Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

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Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

2014-05-01

Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

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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

The Aesthetics Of Trademarks

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Peter H. Karlen

2008-01-01

Full Text Available Trademarks are not just property, they are aesthetic creations that pervade everyday experience. One estimate is that the average person encounters more than 1,000 trademarks per day, many of which influence purchases and product use. As pervasive aesthetic creations having literary, pictorial, graphic, sculptural, and musical content, trademarks deserve aesthetic analysis. The article discusses the origins, strength, appeal, and effectiveness of trademarks within the context of aesthetic considerations such as meaning, intention, authorship, and mode of creation. Also reviewed are morphemic and phonemic analysis of trademarks, semantic positioning, the dichotomy between creation and discovery of trademarks, and the differences between trademarks and titles. The discussion is confined to "word marks" consisting of alphanumeric characters, since discussing other kinds of marks (such as designs, configurations, sounds, colors, and scents would raise issues well beyond the scope of a single article.

A phase I trial of bortezomib and interferon-α-2b in metastatic melanoma.

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Markowitz, Joseph; Luedke, Eric A; Grignol, Valerie P; Hade, Erinn M; Paul, Bonnie K; Mundy-Bosse, Bethany L; Brooks, Taylor R; Dao, Thao-Vi; Kondalasula, Sri V; Lesinski, Gregory B; Olencki, Thomas; Kendra, Kari L; Carson, William E

2014-01-01

The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-α-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients.

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline

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Reece, D.; Imrie, K.; Stevens, A.; Smith, C.A.

2006-01-01

Questions In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate? What is the toxicity associated with the use of bortezomib? Which patients are more or less likely to benefit from treatment with bortezomib? Perspectives Evidence was selected and reviewed by two members of the Hemato...

Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

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Valentina A Carozzi

Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

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

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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).

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

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Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.

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Philippe, Laure; Ceroi, Adam; Bôle-Richard, Elodie; Jenvrin, Alizée; Biichle, Sabeha; Perrin, Sophie; Limat, Samuel; Bonnefoy, Francis; Deconinck, Eric; Saas, Philippe; Garnache-Ottou, Francine; Angelot-Delettre, Fanny

2017-11-01

Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematologic malignancy with a poor prognosis. No consensus regarding optimal treatment modalities is currently available. Targeting the nuclear factor-kappa B pathway is considered a promising approach since blastic plasmacytoid dendritic cell neoplasm has been reported to exhibit constitutive activation of this pathway. Moreover, nuclear factor-kappa B inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines, achieved using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib, interferes in vitro with leukemic cell proliferation and survival. Here we extended these data by showing that primary blastic plasmacytoid dendritic cell neoplasm cells from seven patients were sensitive to bortezomib-induced cell death. We confirmed that bortezomib efficiently inhibits the phosphorylation of the RelA nuclear factor-kappa B subunit in blastic plasmacytoid dendritic cell neoplasm cell lines and primary cells from patients in vitro and in vivo in a mouse model. We then demonstrated that bortezomib can be associated with other drugs used in different chemotherapy regimens to improve its impact on leukemic cell death. Indeed, when primary blastic plasmacytoid dendritic cell neoplasm cells from a patient were grafted into mice, bortezomib treatment significantly increased the animals' survival, and was associated with a significant decrease of circulating leukemic cells and RelA nuclear factor-kappa B subunit expression. Overall, our results provide a rationale for the use of bortezomib in combination with other chemotherapy for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm. Based on our data, a prospective clinical trial combining proteasome inhibitor with classical drugs could be envisaged. Copyright© Ferrata Storti Foundation.

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

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Reece, D; Imrie, K; Stevens, A; Smith, C A

2006-10-01

In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?What is the toxicity associated with the use of bortezomib?Which patients are more or less likely to benefit from treatment with bortezomib? Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback. Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events. A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc. The literature review found one randomized controlled trial (rct)-the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma. The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is

THE NOTORIOUS, REPUTED AND FAMOUS TRADEMARKS

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Andreea LIVĂDARIU

2015-07-01

Full Text Available The owner of a trademark that has a reputation in Romania or in the European Union may request to court to forbid the infringer from using, without its consent, a sign identical or similar to its trademark, but for products or services different from those which are sold or provided under said trademark. According to Law no. 84/1998, the notorious (well-known trademark is the trademark which does not necessarily have to be registered under the Trademark law protection. The Romanian doctrine sustains that famous trademarks do exist. In this paper, we shall attempt to find (if it really does exist the difference between notorious (well-known, reputed and famous trademarks, the criteria by means of which these trademarks shall be distinguished and the evidence by means of which the notoriety, reputation or fame of a trademark may be argued. We shall also present the legal regime and our analysis will be based on the Trademark law, doctrine and case-law studies.

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

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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.

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

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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.

Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study.

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Oriol, Albert; Giraldo, Pilar; Kotsianidis, Ioannis; Couturier, Catherine; Olie, Robert; Angermund, Ralf; Corso, Alessandro

2015-08-01

Multiple myeloma remains incurable and retreatment with available therapies is of substantial interest. This retrospective observational study included data from 35 patients treated initially and at the first relapse with bortezomib-containing regimens. Bortezomib retreatment provided a similar depth and time to response as first-line therapy; however, as could be expected, the duration of response was shorter with retreatment. The tolerability profile was similar with bortezomib as the first- and second-line therapy, with no evidence of cumulative toxicity. These findings support bortezomib retreatment after a treatment-free interval of ≥6 months in patients who achieved at least a partial response to the first-line bortezomib-based therapy.

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

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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.

Bortezomib-induced acute pancreatitis: Case report and review of the literature.

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Talamo, Giampaolo; Sivik, Jeffrey; Pandey, Manoj K; Mir, Muhammad A

2016-04-01

Acute pancreatitis is a rare complication of chemotherapy agents. We describe the case of a patient with multiple myeloma who developed acute pancreatitis after treatment with bortezomib, a proteasome inhibitor commonly used in the treatment of this disease. We reviewed the available medical literature on this topic, and found other seven similar cases, all after intravenous bortezomib. Our case is the first one occurring with the subcutaneous route of administration. © The Author(s) 2014.

