Science.gov (United States)

    Organic squash (Cucurbita pepo L.) producers need appropriate herbicides that can effectively provide season- long weed control. Research was conducted in southeast Oklahoma (Atoka County, Lane, OK) to determine the impact of potential organic herbicides on weed control efficacy, crop injury, and y...

  1. Curcumin-bortezomib loaded polymeric nanoparticles for synergistic cancer therapy

    Czech Academy of Sciences Publication Activity Database

    Medel, S.; Syrová, Z.; Kováčik, L.; Hrdý, J.; Hornacek, M.; Jäger, Eliezer; Hrubý, Martin; Lund, R.; Cmarko, D.; Štěpánek, Petr; Raška, I.; Nyström, B.

    2017-01-01

    Roč. 93, August (2017), s. 116-131 ISSN 0014-3057 R&D Projects: GA MŠk(CZ) 7F14009 Institutional support: RVO:61389013 Keywords : polymeric nanoparticles * light scattering * flow cytometry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.531, year: 2016

  2. Comment: Convergence of Trademark Law and E-Commerce ...

    African Journals Online (AJOL)

    The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how to print, save, and work with PDFs, Highwire Press provides a helpful Frequently Asked Questions about PDFs.

  3. ASCR{trademark}: lower NOx removal costs without sacrificing performance

    Energy Technology Data Exchange (ETDEWEB)

    Bible, S.; Rummenhohl, V.; Siebeking, M.; Thomas, R.; Triece, C. [Fuel Tech (United States)

    2011-05-15

    With recent regulatory initiatives, the new Industrial Emissions Directive in Europe, and new rules being proposed by EPA in the USA, the question for power plants is now whether they will be required to reduce NOx emissions in the future to stay in operation, but when. What is needed is a low-capital-cost but high-performance NOx removal technology. 7 figs.

  4. High temperature Hexoloy{trademark} SX silicon carbide. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, G.V.; Lau, S.K.; Storm, R.S. [Carborundum Co., Niagara Falls, NY (United States)

    1994-09-01

    HEXOLOY{reg_sign} SX-SiC, fabricated with Y and Al containing compounds as sintering aids, has been shown to possess significantly improved strength and toughness over HEXOLOY{reg_sign}SA-SiC. This study was undertaken to establish and benchmark the complete mechanical property database of a first generation material, followed by a process optimization task to further improve the properties. Mechanical characterization on the first generation material indicated that silicon-rich pools, presumably formed as a reaction product during sintering, controlled the strength from room temperature to 1,232 C. At 1,370 C in air, the material was failing due to a glass-phase formation at the surface. This glass-phase formation was attributed to the reaction of yttrium aluminates, which exist as a second phase in the material, with the ambient. This process was determined to be a time-dependent one that leads to slow crack growth. Fatigue experiments clearly indicated that the slow crack growth driven by the reaction occurred only at temperatures >1,300 C, above the melting point of the glass phase. Process optimization tasks conducted included the selection of the best SiC powder source, studies on mixing/milling conditions for SiC powder with the sintering aids, and a designed experiment involving a range of sintering and post-treatment conditions. The optimization study conducted on the densification variables indicated that lower sintering temperatures and higher post-treatment pressures reduce the Si-rich pool formation, thereby improving the room-temperature strength. In addition, it was also determined that furnacing configuration and atmosphere were critical in controlling the Si-rich formation.

  5. ReOpt[trademark] V2.0 user guide

    Energy Technology Data Exchange (ETDEWEB)

    White, M K; Bryant, J L

    1992-10-01

    Cleaning up the large number of contaminated waste sites at Department of Energy (DOE) facilities in the US presents a large and complex problem. Each waste site poses a singular set of circumstances (different contaminants, environmental concerns, and regulations) that affect selection of an appropriate response. Pacific Northwest Laboratory (PNL) developed ReOpt to provide information about the remedial action technologies that are currently available. It is an easy-to-use personal computer program and database that contains data about these remedial technologies and auxiliary data about contaminants and regulations. ReOpt will enable engineers and planners involved in environmental restoration efforts to quickly identify potentially applicable environmental restoration technologies and access corresponding information required to select cleanup activities for DOE sites.

  6. Testing of DentStat (trademark) and Competing Dental Materials

    Science.gov (United States)

    2014-06-13

    comparisons, DS showed the highest values, and in flexural modulus, 13 it was the second stiffest among the tested dental restoratives and cements ...NAVAL MEDICAL RESEARCH UNIT SAN ANTONIO TESTING OF DENTST AT™ AND COMPETING DENTAL MATERIALS Y OON HWANG PHD, JONATHAN STAHL DDS PHD, WAYNE M. D...LtCOL Wen Lien of the US Air Force Dental Evaluation and Consultation Service for assistance with the strength testing. 1 Reviewed and Approved by

  7. Health Hazard Potential of HYPOL (Trademark) Polyurethane Prepolymers

    Science.gov (United States)

    1975-05-01

    prepolymer container af ter each test, however, the viscosity gradually increased, indicating crystallization by moisture absorption . Moisture absorption ...foams. Suggested end uses include: absorbentproducts:cleaningpads; fiters;carpet undeda) - ment- floorand wall coverings: nonwoven binders: disposable... sound deadening, plano Srowth media, artificial sponges, and various household items. The fire retardant properties of HYPOLfoams are vastly superior

  8. Ada (Trademark) Joint Program Office Objectives and Progress -- through 1983.

    Science.gov (United States)

    1984-09-01

    Ada Byron, the countess of Lovelace . On 12 December 1980, the Under Secretary of Defense for Research and Engineering established the Ada ...language for DOD was named Ada , in honor of Augusta Ada Byron, the Countess of Lovelace . On 12 December 1980, the Under Secretary of Defense for Research... Ada Europe, JUG Ada and Ada LETTERS . Ada LETTERS is published bimonthly by SIGAda, and contains articles written by the AJPO and other Ada

  9. 37 CFR 2.193 - Trademark correspondence and signature requirements.