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

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Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong; Gu, Yanhong; Shu, Yongqian; Sun, Yang; Shen, Yan; Xu, Qiang

2015-01-01

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

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

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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.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

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Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

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

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

Sequential Exposure of Bortezomib and Vorinostat is Synergistic in Multiple Myeloma Cells

Science.gov (United States)

Nanavati, Charvi; Mager, Donald E.

2018-01-01

Purpose To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. Methods U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures. p21 and cleaved PARP were measured using immunoblotting to assess critical biomarker dynamics. For xenografts, data were extracted from literature and modeled with a PK/PD model with an interaction parameter. Results Estimated model parameters for simultaneous in vitro and xenograft treatments suggested additive drug effects. The sequence of bortezomib preincubation for 24 hours, followed by vorinostat for 24 hours, resulted in an estimated interaction term significantly less than 1, suggesting synergistic effects. p21 and cleaved PARP were also up-regulated the most in this sequence. Conclusions Semi-mechanistic pharmacodynamic modeling suggests synergistic pharmacodynamic interactions for the sequential administration of bortezomib followed by vorinostat. Increased p21 and cleaved PARP expression can potentially explain mechanisms of their enhanced effects, which require further PK/PD systems analysis to suggest an optimal dosing regimen. PMID:28101809

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

An effective modestly intensive re-induction regimen with bortezomib in relapsed or refractory paediatric acute lymphoblastic leukaemia.

Science.gov (United States)

Kaspers, Gertjan J L; Niewerth, Denise; Wilhelm, Bram A J; Scholte-van Houtem, Peggy; Lopez-Yurda, Marta; Berkhof, Johannes; Cloos, Jacqueline; de Haas, Valerie; Mathôt, Ron A; Attarbaschi, Andishe; Baruchel, André; de Bont, Eveline S; Fagioli, Franca; Rössig, Claudia; Klingebiel, Thomas; De Moerloose, Barbara; Nelken, Brigitte; Palumbo, Giuseppe; Reinhardt, Dirk; Rohrlich, Pierre-Simon; Simon, Pauline; von Stackelberg, Arend; Zwaan, Christian Michel

2018-05-01

This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m 2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure. Most common grade 3-4 toxicities were febrile neutropenia (31%) and pain (17%). Bortezomib was safely combined with vincristine. Bortezomib rarely penetrated the cerebrospinal fluid. © 2018 John Wiley & Sons Ltd.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma

Science.gov (United States)

Kim, George P.; Mahoney, Michelle R.; Szydlo, Daniel; Mok, Tony S. K.; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C.; Rubin, Joseph; Philip, Philip A.; Nowak, Anna; Wright, John J.; Erlichman, Charles

2013-01-01

Summary Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. PMID:20839030

Inhibition of inducible heat shock protein-70 (hsp72 enhances bortezomib-induced cell death in human bladder cancer cells.

Directory of Open Access Journals (Sweden)

Wei Qi

Full Text Available The proteasome inhibitor bortezomib (Velcade is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1 to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation-specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low cell lines (UM-UC10 and UM-UC13, and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B further sensitized these cells to bortezomib, and exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo. Together, our results provide proof-of-concept for using Hsp72 inhibitors to promote bortezomib sensitivity in bladder cancers and suggest that selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promoter methylation.

Are trademarks a valid indicator of innovation? : results of an in-depth study of new Benelux trademarks filed by SMEs

NARCIS (Netherlands)

Flikkema, M.; De Man, A.P.; Castaldi, C.

2014-01-01

This paper extends the emerging literature on the value of trademarks for innovation studies and policy-making with the first empirical study at the trademark level. It gives a view on how companies use trademarks and interpret trademark activities. A sample of 660 new Benelux trademarks registered

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.

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

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.

Are Trademark Counts a Valid Indicator of Innovation? Results of an In-Depth Study of New Benelux Trademarks Filed by SMEs.

NARCIS (Netherlands)

Flikkema, M.J.; de Man, A.P.; Castaldi, C.

2014-01-01

This paper extends the emerging literature on the value of trademarks for innovation studies and policy-making with the first empirical study at the trademark level. It gives a view on how companies use trademarks and interpret trademark activities. A sample of 660 new Benelux trademarks registered

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

BMC{trademark}: Baseline report

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-07-31

Barrier Membrane Containment (BMC){trademark} is a high-density polyethylene membrane (HOPE) groundwater barrier and pass-through system, with applications ranging from plume control and containment to groundwater manipulation coupled with in-site treatment. BMC{trademark} system can function as a permeable or impermeable reaction wall, a cut-off wall, interceptor trenches, a barrier with collection and/or monitoring system and a pass-through in a funnel and gate configuration. BMC{trademark} can be inspected with a down-hole video camera, producing a permanent VHS format tape, insuring the integrity of the wall and the interlocking joints. The joints are sealed with a ``U``-packing elastomeric gasket to prevent the flow of fluids or gases.

Aspects of National and Community Trademarks

Directory of Open Access Journals (Sweden)

Constantin Anechitoae

2012-05-01

Full Text Available When Romania joined the EU on January 1, 2007, all Community trademarks (CTM, with thefiling date before that date, were automatically extended and have effects in Romania. National brands do notextend across the EU. In order to obtain a Community trade mark, a single application is filled in at OHIM. Itcan convert a Community trade mark application into national trade mark. The registered community trademark has effect in all EU Member States, including Romania. The national trademarks registered nationally -at the State Office for Inventions and Trademarks (OSIM - are effective only in Romania and have no effectin the European Community.

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...

Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

Science.gov (United States)

Patel, Kinjal; Dillon, John J; Leung, Nelson; Bomback, Andrew S; Appel, Gerald B; D'Agati, Vivette; Canetta, Pietro A

2014-07-01

Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

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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.

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 ...

An Interdisciplinary Inquiry into the Foundations of Trademark Law

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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.

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 cycles...... from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P...... with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival....

Praktik Trademark Squatting dalam Proses Pendaftaran Merek di Indonesia

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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

Development of acute pulmonary hypertension after bortezomib treatment in a patient with multiple myeloma: a case report and the review of the literature.

Science.gov (United States)

Akosman, Cengiz; Ordu, Cetin; Eroglu, Elif; Oyan, Basak

2015-01-01

Bortezomib is widely used in treatment of multiple myeloma. In recent years, severe bortezomib-induced lung injury has been reported. The clinical course is generally characterized with fever and dyspnea, followed by respiratory failure with pulmonary infiltrates. Herein, we report a 57-year-old man with newly diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the third day of the first dose of bortezomib therapy. He had bilateral jugular venous distention, crackles at the bases of the lungs and hepatomegaly. Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary embolism, and microbiological examination was negative. On his course, fever, dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden onset of PH and its rapid decrement without any treatment suggests bortezomib as the underlying cause. Subsequently, the patient did not respond to vincristine-doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was repeated, and no pulmonary adverse reactions occurred. Follow-up echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm Hg. To our knowledge, this is the first case of acute PH after front-line bortezomib therapy. In this report, we review bortezomib-related pulmonary complications in the literature and possible underlying mechanisms.

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

with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression...

WIPO Publishes Guide to Trademarks for Business

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Entrepreneurs and managers of small andmedium-sized enterprises(SMEs)can nowconsult a World Intellectual PropertyOrganization(WIPO)publication thatexplains the basics of trademarks from abusiness perspective.The guide,entitled"Making a Mark:An Introduction toTrademarks for Small and Medium-sizedEnterprises",is intended to enhance thereader's understanding of the strategic valueof trademarks in business planning.It is the

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.

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.

TRADEMARK IMAGE RETRIEVAL USING LOW LEVEL FEATURE EXTRACTION IN CBIR

OpenAIRE

Latika Pinjarkar*, Manisha Sharma, Smita Selot

2016-01-01

Trademarks work as significant responsibility in industry and commerce. Trademarks are important component of its industrial property, and violation can have severe penalty. Therefore designing an efficient trademark retrieval system and its assessment for uniqueness is thus becoming very important task now a days. Trademark image retrieval system where a new candidate trademark is compared with already registered trademarks to check that there is no possibility of resembl...

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

Science.gov (United States)

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

Science.gov (United States)

Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

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.)

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.

Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib.

Science.gov (United States)

Podratz, Jewel L; Kulkarni, Amit; Pleticha, Josef; Kanwar, Rahul; Beutler, Andreas S; Staff, Nathan P; Windebank, Anthony J

2016-03-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL/6J, DBA/2J, BALB/cJ, and C3H/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL/6J and Balb/cJ DRG-NOG was more sensitive to cisplatin than DBA/2J and C3H/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA/2J and C3H/H3J mice. C57BL/6J DRG-NOG was most sensitive and Balb/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Garg, Amit; Morgunskyy, Mykhaylo; Belagali, Yogesh; Gupta, Namita; Akku, Shyam Prasad

2016-01-01

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 May 19, 2016 focusing on MM management, bortezomib role, unmet medical needs, and current challenges. The health-care system for oncology in India is majorly private vs. 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 health-care access, need immediate attention. High-quality generics access will improve outcomes and support health-care cost containment. Pharmacoeconomic studies and head-to-head trials are warranted to determine the cost-effectiveness and benefit of novel therapies in MM.

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.

The efficacy and safety of the PAD regimen (bortezomib, doxorubicin, dexamethasone) in the treatment of plasma cell leukemia

International Nuclear Information System (INIS)

Kraj, M.; Poglod, R.; Szpila, T.; Warzocha, K.

2009-01-01

Plasma cell leukemia (PCL) represents the most aggressive variant of multiple myeloma that requires establishing new treatment approaches. Here, we report 4 patients with PCL treated with bortezomib. In 3 patients primary PCL and in one - secondary PCL was diagnosed. Two patients had previously received 2 to 4 lines of chemotherapy, including thalidomide and two patients received only VAD treatment. Bortezomib was given according to the standard schedule of 1.3 mg/m 2 days 1,4,8,11 with an interval of 10 days between the cycles. Three patients received doxorubicin 9 mg/m2 and dexamethasone 40 mg on days 1-4 of cycle in combination with bortezomib (PAD regimen). In the first patient with primary PCL (with bone marrow plasma cell ratio - 80%, absolute peripheral blood plasma cell count- 3.7 x 10 9 /L cells, IgGλ serum monoclonal protein 8.5 g/dL and osteolysis) bortezomib was administered twice as an induction therapy and was re-administered in relapse. A near complete remission (disappearance of circulating and bone marrow plasma cells, disappearance of M-component at electrophoresis but positive immunofixation) was achieved subsequently to induction PAD treatment. In this patient herpes zoster and neurological grade 2 toxicity was observed. Following cyclophosphamide 4.9 g and G-CSF, peripheral blood stem cells were successfully (8.0 x 10 6 CD34 + cells/kg) harvested. After melphalan 200 mg/m 2 peripheral blood autologous stem cell transplantation (PBASCT) was performed. The time to neutrophil > 0.5 x 10 9 /L engraftment was 20 days and the time to platelet count > 20 x 10 9 /L was 17 days. PBASCT led to complete remission which lasted 7 months. Partial remission was achieved subsequently to PCL relapse retreatment with PAD which was accompanied by hematological toxicity, infections and aggravation of peripheral sensory neuropathy. The patient died of progressive disease 27 months from PCL diagnosis and 8 months from its recurrence. In the second case of primary

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

...; it affords the broad-spectrum decontamination of chemical and biological warfare agents. Composed entirely of ingredients commonly found in cosmetics, detergents, laundry boosters, and vitamins, Decon Green (trademark...

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.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

Science.gov (United States)

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

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.

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...

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

Numerical benchmarking of SPEEDUP trademark against point kinetics solutions

International Nuclear Information System (INIS)

Gregory, M.V.