    Science.gov (United States)

    2010-07-01

    ... who has an actual written or verbal power of attorney or an implied power of attorney from the owner... questions the authority of a person who signs a communication that merely transmits paper documents. (f... advocating) of any document by any person, whether a practitioner or non-practitioner, constitutes a...

  10. The Flight Control System of the Hovereye (Trademark) VTOL UAV

    National Research Council Canada - National Science Library

    Binetti, Paolo; Trouchet, Daniel; Pollini, Lorenzo; Innocenti, Mario; Hamel, Tarek; Le Bras, Florent

    2007-01-01

    ..... This system stabilizes the vehicle, provides operators with easy manual flight commands, and automatically performs mission segments such as automatic landing, in the face of strong gusting wind...

  11. CMMI (registered trademark) for Services, Version 1.2

    Science.gov (United States)

    2009-02-01

    ITIL )  ISO/IEC 20000: Information Technology—Service Management  Control Objects for Information and related Technology (CobiT)  Information...html. Office of Government Commerce 2007a Office of Government Commerce. ITIL : Continual Service Improvement. London, UK: Office of Government...Commerce, 2007. Office of Government Commerce 2007b Office of Government Commerce. ITIL : Service Design. London, UK: Office of Government

  12. Peculiarities of Compensation Calculation for Illegal Use of Trademarks

    Directory of Open Access Journals (Sweden)

    Permyakova N. А.

    2013-10-01

    Full Text Available The article deals with the issues of compensatory method application of violated rights protection. Here are revealed the problematic issues of law enforcement practice in bringing to civil liability; Art. 1515 Civil code of the Russian Federation.

  13. Geothermal depth power plant; Geothermie Tiefenkraftwerk trademark (GTKW)

    Energy Technology Data Exchange (ETDEWEB)

    Haemmerle, Hubert [Ehoch 10 Projektentwicklungs GmbH, Wien (Austria); Pilgerstorfer, Thomas; Schubert, Wulf [Technische Univ. Graz (Austria). Inst. fuer Felsmechanik und Tunnelbau; Radoncic, Nedim

    2012-11-01

    The authors of the contribution under consideration report on a new concept for the utilization of geothermal energy. This concept provides itself due to the size of the usable reservoir, its performance in the area of conventional caloric power plants and its pronounced availability as a base load substitution for nuclear power plants as well as conventional gas and coal-fired power plants. A basic feasibility study was concluded. In addition to basic research, a variety of development work is required.

  14. Application of Empore trademark disk technology to environmental radiochemical analysis

    International Nuclear Information System (INIS)

    Smith, L.L.; Orlandini, K.A.; Alvarado, J.S.; Hoffmann, K.M.; Seely, D.C.; Shannon, R.T.

    1995-01-01

    The costs associated with environmental restoration and waste management at both government and private facilities are burdensome, and continue to grow. The Department of Energy estimates that over one million samples, many containing radioactive components, will be analyzed per annum to support remediation programs at its 4000 sites. The development and implementation of new analytical technologies can significantly reduce the high costs associated with these programs. Disk solid-phase extraction technology has been proven to be highly effective for sample preparation in the analysis of organic compounds, waste waters, and other aqueous samples. Disk technology significantly improves sample throughput, while reducing secondary waste and costs. Moreover, many of the hazardous chemicals associated with traditional procedures are eliminated. This technology may be readily automated and lends itself to field applications. Through a Cooperative Research and Development Agreement, the 3M Company and Argonne National Laboratory are expanding this technology to address sample preparation and recovery of radionuclides from aqueous samples, i.e., surface, ground, and drinking waters. Disks have been developed which demonstrate high selectivity and great affinity for important radionuclides, including 99 Tc, 89/90 Sr, and 226/228 Ra

  15. Overlay performance with advanced ATHENA trademark alignment strategies

    CERN Document Server

    Huijbregtse, Jeroen; Jeunink, Andre; Megens, Henry; Navarro, Ramon; Simons, Geert; Swinnen, Bart; Tolsma, Hoite; Van Bilsen, Frank; Van Haren, Richard

    2003-01-01

    The introduction of the ATHENA**T**M alignment sensor has made advanced applications of the sensor data increasingly important to meet the tightening overlay specifications for future technology nodes. As part of the total overlay budget, the effects of different alignment strategies on overlay performance need to be investigated. Keeping in mind that such strategies are simple and easy to use, two developments are addressed: advanced alignment recipes and advanced mark designs. (Edited abstract) 8 Refs.

  16. Environmental information volume: Liquid Phase Methanol (LPMEOH trademark) project

    International Nuclear Information System (INIS)

    1996-05-01

    The purpose of this project is to demonstrate the commercial viability of the Liquid Phase Methanol Process using coal-derived synthesis gas, a mixture of hydrogen and carbon monoxide. This report describes the proposed actions, alternative to the proposed action, the existing environment at the coal gasification plant at Kingsport, Tennessee, environmental impacts, regulatory requirements, offsite fuel testing, and DME addition to methanol production. Appendices include the air permit application, solid waste permits, water permit, existing air permits, agency correspondence, and Eastman and Air Products literature

  17. Environmental information volume: Liquid Phase Methanol (LPMEOH{trademark}) project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-05-01

    The purpose of this project is to demonstrate the commercial viability of the Liquid Phase Methanol Process using coal-derived synthesis gas, a mixture of hydrogen and carbon monoxide. This report describes the proposed actions, alternative to the proposed action, the existing environment at the coal gasification plant at Kingsport, Tennessee, environmental impacts, regulatory requirements, offsite fuel testing, and DME addition to methanol production. Appendices include the air permit application, solid waste permits, water permit, existing air permits, agency correspondence, and Eastman and Air Products literature.

  18. Sequence trademarks in oncogene associated microRNAs

    Science.gov (United States)

    Sharma, Sumit; Biswas, Sumit

    2011-01-01

    The last decade was taken by storm when the existence of a class of small (˜22nt long) non ― coding RNA species, known as microRNAs (miRNAs) came into light. MicroRNAs are one of the most abundant groups of regulatory genes in multicellular organisms and play fundamental roles in many cellular processes. Among these, miRNAs have been shown to prevent cell division and drive terminal differentiation, thus playing a causal role in the generation or maintenance of cancerous tumours. The unique expression profiles of different miRNAs in various types and stages of cancer suggest their performance as novel biomarkers. This discussion focuses on miRNAs implicated in cancer-associated events and strives to re-establish their sequential features which may classify them to be oncogenic. PMID:21814397

  19. Criticality calculations with MCNP{trademark}: A primer

    Energy Technology Data Exchange (ETDEWEB)

    Harmon, C.D. II; Busch, R.D.; Briesmeister, J.F.; Forster, R.A. [New Mexico Univ., Albuquerque, NM (United States)

    1994-06-06

    With the closure of many experimental facilities, the nuclear criticality safety analyst increasingly is required to rely on computer calculations to identify safe limits for the handling and storage of fissile materials. However, in many cases, the analyst has little experience with the specific codes available at his/her facility. This primer will help you, the analyst, understand and use the MCNP Monte Carlo code for nuclear criticality safety analyses. It assumes that you have a college education in a technical field. There is no assumption of familiarity with Monte Carlo codes in general or with MCNP in particular. Appendix A gives an introduction to Monte Carlo techniques. The primer is designed to teach by example, with each example illustrating two or three features of MCNP that are useful in criticality analyses. Beginning with a Quickstart chapter, the primer gives an overview of the basic requirements for MCNP input and allows you to run a simple criticality problem with MCNP. This chapter is not designed to explain either the input or the MCNP options in detail; but rather it introduces basic concepts that are further explained in following chapters. Each chapter begins with a list of basic objectives that identify the goal of the chapter, and a list of the individual MCNP features that are covered in detail in the unique chapter example problems. It is expected that on completion of the primer you will be comfortable using MCNP in criticality calculations and will be capable of handling 80 to 90 percent of the situations that normally arise in a facility. The primer provides a set of basic input files that you can selectively modify to fit the particular problem at hand.

  20. System 80+trademark standard design: CESSAR design certification

    International Nuclear Information System (INIS)

    1990-01-01

    This report has been prepared in support of the industry effort to standardize nuclear plant designs. The documents in this series describe the Combustion Engineering, Inc. System 80+ TM Standard Design

  1. Facility Composer (Trademark) and PACES (Trademark) Integration: Development of an XML Interface Based on Industry Foundation Classes

    National Research Council Canada - National Science Library

    Nachtigall, Susan D; Brucker, Beth A

    2007-01-01

    The Architectural Engineering and Construction (AEC) industry has made substantial effort over the past several years to create a standard facility modeling format that better enables their different software applications to work together...

  2. Facility Composer (Trademark) and PACES (Trademark) Integration: Development of an XML Interface Based on Industry Foundation Classes

    Science.gov (United States)

    2007-11-01

    275 VA MAGNETIC RESONANCE IMAGING (MRI) 276 VA RADIOLOGY SERVICE 277 VA RADIATION THERAPY SERVICE 278 VA MEDICAL RESEARCH & DEVELOPMENT 279 VA...87 DENTISTRY 88E DENTAL CLINIC W/DENTAL TUNNEL 91A CIRCULATION - DENTAL CLINIC 91B CIRCULATION - HEALTH/DENTAL CLINIC 91F CIRCULATION - TROOP AID... MAGNETICS AREA PEX MILITARY MED/PHYSICAL EXAM PFB PFC BUILDING SUPPORT AREA PGS PFC GENERAL STORAGE PHA PHARMACY PHO PHOTO/AVTR AREA PHY PHYSICAL

  3. 商標侵權案件定暫時狀態處分審酌因素之釋明──以eBay案後美國法發展與我國判決實務為中心 The Preliminary Showing on the Factors of Preliminary Injunction in Trademark Infringement Cases─Focusing on American Law after the eBay Case and Taiwan Court Decisions

    Directory of Open Access Journals (Sweden)