1993-02-01

SPEEDUP trademark is a state-of-the-art, dynamic, chemical process modeling package offered by Aspen Technology. In anticipation of new customers' needs for new analytical tools to support the site's waste management activities, SRTC has secured a multiple-user license to SPEEDUP trademark. In order to verify both the installation and mathematical correctness of the algorithms in SPEEDUP trademark, we have performed several numerical benchmarking calculations. These calculations are the first steps in establishing an on-site quality assurance pedigree for SPEEDUP trademark. The benchmark calculations consisted of SPEEDUP trademark Version 5.3L representations of five neutron kinetics benchmarks (each a mathematically stiff system of seven coupled ordinary differential equations), whose exact solutions are documented in the open literature. In all cases, SPEEDUP trademark solutions to be in excellent agreement with the reference solutions. A minor peculiarity in dealing with a non-existent discontinuity in the OPERATION section of the model made itself evident

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)

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

Science.gov (United States)

Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

2013-03-15

This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

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...

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

Science.gov (United States)

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

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

Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro.

Science.gov (United States)

Hu, Jinsong; Van Valckenborgh, Els; Xu, Dehui; Menu, Eline; De Raeve, Hendrik; De Bruyne, Elke; De Bryune, Elke; Xu, Song; Van Camp, Ben; Handisides, Damian; Hart, Charles P; Vanderkerken, Karin

2013-09-01

Recently, we showed that hypoxia is a critical microenvironmental factor in multiple myeloma, and that the hypoxia-activated prodrug TH-302 selectively targets hypoxic multiple myeloma cells and improves multiple disease parameters in vivo. To explore approaches for sensitizing multiple myeloma cells to TH-302, we evaluated in this study the antitumor effect of TH-302 in combination with the clinically used proteasome inhibitor bortezomib. First, we show that TH-302 and bortezomib synergistically induce apoptosis in multiple myeloma cell lines in vitro. Second, we confirm that this synergism is related to the activation of caspase cascades and is mediated by changes of Bcl-2 family proteins. The combination treatment induces enhanced cleavage of caspase-3/8/9 and PARP, and therefore triggers apoptosis and enhances the cleavage of proapoptotic BH3-only protein BAD and BID as well as the antiapoptotic protein Mcl-1. In particular, TH-302 can abrogate the accumulation of antiapoptotic Mcl-1 induced by bortezomib, and decreases the expression of the prosurvival proteins Bcl-2 and Bcl-xL. Furthermore, we found that the induction of the proapoptotic BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA is associated with this synergism. In response to the genotoxic and endoplasmic reticulum stresses by TH-302 and bortezomib, the expression of PUMA and NOXA were upregulated in p53-dependent and -independent manners. Finally, in the murine 5T33MMvv model, we showed that the combination of TH-302 and bortezomib can improve multiple disease parameters and significantly prolong the survival of diseased mice. In conclusion, our studies provide a rationale for clinical evaluation of the combination of TH-302 and bortezomib in patients with multiple myeloma.

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.

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

2017-10-01

The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim

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.

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.

19 CFR 148.55 - Exemption for articles bearing American trademark.

Science.gov (United States)

2010-04-01

... registered with the U.S. Patent and Trademark Office and recorded with Customs. The exemption may be applied... 19 Customs Duties 2 2010-04-01 2010-04-01 false Exemption for articles bearing American trademark... § 148.55 Exemption for articles bearing American trademark. (a) Application of exemption. An exemption...

Design as a trademark

OpenAIRE

Oma, Turid

2016-01-01

How to obtain the most favourable protection for the shape of a product or its packaging: Similarities and differences between an EU registered three-dimensional trademark and a community registered design

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

lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide......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...... therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination...

Bortezomib: a novel therapy approved for multiple myeloma.

Science.gov (United States)

Richardson, Paul G; Anderson, Kenneth C

2003-10-01

Cellular homeostasis requires routine degradation of key regulatory proteins, including tumor suppressor gene products, transcription factors, cell-cycle proteins and their inhibitors, as well as damaged and misfolded proteins. A critical part of this process is mediated by the 26S proteasome, a multi-subunit enzyme found in the nucleus and cytoplasm of all eukaryotic cells. Because of its essential role in many cellular processes controlling growth and survival, the proteasome has been identified as a potential target for cancer therapy. Drugs known to inhibit proteasome activity have been shown to induce cell-cycle arrest and programmed cell death (apoptosis). The impact of this finding is heightened by research showing that cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB. Further preclinical evidence suggests that the antitumor effects of cytotoxic chemotherapy or radiotherapy may be enhanced by the addition of a proteasome inhibitor. Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.

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.

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.

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

Science.gov (United States)

Niesvizky, Ruben; Badros, Ashraf Z; Costa, Luciano J; Ely, Scott A; Singhal, Seema B; Stadtmauer, Edward A; Haideri, Nisreen A; Yacoub, Abdulraheem; Hess, Georg; Lentzsch, Suzanne; Spicka, Ivan; Chanan-Khan, Asher A; Raab, Marc S; Tarantolo, Stefano; Vij, Ravi; Zonder, Jeffrey A; Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Huang, Xin; Jiang, Yuqiu; Kim, Sindy T; Randolph, Sophia; Chen-Kiang, Selina

2015-01-01

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

The relevance of introducing opposition proceedings into the Serbian trademark legislation

OpenAIRE

Vasić Aleksandra

2014-01-01

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 groun...

Waste treatment by the CCP/EuRec {sup trademark} process; Abfallbehandlung nach dem CCP/EuRec {sup trademark} -Restabfallbehandlungsverfahren

Energy Technology Data Exchange (ETDEWEB)

Lippmann, A. [CCP GmbH, Waste Management, Merkers (Germany)

2002-07-01

The CCP/EuRec {sup trademark} process involves either an aerobic (composting) or an anaerobic (fermentation) biological treatment stage, or a combination of both. [German] Bei dem CCP/EuRec {sup trademark} -Restabfallbehandlungsverfahren handelt es sich um ein leistungsfaehiges System zur biologischen Behandlung von Restabfaellen. Die biologische Behandlungsstufe kann wahlweise aerob (Rotte) oder anaerob (Vergaerung) erfolgen. Eine Kombination zwischen beiden Varianten ist ebenfalls moeglich. (orig.)

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…

37 CFR 2.27 - Pending trademark application index; access to applications.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Pending trademark application... Registration § 2.27 Pending trademark application index; access to applications. (a) An index of pending... particular pending application will be permitted prior to publication under § 2.80 upon written request. (c...

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...

TRADEMARK VS BRAND: A CONCEPTUAL APPROACH

Directory of Open Access Journals (Sweden)

Tudor NISTORESCU

2013-06-01

Full Text Available In this paper we realized a study regarding the concepts of trademark and brand. There are numerous confusions between the two concepts, among theorists and practitioners. We deepened the debate related to these terms, studying a series of articles and papers in the field. Our research showed that there are differences of substance between the two concepts. If the trademark identifies a property right over an enterprise or a product, the brand is the sum of meanings and significations of a product, beyond the utility of that product or the service.

Evaluation of a hemostatic device with percutaneous collagen application (VasoSeal trademark) compared to a mechanical compression system (Compressar trademark -) after transfemoral catheterization of patients suffering from arterial occlusive disease

International Nuclear Information System (INIS)

Neudecker, A.; Lenhart, M.; Zorger, N.; Paetzel, C.; Feuerbach, S.; Link, J.; Manke, C.

2003-01-01

Purpose: Comparison of the efficacy of VasoSeal trademark and a mechanical compression system (Compressar trademark ) for percutaneous hemostasis after femoral arterial catheterization of patients with arterial occlusive disease. Materials and Methods: 60 patients underwent either diagnostic angiography or interventional procedures. The level of anticoagulation, blood pressure, and activation clotting time were recorded, and the time to hemostasis after sheath removal was measured. VasoSeal trademark application was considered ''successful'' if the compression time was less than two minutes. On the subsequent day as well as 4 months later, color coded Doppler ultrasound was performed to register treatment success and potential (late) complications. Results: 57 patients qualified for inclusion in this study. In 21 of the 26 patients who underwent the procedure with the VasoSeal trademark , immediate hemostasis was achieved within 1.75 minutes. In all 31 patients who had the Compressar trademark applied, hemostasis was successful with a mean compression time of 17.4 minutes. Thus, VasoSeal trademark significantly reduced hemostasis time irrespective of anticoagulation status, but it had a much higher incidence of minor local complications (bleeding, hematoma) compared to the control group (34.6% vs. 5.8%). The technical success was lower with VasoSeal trademark than with Compressar trademark (81% vs. 100%). Both groups had no severe or late complications. Conclusion: According to our results, VasoSeal trademark does not provide a suitable alternative compared to the effective, safe and cheap application of Compressar trademark as a hemostatic device. (orig.) [de

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.

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.

Science.gov (United States)

Siegel, David S; Dimopoulos, Meletios; Jagannath, Sundar; Goldschmidt, Hartmut; Durrant, Simon; Kaufman, Jonathan L; Leleu, Xavier; Nagler, Arnon; Offner, Fritz; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Gause, Christine; Vuocolo, Scott; Anderson, Kenneth C

2016-06-01

The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

2-gram-based Phonetic Feature Generation for Convolutional Neural Network in Assessment of Trademark Similarity

OpenAIRE

Ko, Kyung Pyo; Lee, Kwang Hee; Jang, Mi So; Park, Gun Hong

2018-01-01

A trademark is a mark used to identify various commodities. If same or similar trademark is registered for the same or similar commodity, the purchaser of the goods may be confused. Therefore, in the process of trademark registration examination, the examiner judges whether the trademark is the same or similar to the other applied or registered trademarks. The confusion in trademarks is based on the visual, phonetic or conceptual similarity of the marks. In this paper, we focus specifically o...

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.)

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.

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

International Nuclear Information System (INIS)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

2017-01-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH 2 dendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential. • Molecular simulation and thermodynamic

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

Energy Technology Data Exchange (ETDEWEB)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh, E-mail: umeshgupta175@gmail.com

2017-03-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH{sub 2}) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH{sub 2}). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH{sub 2} concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH{sub 2} dendrimers because it has more hydrophobic interior than G4-PAMAM-NH{sub 2} dendrimers. The release of BTZ from G5-PPI-NH{sub 2} complex was comparatively slower than G4-PAMAM-NH{sub 2}. The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential. �

Archveyor{trademark} automated mining system - implementation at the Conant mine

Energy Technology Data Exchange (ETDEWEB)

Hofmann, W.J. [Arch of Illinois, Percy, IL (United States)

1997-12-01

Arch Mineral Corporation, through the Arch Technology Department, has developed an automated continuous haulage mining system called the `Archveyor{trademark}`. The original technology came from a Russian patent. Kloeckner-Becorit (K-B) further developed the system and called it the `Mobile Conveyor`. This system was utilized in both coal and trona mines in the United States and Canada. Consolidation Coal designed their version of this continuous haulage system, called the `Tramveyor`. The Tramveyor is presently operating in their Dilworth Mine, in Pennsylvania. This system has no computer guidance system related to the continuous miner or the Tramveyor. Arch Mineral Corporation has further developed this continuous haulage mining system. Their system is a programmable, logic-controlled (PLC) automated mining system. A highwall version of the Archveyor{trademark} is being operated at Arch of Wyoming near Hanna, Wyoming. This paper introduces the first underground version of Archveyor{trademark} to be implemented at Conant Mine in southern Illinois. During the development process, the Archveyor{trademark} mining system consists of a continuous miner, a bolter car, the Archveyor{trademark} (itself), a stageloader, and an operator`s cab. During the secondary mining process the bolter car is taken out of the system.