    范智達 Jr-Da Fan

    2015-12-01

    要求原告花費額外資源去釋明本案勝訴可能性以外之其他因素事實。 In eBay v. MercExchange (2006, the U.S. Supreme Court held that courts must apply the traditional four-factor test for injunctive relief in every case. These “principles of equity” required courts to employ the traditional four-factor test under which the plaintiff must demonstrate (1 a likelihood of success of the merits; (2 the existence of irreparable harm; (3 that the balance of hardships tilts in favor of injunctive relief; and (4 that granting an injunction would not harm the public interest. But when assessing whether a particular instance of trademark infringement resulted in “irreparable harm” U.S. federal courts almost uniformly presumed such irreparable harm upon a finding of likelihood of confusion. In fact, the eBay rules should not be used to eviscerate the normal presumption of irreparable harm that attaches upon a showing of liability in trademark cases. In our country when granting or denying preliminary injunction of trademark infringement cases, the plaintiff often provides a preliminary showing with regard to the existence of legal relation and trademark infringement documentary evidence, not actively providing the existence of irreparable harm, that the balance of hardships tilts in favor of injunctive relief and that an injunction is in the public interest. The court reviewing an application for preliminary injunction deliberates on the likelihood of success on the merits as the most important consideration. Compared with patent and copyright cases of the discretion of the preliminary injunction, the court mainly deliberates on the likelihood of success and the existence of irreparable harm as the most important factor. It is clear intellectual property cases, especially trademark cases on the set of preliminary injunction claim, do not require the plaintiff to take the burden of all factors of trial discretion in Taiwan. Because these harms to

  4. CCR 20th anniversary commentary: Preclinical study of proteasome inhibitor bortezomib in head and neck cancer.

    Science.gov (United States)

    Allen, Clint T; Conley, Barbara; Sunwoo, John B; Van Waes, Carter

    2015-03-01

    In a study published in the May 1, 2001, issue of Clinical Cancer Research, Sunwoo and colleagues provided evidence for proteasome inhibition of NF-κB and tumorigenesis, supporting early-phase clinical trials in solid malignancies of the upper aerodigestive tract. Subsequent clinical studies uncovered a dichotomy of responses in patients with hematopoietic and solid malignancies, and the mechanisms of resistance. ©2015 American Association for Cancer Research.

  5. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy

    NARCIS (Netherlands)

    G. Mulligan (George); D.I. Lichter (David); A.D. Bacco (Alessandra Di); S.J. Blakemore (Stephen); A. Berger (Allison); E. Koenig (Erik); H. Bernard (Hugues); W.L. Trepicchio (William); B. Li (Bin); R. Neuwirth (Rachel); N. Chattopadhyay (Nibedita); J.B. Bolen (Joseph); A.J. Dorner (Andrew); H. van de Velde (Helgi); D. Ricci (Deborah); S. Jagannath (Sundar); J.R. Berenson (James); P.G. Richardson (Paul Gerard); E.A. Stadtmauer (Edward); R.Z. Orlowski (Robert); S. Lonial (Sagar); K.C. Anderson (Kenneth); P. Sonneveld (Pieter); J.F. San Miguel (Jesús Fernando); D.-L. Esseltine (Dixie-Lee); M. Schu (Matthew)

    2014-01-01

    textabstractVarious translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41

  6. Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells

    Directory of Open Access Journals (Sweden)

    Tibullo eDaniele

    2015-10-01

    Full Text Available Osteolytic bone disease is a common manifestation of multiple myeloma (MM that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients.It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases CHIT1 and YKL40 is associated with osteoclast (OCs differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib’s concentration (BO (2.5 nM and 5nM on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to BO was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disc assay resorption pits. Silencing chitinase proteins in U266 cell line with specific siRNAs, resulted in pits number reduction on dentine discs. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients.

  7. Reversible posterior leucoencephalopathy syndrome associated with bortezomib in a patient with relapsed multiple myeloma

    NARCIS (Netherlands)

    Kager, Liesbeth M.; Kersten, Marie-Jose; Kloppenborg, Raoul Peter; van Oers, Rien; van den Born, Bert-Jan

    2009-01-01

    Reversible posterior leucoencephalopathy syndrome (RPLS) is a potentially fatal but reversible clinico-radiological syndrome with symptoms of headache, altered mental functioning, visual changes and seizures in association with typical posterior cerebral white matter lesions. RPLS is associated with

  8. Bortezomib and TRAIL : A perfect match for apoptotic elimination of tumour cells?

    NARCIS (Netherlands)

    de Wilt, L. H. A. M.; Kroon, J.; Jansen, G.; de Jong, S.; Peters, G. J.; Kruyt, F. A. E.

    Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively eradicates tumour cells via specific cell surface receptors and is intensively explored for use as a novel anticancer approach. To enhance the efficacy of TRAIL receptor agonists the proteasome inhibitor

  9. Identification of Ciprofloxacin Resistance by SimpleProbe (trademark), High Resolution Melt and Pyrosequencing (trademark) Nucleic Acid Analysis in Biothreat Agents: Bacillus anthracis, Yersinia pestis and Francisella tularensis

    Science.gov (United States)

    2010-01-01

    the opposite strand, 1 concentration of exonuclease free KlenTaq LA polymerase combined with an equal volume of TaqStart antibody (Clontech...of quinolone inhibition of DNA gyrase. Appearance of unique norfloxacin binding sites in enzymeeDNA complexes. J Biol Chem 1989;264:2973e8. [17

  10. Evaluation of a Gentex (registered trademark) ORO-NASAL Oxygen Mask for Integration with the Aqualung (registered trademark) Personal Helicopter Oxygen Delivery System (PHODS)

    National Research Council Canada - National Science Library

    Roller, Richard A; Curry, Ian P

    2008-01-01

    .... The United States Army Aeromedical Research Laboratory (USAARL) was tasked by the Product Manager Air Warrior to evaluate an oxygen mask for use with the Personal Helicopter Oxygen Delivery System (PHODS...

  11. CERT (registered trademark) Resilience Management Model (CERT (registered trademark)-RMM) V1.1: NIST Special Publication Crosswalk Version 2

    Science.gov (United States)

    2014-06-01

    27000 series, COBIT, the British Standards Institution’s BS 25999, and ISO 24762  includes quantitative process measurements that can be used to...the NIST special publications 800 series, the International Organization for Standards ( ISO ) and International Electrotechnical Commission (IEC

  12. Engineering and Scientific Applications: Using MatLab(Registered Trademark) for Data Processing and Visualization

    Science.gov (United States)

    Sen, Syamal K.; Shaykhian, Gholam Ali

    2011-01-01

    MatLab(R) (MATrix LABoratory) is a numerical computation and simulation tool that is used by thousands Scientists and Engineers in many cou ntries. MatLab does purely numerical calculations, which can be used as a glorified calculator or interpreter programming language; its re al strength is in matrix manipulations. Computer algebra functionalities are achieved within the MatLab environment using "symbolic" toolbo x. This feature is similar to computer algebra programs, provided by Maple or Mathematica to calculate with mathematical equations using s ymbolic operations. MatLab in its interpreter programming language fo rm (command interface) is similar with well known programming languag es such as C/C++, support data structures and cell arrays to define c lasses in object oriented programming. As such, MatLab is equipped with most ofthe essential constructs of a higher programming language. M atLab is packaged with an editor and debugging functionality useful t o perform analysis of large MatLab programs and find errors. We belie ve there are many ways to approach real-world problems; prescribed methods to ensure foregoing solutions are incorporated in design and ana lysis of data processing and visualization can benefit engineers and scientist in gaining wider insight in actual implementation of their perspective experiments. This presentation will focus on data processing and visualizations aspects of engineering and scientific applicati ons. Specifically, it will discuss methods and techniques to perform intermediate-level data processing covering engineering and scientifi c problems. MatLab programming techniques including reading various data files formats to produce customized publication-quality graphics, importing engineering and/or scientific data, organizing data in tabu lar format, exporting data to be used by other software programs such as Microsoft Excel, data presentation and visualization will be discussed. The presentation will emphasize creating practIcal scripts (pro grams) that extend the basic features of MatLab TOPICS mclude (1) Ma trix and vector analysis and manipulations (2) Mathematical functions (3) Symbolic calculations & functions (4) Import/export data files (5) Program lOgic and flow control (6) Writing function and passing parameters (7) Test application programs

  13. Modeling Constellation Virtual Missions Using the Vdot(Trademark) Process Management Tool

    Science.gov (United States)

    Hardy, Roger; ONeil, Daniel; Sturken, Ian; Nix, Michael; Yanez, Damian

    2011-01-01

    The authors have identified a software tool suite that will support NASA's Virtual Mission (VM) effort. This is accomplished by transforming a spreadsheet database of mission events, task inputs and outputs, timelines, and organizations into process visualization tools and a Vdot process management model that includes embedded analysis software as well as requirements and information related to data manipulation and transfer. This paper describes the progress to date, and the application of the Virtual Mission to not only Constellation but to other architectures, and the pertinence to other aerospace applications. Vdot s intuitive visual interface brings VMs to life by turning static, paper-based processes into active, electronic processes that can be deployed, executed, managed, verified, and continuously improved. A VM can be executed using a computer-based, human-in-the-loop, real-time format, under the direction and control of the NASA VM Manager. Engineers in the various disciplines will not have to be Vdot-proficient but rather can fill out on-line, Excel-type databases with the mission information discussed above. The author s tool suite converts this database into several process visualization tools for review and into Microsoft Project, which can be imported directly into Vdot. Many tools can be embedded directly into Vdot, and when the necessary data/information is received from a preceding task, the analysis can be initiated automatically. Other NASA analysis tools are too complex for this process but Vdot automatically notifies the tool user that the data has been received and analysis can begin. The VM can be simulated from end-to-end using the author s tool suite. The planned approach for the Vdot-based process simulation is to generate the process model from a database; other advantages of this semi-automated approach are the participants can be geographically remote and after refining the process models via the human-in-the-loop simulation, the system can evolve into a process management server for the actual process.

  14. Design of a Prototype Autonomous Amphibious WHEGS(Trademark) Robot for Surf-Zone Operations

    National Research Council Canada - National Science Library

    Ward, Jason L

    2005-01-01

    .... This platform, in conjunction with a commercial-off- the-shelf (COTS) control architecture, is capable of autonomous, land based waypoint navigation, self orientation, and rudimentary obstacle avoidance...

  15. System 80+{trademark} standard design: CESSAR design certification. Volume 5: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report has been prepared in support of the industry effort to standardize nuclear plant designs. The documents in this series describe the Combustion Engineering, Inc. System 80+{sup TM} Standard Design.

  16. Amelioration of Radiation-Induced Hematopoietic and Gastrointestinal Damage by Ex-RAD (trademark) in Mice

    Science.gov (United States)

    2012-06-06

    concern in therapeutic radiology [1]. Other instances of radiation exposure include accidents that can occur in nuclear power plants, potential terrorist...prevention. In: Ricks RC, Berger ME, O’Hara FM (eds). The Medical Basis for Radiation Accident Preparedness: The Clinical Care of Victims. Boca Raton...Hovdenak N., Fajardo LF, Hauer-Jensen M. Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy . Int J Radiat Oncol

  17. Effect of X-Rays on the Mechanical Properties of Aluminized FEP Teflon(trademark)

    Science.gov (United States)

    Gaier, James R.; Brinkmeier, Michael R.; Gaier, Elizabeth M.