Znaki towarowe w sporcie = Trademarks in sports

Directory of Open Access Journals (Sweden)

Krzysztof M. Westfal

2015-12-01

Abstract                     By getting the right protection for national trade mark, it is understood use of the mark for profit or for professional purposes throughout the territory of Poland. In contrast, a similar right conferred by a Community trade mark, concerns the application of the mark throughout the Community. Use of the mark is in particular the placement of the sign to the goods covered by the right of protection or their packaging, delivering and placing the goods on the market, import or export, as well as offering or providing services under that mark and the use of such a sign for advertising purposes. In the era of big money that undoubtedly govern the sport today, the law of trademarks, beside the rights to broadcast sporting events, gaining for all sporting significance of key organizational units. Clubs, associations and sports federations benefit from trademark rights, principally through the granting of licenses to entrepreneurs to use them. This process is most easily seen by the way the organization of major sporting events.                     As the aim of the research undersigned has chosen an indication of the legal rules governing trademarks in sports, in the face of ever increasing significance. The publication will include a presentation method and rules for the use of sports characters already registered by sports entities, as well as the benefits flowing from here. The implementation of the research will be carried out primarily by the method dogmatic. The analysis will be subject to national laws and EU. Taken the issue arises, however, need to take into account the achievements of other sciences, especially marketing, business and economics. Among the materials analyzed, in addition to the acts of commonly mention should also be stored in the data registers trademarks UP RP and OHIM. Behind the main conclusion flowing from this report should be regarded assertion that quality in modern

Advanced power conversion based on the Aerocapacitor{trademark}. Final report

Energy Technology Data Exchange (ETDEWEB)

Roark, D.

1997-03-05

This report summarizes work performed under contract No. DE-FC07-94ID13283, {open_quotes}Advanced Power Conversion Based on the Aerocapacitors{trademark}.{close_quotes} Under this contract high power density, high energy density, organic electrolyte Aerocapacitors{trademark} were developed and characterized for power conversion applications. Pilot facilities for manufacturing prototype AA-size Aerocapacitors{trademark} were put in place. The low ESR and good frequency response of these devices show that they are ideal components for high discharge rate and low to moderate frequency (< 10 kHz) applications such as power conversion.

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.

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

Photochemical Degradation of the Anticancer Drug Bortezomib by V-UV/UV (185/254 nm) Investigated by (1)H NMR Fingerprinting: A Way to Follow Aromaticity Evolution.

Science.gov (United States)

Martignac, Marion; Balayssac, Stéphane; Gilard, Véronique; Benoit-Marquié, Florence

2015-06-18

We have investigated the removal of bortezomib, an anticancer drug prescribed in multiple myeloma, using the photochemical advanced oxidation process of V-UV/UV (185/254 nm). We used two complementary analytical techniques to follow the removal rate of bortezomib. Nuclear magnetic resonance (NMR) is a nonselective method requiring no prior knowledge of the structures of the byproducts and permits us to provide a spectral signature (fingerprinting approach). This untargeted method provides clues to the molecular structure changes and information on the degradation of the parent drug during the irradiation process. This holistic NMR approach could provide information for monitoring aromaticity evolution. We use liquid chromatography, coupled with high-resolution mass spectrometry (LC-MS), to correlate results obtained by (1)H NMR and for accurate identification of the byproducts, in order to understand the mechanistic degradation pathways of bortezomib. The results show that primary byproducts come from photoassisted deboronation of bortezomib at 254 nm. A secondary byproduct of pyrazinecarboxamide was also identified. We obtained a reliable correlation between these two analytical techniques.

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.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial

DEFF Research Database (Denmark)

Gimsing, P; Hjertner, Ø; Abildgaard, N

2015-01-01

, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared......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...... included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT...

CHROMAT trademark Version 1.1--Soil Chromium Attenuation Evaluation Model

International Nuclear Information System (INIS)

Felmy, A.R.; Rai, D.; Zachara, J.M.; Thapa, M.; Gold, M.

1992-07-01

This document is the user's manual and technical reference for the Soil Chromium Attenuation Model (CHROMAT trademark), a computer code designed to calculate both the dissolved Cr concentration and the amount of Cr attenuated in soils as a result of the geochemical reactions that occur as Cr-containing leachates migrate through porous soils. The dissolved Cr concentration and the amount of Cr attenuated are calculated using thermodynamic (mechanistic) data for aqueous complexation reactions, adsorption/ desorption reactions, and precipitation/dissolution reactions involving both CR(III) and Cr(VI) species. Use of this mechanistic approach means that CHROMAT trademark requires a minimum amount of site-specific data on leachate and soil characteristics. CHROMAT trademark is distributed in executable form for IBM and IBM-compatible personal computers through a license from the Electric Power Research Institute (EPRI). The user interacts with CHROMAT trademark using menu-driven screen displays. Interactive on-line help options are available. Output from the code can be obtained in tabular or graphic form. This manual describes the development of CHROMAT trademark, including experimental data development in support of the model and model validation studies. The thermodynamic data and computational algorithm are also described. Example problems and results are included

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

Praktik Trademark Squatting dalam Proses Pendaftaran Merek di Indonesia

OpenAIRE

Widya Justitia

2016-01-01

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...

Clinical implications of a new TSH-receptor-antibody-assay (DYNOtest {sup trademark} TRAKhuman) in autoimmune thyroid diseases; Klinische Implikationen eines neuen TSH-Rezeptor-Antikoerper-Assays (DYNOtest {sup trademark} TRAKhuman) bei autoimmunen Schilddruesenerkrankungen

Energy Technology Data Exchange (ETDEWEB)

Meller, J.; Schreivogel, I.; Becker, W. [Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin; Bergmann, A.; Morgenthaler, N. [B.R.A.H.M.S Diagnostica, Berlin (Germany); Huefner, M. [Goettingen Univ. (Germany). Abt. Innere Medizin