    1999-01-01

    Pieces of the multilayer insulation (MLI) that is integral to the thermal control of the Hubble Space Telescope (HST) have been returned by two servicing missions after 3.6 and 6.8 years in orbit. They reveal that the outer layer, which is made from 5 mil (0.13 mm) thick aluminized fluorinated ethylenepropylene (FEP) Teflon. has become severely embrittled. Although possible agents of this embrittlement include electromagnetic radiation across the entire solar spectrum, trapped particle radiation, atomic oxygen, and thermal cycling, intensive investigations have not yielded unambiguous causes. Previous studies utilizing monoenergetic photons in the 69-1900 eV range did not cause significant embrittlement, even at much higher doses than were experienced by the HST MLI. Neither did x-rays in the 3 to 10 keV range generated in a modified electron bean evaporator. An antidotal aluminized FEP sample that was exposed to an intensive dose from unfiltered Mo x-ray radiation from a rotating anode generator, however, did show the requisite embrittlement. Thus, a study was undertaken to determine the effects of x-ray exposure on the embrittlement of aluminized FEP in hopes that it might elucidate the HST MLI degradation mechanism. Tensile specimens of aluminized 5 mil thick FEP were exposed to a constant fluence of unfiltered x-ray radiation from a Mo target whose maximum energy ranged from 20-60 kV. Other samples were annealed, thermally cycled (100x) between 77-333 K, or cycled and irradiated. Tensile tests and density measurements were then performed on the samples. Only the samples which had been irradiated had the drastically reduced elongation-to-break, characteristic of the HST samples. Thermal cycling may accelerate the embrittlement, but the effect was near the scatter in the measurements. Annealing and thermal cycling had no apparent effect. Only the samples which had been irradiated and annealed showed significant density increases, likely implicating polymer chain scission and annealing.

  18. IMCOM LonWorks (registered trademark) Building Automation Systems Implementation Strategy

    National Research Council Canada - National Science Library

    Schwenk, David M; Bush, Joseph; Hughes, Lucie M; Briggs, Stephen; White, Will

    2008-01-01

    Army Installations often expand their use of digital control systems for heating, ventilating, and air conditioning and other mechanical and electrical building systems on a building-by-building basis...

  19. LEED (Trademark) for Homes - Pilot Study: Evaluation for Use in Army Family Housing

    Science.gov (United States)

    2007-11-01

    Exchange Cafeteria, Fast Food/Snack Bar (Cyber Cafe , Food Court, Burger King, Popeyes, etc.), Post (Installation) Dining Facilities School Dependent...Water-efficient showerhead with H2Okinetic technology from Delta • WeatherTRAK smart irrigation controls from HydroPoint Data Sys- tems, Inc...worship (protestant, catholic, Jewish), restaurant (food court, Burger King, combined club), other neighborhood-serving retail (cyber cafe , military

  20. Near Net Shape Rapid Manufacture & Repair by LENS(registered trademark)

    Science.gov (United States)

    2006-05-01

    manufactured from advanced materials such as titanium alloys, superalloys or special steels are critical to the performance of the armed forces...parts, in a wide array of alloys including titanium, nickel, cobalt , steel and novel materials such as Metal Matrix Composites and Functionally...Steels 304, 316, 420 Nickel Based Hastelloy X Aluminium 4047 Cobalt Base CoCr (Stellite) Copper Cu-Ni LENS Developmental Alloys Alloy Class Alloy

  1. 77 FR 64189 - Changes to Representation of Others Before the United States Patent and Trademark Office

    Science.gov (United States)

    2012-10-18

    ... practice before the Office into closer conformity with the Rules of Professional Conduct adopted by nearly... representation of a client constitutes an endorsement of the client's political, economic, social, or moral views... practitioners to maintain client trust account records in electronic, photographic, computer or other media or...

  2. 78 FR 20179 - Changes to Representation of Others Before The United States Patent and Trademark Office

    Science.gov (United States)

    2013-04-03

    ..., Inc., 375 F.3d 1341, 1358 (Fed. Cir. 2004); In re Spalding Sports Worldwide, Inc., 203 F.3d 800, 807..., economic, social, or moral views or activities. Section 11.103 addresses the practitioner's duty to act... improperly with respect to aspects of the dispute. It is not intended to provide direct access on routine...

  3. Recent Updates to SWANFAR (registered trademark), a 5DVAR Data Assimilation System for SWAN

    Science.gov (United States)

    2016-11-10

    system at different stages are presented, followed by discussion of the advantages and limitations of spectral data assimilation built upon the SWAN...will only use ipr*jpr for 1D tiling): export ipr=4 export jpr=2 # # cycle parameters export ITERMAX=5 ## maximum number of CG...iterations export CRDATE=2013071100 ## start date export CRDATE0=$CRDATE ## preserve orig start date export ENDDTG=2013071200 ## end date export

  4. ASSESSMENT OF PRESENCE AND LEACHING TOXIC METALS IN SAMPLES OF THREE TRADEMARKS OF ALGINATES

    Directory of Open Access Journals (Sweden)

    Fabíole Jordana Los

    2013-07-01

    Full Text Available A material widely used in dental offices for making dental impressions is alginate. The objective of this work was to study three different brands of alginate by fluorescence and X-ray diffraction and extractions using the method of Tessier, followed by the determination of the concentrations of metals in the extracts by atomic absorption spectrometry. Through X-ray fluorescence, was observed that the most representative in the samples are Si, Ca, K, S, Al, Mg, Fe and P, and the sum of these elements reaches values above 97%. By X-ray diffraction, it was observed that the peak was indicative of a higher concentration of SiO2 (cristobalite and the compounds found in all specimens were CaSO4.2H2O, SiO2 (cristobalite and SiO 2. The assessment of mobilization (leaching of metals performed by the method of Tessier and its comparison with the CONAMA 430/11 has shown potential risks of improper disposal of such material in the environment due to concentrations (above PMV of lead in the fractions of the metal on the carbonates and organic matter.