2000-07-01

Aim: Conventional radioreceptor-antibody-assays (RAAs) fail in the detection of TSH-receptor antibodies (TRAKs) in 10-30% of patients with Graves' disease (GD). The aim of this study was the evaluation of the diagnostic and clinical impact of a new RRA (DYNOtest {sup trademark} TRAKhuman) which uses the human recombinant TSH-Receptor in the diagnosis of autoimmune thyroid disease. Methods: Sera from 142 consecutive patients (GD: n=50, autoimmune thyroiditis/AIT: n=92) and from 55 controls (31 patients without any thyroid disease and 14 with euthyroid goiter) were evaluated both with the DYNOtest {sup trademark} TRAKhuman-assay and a conventional RRA (TRAK-Assay {sup trademark}). Thyroid in vitro parameters and thyroid sonography were performed in all patients. Results: The DYNOtest {sup trademark} TRAK-assay was significantly superior to the conventional RRA in the diagnosis of GD (p<0,00012), especially in those who were treated by thionamides (p<0,003) and in the diagnosis of TRAK-positive patients with AIT (p<0,003). The majority of TRAK-positive AIT-patients suffered from hypothyroidism. One false positive result in patients with euthyroid goiter was found in the TRAK-Assay {sup trademark} as well as in the DYNOtest {sup trademark} TRAKhuman-Assay. Therefore the specifity of the DYNOtest {sup trademark} TRAKhuman was not inferior compared with the conventional assay. Conclusion: The DYNOtest {sup trademark} TRAK-assay is superior in the diagnostic work up of Graves' disease compared with a conventional TRAK-assay and offers an equal specifity. (orig.) [German] Ziel: Bei konventionellen Radiorezeptor-Antikoerper-Assays (RRAs) misslingt der Nachweis von TSH-Rezeptor Antikoerpern (TRAKS) bei 10-30% der immunogenen Hyperthyreosen (IH). Ziel der Studie war es, den diagnostischen und klinischen Stellenwertes eines neuen RRA (DYNOtest {sup trademark} TRAKhuman) bei autoimmunen Schilddruesenerkrankungen zu evaluieren. Methoden: Serumproben von 142

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

Science.gov (United States)

Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-02-01

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

19 CFR 134.47 - Souvenirs and articles marked with trademarks or trade names.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Souvenirs and articles marked with trademarks or... Imported Articles § 134.47 Souvenirs and articles marked with trademarks or trade names. When as part of a trademark or trade name or as part of a souvenir marking, the name of a location in the United States or...

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-six e...

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.

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.

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.

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.

Bioglass {sup trademark} coated poly(DL-lactide) foams for tissue engineering scaffolds

Energy Technology Data Exchange (ETDEWEB)

Gough, J.E. [Materials Science Centre, UMIST, Manchester M1 7HS (United Kingdom); Arumugam, M. [Department of Materials Science and Metallurgy, University of Cambridge, Cambridge (United Kingdom); Blaker, J. [Department of Materials and Centre for Tissue Engineering and Regenerative Medicine, Imperial College London, London SW7 2BP (United Kingdom); Boccaccini, A.R. [Dept. of Materials and Center for Tissue Engineering and Regenerative Medicine, Imperial College London, London SW7 28P (United Kingdom)

2003-07-01

The purpose of this study was to prepare poly(DL-lactic acid) (PDLLA)/Bioglass trademark composites of foam-like structure, to measure the degree of bioactivity of the composites by studying the formation of hydroxyapatite (HA) after immersion in simulated body fluid (SBF) and to test the initial attachment of human osteoblasts within the porous network. It was found that crystalline HA formed on the Bioglass trademark coated PDLLA foams after 7 days of immersion in SBF. HA formed also on the surfaces of non-coated PDLLA foams, however the rate and amount of HA formation were much lower than in the composites. The rapid formation of HA on the Bioglass trademark /PDLLA foam surfaces confirmed the high bioactivity of these materials. Osteoblasts attached within the porous network throughout the depth of the foams. Cell density was found to be higher in the PDLLA/Bioglass trademark composites compared to the pure PDLLA foams. The composite foams developed here exhibit the required bioactivity to be used as scaffolds for bone tissue engineering. (Abstract Copyright [2003], Wiley Periodicals, Inc.) [German] Die vorliegende Arbeit befasst sich mit der Herstellung von poroesen Verbundwerkstoffen bestehend aus Poly(DL-Laktidsaeure) (PDLLA) und Bioglass trademark und der anschliessenden Untersuchung der Bioaktivitaet. Die Bioaktivitaet wurde anhand von In-vitro-Methoden untersucht: Durch Ermittlung der Bildungsrate von Hydroxylapatit (HA) auf der Oberflaeche nach Eintauchen in simulierter Koerperfluessigkeit (SBF) und mittels Zellkulturstudien mit menschlichen Osteoblasten. Nach 7 Tagen in SBF hatte die Bildung von kristallinem HA auf der Oberflaeche von mit Bioglass trademark -beschichteten PDLLA Schaeumen stattgefunden. Auf der Oberflaeche von unbeschichtetem PDLLA konnte ebenfalls die Bildung von HA gezeigt werden, jedoch war die Bildungsrate hier bedeutend langsamer verglichen mit den Verbundwerkstoffen. Die rasche Formung von HA auf der Bioglass trademark /PDLLA

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

International Nuclear Information System (INIS)

Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

2010-01-01

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. 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. 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. 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

76 FR 11208 - Proposed Collection; Substantive Submissions Made During Prosecution of the Trademark Application

Science.gov (United States)

2011-03-01

... Petition to Revive Deficiency Letter, Petition to the Director Under Trademark Rule 2.146, Due Diligence...) Due Diligence Petition Under Trademark Rule 2.66 (Paper).. 20 7 2 Due Diligence Petition Under... 0.44 2.00 Petition to the Director Under Trademark Rule 2.146....... 16 0.44 7.00 Due Diligence...

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.

ULTOR(Registered TradeMark) Passive Pose and Position Engine For Spacecraft Relative Navigation

Science.gov (United States)

Hannah, S. Joel

2008-01-01

The ULTOR(Registered TradeMark) Passive Pose and Position Engine (P3E) technology, developed by Advanced Optical Systems, Inc (AOS), uses real-time image correlation to provide relative position and pose data for spacecraft guidance, navigation, and control. Potential data sources include a wide variety of sensors, including visible and infrared cameras. ULTOR(Registered TradeMark) P3E has been demonstrated on a number of host processing platforms. NASA is integrating ULTOR(Registerd TradeMark) P3E into its Relative Navigation System (RNS), which is being developed for the upcoming Hubble Space Telescope (HST) Servicing Mission 4 (SM4). During SM4 ULTOR(Registered TradeMark) P3E will perform realtime pose and position measurements during both the approach and departure phases of the mission. This paper describes the RNS implementation of ULTOR(Registered TradeMark) P3E, and presents results from NASA's hardware-in-the-loop simulation testing against the HST mockup.