  5. Formalization and Transformation of Informal Analysis Models into Executive REFINE (trademark) Specifications

    Science.gov (United States)

    1992-12-01

    REFINE, and her dynamite oatmeal- chocolate -chip cookie recipe. I also owe many thanks to my family for their support (and pretending to understand my... proceso e. Return tuple -n vaeld, [next-proceeses> asscirmaeon w atI t Returns Returns Tuple lNext ProcpseName 1. Execute all ruleas whose

  6. UNIX trademark in high energy physics: What we can learn from the initial experiences at Fermilab

    Energy Technology Data Exchange (ETDEWEB)

    Butler, J.N.

    1991-03-01

    The reasons why Fermilab decided to support the UNIX operating system are reviewed and placed in the content of an overall model for high energy physics data analysis. The strengths and deficiencies of the UNIX environment for high energy physics are discussed. Fermilab's early experience in dealing with a an open'' multivendor environment, both for computers and for peripherals, is described. The human resources required to fully exploit the opportunities are clearly growing. The possibility of keeping the development and support efforts within reasonable bounds may depend on our ability to collaborate or at least to share information even more effectively than we have in the past. 7 refs., 4 figs., 5 tabs.

  7. Reaping the benefits of evolutionary critical technology development - system 80+trademark standardized plant design

    International Nuclear Information System (INIS)

    Matzie, R.A.; Davis, G.A.; Bagnal, C.W. Jr.; Turk, R.S.

    1993-01-01

    Light water reactors have proved themselves to be a critical part of the electrical power generation infrastructure in the United States as well as in the world. As society moves to improve the safety and economical viability of our critical technologies, we must decide the most beneficial means of making those improvements. In some cases, the critical technologies are propelled in a single leap; in others, it is the result of a continuous and deliberate series of carefully chosen steps. ABB Nuclear Systems was faced with making such a choice in the development of nuclear power plant technology. We elected to focus our development and commercialization efforts on the evolutionary System 80+ Advanced Standardized plant design. Obviously, this was because we have a strong indication that this would be the most beneficial way to meet customers' needs and reap the largest possible benefit from the development of these critical technologies. The evolutionary approach to critical technology development requires a reliance on making incremental improvements over time to the technology. This has the benefit of providing the following: 1. predictable performance based on experience, 2. enhanced safety, performance, economics 3. incremental changes in technology, 4. availability of proven equipment and systems, and 5. assured acceptance and licensability

  8. Integration of NASA-Developed Lifing Technology for PM Alloys into DARWIN (registered trademark)

    Science.gov (United States)

    McClung, R. Craig; Enright, Michael P.; Liang, Wuwei

    2011-01-01

    In recent years, Southwest Research Institute (SwRI) and NASA Glenn Research Center (GRC) have worked independently on the development of probabilistic life prediction methods for materials used in gas turbine engine rotors. The two organizations have addressed different but complementary technical challenges. This report summarizes a brief investigation into the current status of the relevant technology at SwRI and GRC with a view towards a future integration of methods and models developed by GRC for probabilistic lifing of powder metallurgy (P/M) nickel turbine rotor alloys into the DARWIN (Darwin Corporation) software developed by SwRI.

  9. HOGEN{trademark} proton exchange membrane hydrogen generators: Commercialization of PEM electrolyzers

    Energy Technology Data Exchange (ETDEWEB)

    Smith, W.F.; Molter, T.M. [Proton Energy Systems, Inc., Rocky Hill, CT (United States)

    1997-12-31

    PROTON Energy Systems` new HOGEN series hydrogen generators are Proton Exchange Membrane (PEM) based water electrolyzers designed to generate 300 to 1000 Standard Cubic Feet Per Hour (SCFH) of high purity hydrogen at pressures up to 400 psi without the use of mechanical compressors. This paper will describe technology evolution leading to the HOGEN, identify system design performance parameters and describe the physical packaging and interfaces of HOGEN systems. PEM electrolyzers have served US and UK Navy and NASA needs for many years in a variety of diverse programs including oxygen generators for life support applications. In the late 1970`s these systems were advocated for bulk hydrogen generation through a series of DOE sponsored program activities. During the military buildup of the 1980`s commercial deployment of PEM hydrogen generators was de-emphasized as priority was given to new Navy and NASA PEM electrolysis systems. PROTON Energy Systems was founded in 1996 with the primary corporate mission of commercializing PEM hydrogen generators. These systems are specifically designed and priced to meet the needs of commercial markets and produced through manufacturing processes tailored to these applications. The HOGEN series generators are the first step along the path to full commercial deployment of PEM electrolyzer products for both industrial and consumer uses. The 300/1000 series are sized to meet the needs of the industrial gases market today and provide a design base that can transition to serve the needs of a decentralized hydrogen infrastructure tomorrow.

  10. Software engineering and Ada (Trademark) training: An implementation model for NASA

    Science.gov (United States)

    Legrand, Sue; Freedman, Glenn

    1988-01-01

    The choice of Ada for software engineering for projects such as the Space Station has resulted in government and industrial groups considering training programs that help workers become familiar with both a software culture and the intricacies of a new computer language. The questions of how much time it takes to learn software engineering with Ada, how much an organization should invest in such training, and how the training should be structured are considered. Software engineering is an emerging, dynamic discipline. It is defined by the author as the establishment and application of sound engineering environments, tools, methods, models, principles, and concepts combined with appropriate standards, guidelines, and practices to support computing which is correct, modifiable, reliable and safe, efficient, and understandable throughout the life cycle of the application. Neither the training programs needed, nor the content of such programs, have been well established. This study addresses the requirements for training for NASA personnel and recommends an implementation plan. A curriculum and a means of delivery are recommended. It is further suggested that a knowledgeable programmer may be able to learn Ada in 5 days, but that it takes 6 to 9 months to evolve into a software engineer who uses the language correctly and effectively. The curriculum and implementation plan can be adapted for each NASA Center according to the needs dictated by each project.

  11. 76 FR 13987 - Submissions Regarding Correspondence and Regarding Attorney Representation (Trademarks)

    Science.gov (United States)

    2011-03-15

    ... Representative's Address (Paper) 10 13 2 TEAS Change of Domestic Representative's Address (TEAS Global).. 5 250... and businesses that use, or intend to use such marks in commerce may file an application to register... the registration files the necessary maintenance documents. Such individuals and businesses may also...

  12. An Integrated Hydrofoil and Propeller Design Tool for the Window (Trademark) Environment

    Science.gov (United States)

    1996-06-01

    return msg.wParam; p 4 When viewed for the first time, and particularly without the benefit of experience with the C programming language, the logic...origin~jrpbhx+270*BANGINUIjIOfl* width640.); pointuljy - I(intX(orgn- gmo -rpby+((max -thick-BTHKINiI[OI)/ delta dzck)*40)*heigbt43O.0); Euip~eBaMdediniDC...DiIgcbme) //ucrqp tM e rig umin whil (sexlcharil3&A xwclbat10) mexiche - gec(blade); I/red W. the anUmber at components hcauqbladetlW,&LDEV); //$ crop the

  13. EVALUATION OF SPERM CHROMATIN STRUCTURE ASSAY (SCSA REGISTERED TRADEMARK) IN HUMAN SPERM AFTER SIMULATED OVERNIGHT SHIPMENT

    Science.gov (United States)

    Home semen collection kits allow men to collect a sample at their convenience and send it via overnight mail to the laboratory. Benefits of this approach include facilitated sample collection from different geographic locations, minimized variability through analysis by a central...

  14. Manned Certification Evaluation of the Innerspace Systems (registered trademark) Megalodon Underwater Breathing Apparatus

    Science.gov (United States)

    2010-12-01

    divers participated in each OSF test dive. Divers dressed for thermal comfort ranging from swimsuits and t- shirts to wet suit; one diver wore a dry suit...and t- shirts or wet suits.7,8 Five minutes before the end of the planned bottom time, divers stopped ergometer work and assumed a relaxed...PO2, all analyzed dives (n=61) TWA PO2 Bottom Time TWA PO2 post- OS TWA PO2 dive Min 1.35 1.33 1.32 Median 1.41 1.38 1.37 Mean 1.43 1.39 1.37 Max

  15. Supporting the Use of CERT (registered trademark) Secure Coding Standards in DoD Acquisitions

    Science.gov (United States)

    2012-07-01

    Engineering Institute) John Bergey (Software Engineering Institute) Philip Miller (Carnegie Mellon University and ClickMedix LLC) July 2012...Standards in DoD Acquisitions 5. FUNDING NUMBERS FA8721-05-C-0003 6. AUTHOR(S) Tim Morrow, Robert Seacord, John Bergey , Philip Miller 7. PERFORMING

  16. Program Accreditation and the Graduate Reference Curriculum in Systems Engineering (GRCSE (trademark))

    Science.gov (United States)

    2012-07-01

    variables , and discrete mathematics. The curriculum for programs containing the modifier ―computer‖ in the title must include discrete mathematics...Engineer consultant to Lockheed Martin, IBM, and EDO Ceramics, for ASSETT. Dr. Squires holds INCOSE CSEP, CSEP-Acquisition certifications

  17. Passive Autonomous Acoustic Monitoring of Marine Mammals: System Development Using Seaglider (Trademark)

    Science.gov (United States)

    2015-01-30

    same sensor on a Slocum glider from Teledyne Webb Research, work that has been reported separately. Hardware and software modifications were made to...adapts instruments and glider behavior to support specific Navy mission requirements. This group is informally called the Applied Seaglider Group...axis carries various scales, but for the red curve, which is glider depth, each tick mark is 20 meters. Seaglider S/N 178 was ballasted light for

  18. System 80+{trademark} Standard Design: CESSAR design certification. Volume 2: Amendment I

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-21

    This report, entitled Combustion Engineering Standard Safety Analysis Report - Design Certification (CESSAR-DC), has been prepared in support of the industry effort to standardize nuclear plant designs. These documents describe the Combustion Engineering, Inc. System 80+{sup TM} Standard Design. This report, Volume 2, in conjunction with Volume 3, provides the design of structures, components, equipment and systems.

  19. Post-Retention Changes in Class II Correction With the Forsus (trademark) Appliance

    Science.gov (United States)

    2015-06-01

    ForsusTM appliance. Methods: 40 Class II patients (25 males , 15 females) consecutively treated with the ForsusTM appliance had cephalometric radiographs...was taken. Sample Population The 40 patients (25 male , 15 female) treated with the ForsusTM in conjunction with fixed appliances for a mean...range of values were caused by the experimental group 46 containing individuals who were treated early (i.e. before puberty ) and those who were

  20. Introducing the CERT (Trademark) Resiliency Engineering Framework: Improving the Security and Sustainability Processes

    National Research Council Canada - National Science Library

    Caralli, Richard A; Stevens, James F; Wallen, Charles M; White, David W; Wilson, William R; Young, Lisa R

    2007-01-01

    ... and controlling operational resiliency. Unfortunately, organizations often manage these activities in a reactive posture fraught with stove-piped organizational structures and poorly defined and measured goals. The result...