Operational experience for the latest generation of ATRIUM trademark 10 fuel assemblies

International Nuclear Information System (INIS)

Schoss, Volker; Hoffmann, Petra Britt; Schaefer, Jens

2011-01-01

AREVA NP's ATRIUM trademark 10 product family was first introduced to the BWR market in 1992. Lead test campaigns confirmed the outstanding product performance and justified introduction of reload quantities. Further development of particular product features was demonstrated and implemented in the fuel design to meet highest expectations for reliability and fuel economics. The latest generation called ATRIUM trademark 10XP and subsequently ATRIUM trademark 10XM was introduced in 2002 and 2005, respectively. The first lead test assemblies completed their operation successfully after seven cycles. (orig.)

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

Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

Directory of Open Access Journals (Sweden)

Chim Chor

2012-06-01

Full Text Available Abstract Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone before autologous stem cell transplantation (ASCT. Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone or VTD (bortezomib/thalidomide/dexamethasone induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25, PAD (N = 31, VTD (N = 35]. and received thalidomide maintenance for 2 years post-ASCT. Results 43 (47.3% patients had International Staging System (ISS III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS and event-free (EFS survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

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

77 FR 49426 - Notice of Inquiry Regarding Adjustment of Fees for Trademark Applications

Science.gov (United States)

2012-08-16

... Trademark Assistance Center, Concourse Level, James Madison Building-East Wing, 600 Dulany Street... , and will also be available at the Office of the Commissioner for Trademarks, Madison East, Tenth Floor...

Convolutional Neural Network on Embedded Linux(trademark) System-on-Chip: A Methodology and Performance Benchmark

Science.gov (United States)

2016-05-01

Linux® is a registered trademark of Linus Torvalds. NVIDIA ® is a registered trademark of NVIDIA Corporation. Oracle® is a registered trademark of...two NVIDIA ® GTX580 GPUs [3]. Therefore, for this initial work, we decided to concentrate on small networks and small datasets until the methods are

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.

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.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

International Nuclear Information System (INIS)

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell; Mallon, Gayle; Myers, Thomas; Ramirez, Michael; Andrews, David; Curran, Walter J.; Dicker, Adam P.

2009-01-01

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m 2 /dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m 2 starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m 2 /dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m 2 ) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.

37 CFR 2.190 - Addresses for trademark correspondence with the United States Patent and Trademark Office.

Science.gov (United States)

2010-07-01

... filed through the Office's web site, at http://www.uspto.gov. Paper documents and cover sheets to be... trademark documents can be ordered through the Office's web site at www.uspto.gov. Paper requests for...: Madrid Processing Unit, 600 Dulany Street, MDE-7B87, Alexandria, VA 22314-5793. [68 FR 48289, Aug. 13...

37 CFR 1.414 - The United States Patent and Trademark Office as a Designated Office or Elected Office.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false The United States Patent and Trademark Office as a Designated Office or Elected Office. 1.414 Section 1.414 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES International Processing...

Legal Protection of Well-known Trademark Rights in China : History, Current Situation and Challenge

OpenAIRE

Chen, Zhu

2010-01-01

The legal term of “Well-Known Trademark” first appeared in the 1883 Paris Convention for the Protection of Industrial Property, which sets forth the principles for granting special protection to well-known trademarks. In recent years, Sino-US disputes over intellectual property protection have the trend to upgrade, and among these disputes, well-known trademark protection is an important cornerstone. In recent years in China, the well-known trademark protection system is still relatively week...

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.

Competition in prescription drug markets: the roles of trademarks, advertising, and generic names.

Science.gov (United States)

Feldman, Roger; Lobo, Félix

2013-08-01

We take on two subjects of controversy among economists-advertising and trademarks-in the context of the market for generic drugs. We outline a model in which trademarks for drug names reduce search costs but increase product differentiation. In this particular framework, trademarks may not benefit consumers. In contrast, the generic names of drugs or "International Nonproprietary Names" (INN) have unquestionable benefits in both economic theory and empirical studies. We offer a second model where advertising of a brand-name drug creates recognition for the generic name. The monopoly patent-holder advertises less than in the absence of a competitive spillover.

16 CFR 303.41 - Use of fiber trademarks and generic names in advertising.

Science.gov (United States)

2010-01-01

... use of a fiber trademark shall require a full disclosure of the fiber content information required by... or generic name is used in non-required information in advertising, such fiber trademark or generic... advertising. 303.41 Section 303.41 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC...

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

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.

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

International Nuclear Information System (INIS)

Thompson, B.; Slifko, A.

1998-01-01

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

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.

Analysis of two commercially available bortezomib products: differences in assay of active agent and impurity profile.

Science.gov (United States)

Byrn, Stephen R; Tishmack, Patrick A; Milton, Mark J; van de Velde, Helgi

2011-06-01

The analytical properties of two commercially available bortezomib products (VELCADE(®) and Bortenat) were compared using nuclear magnetic resonance, mass spectrometry, high-performance liquid chromatography, and gas chromatography. The data showed differences between the two products. Based on these data, Bortenat samples contained more active ingredients than indicated by the label (mean, 116.5% and 117.9% of label, in 2-mg and 3.5-mg vials, respectively). In comparison, VELCADE samples contained a mean of 99.3% of active ingredient, which was consistent with the approved specification range (US, 90-110%; EU, 95-105%). Clinical data demonstrate that patients exposed to higher than recommended doses of bortezomib on the standard twice-weekly dosing schedule are likely to have an increased risk of major toxicities. Bortenat 2-mg vials contained an isovaleraldehyde impurity; the origin of this is unknown. Additionally, the ratio of boronic acid to boronic ester differed between Bortenat 2 mg (0.27:1) and 3.5 mg (0.13:1) and VELCADE (0.10:1) samples reconstituted in saline indicating that the Bortenat product is not equivalent to the VELCADE product.

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 ...

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

DEFF Research Database (Denmark)

Schovsbo, Jens Hemmingsen

2017-01-01

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......This paper analyses the new provisions in EU law that trademark rules should be “applied in a way that ensures full respect for fundamental rights and freedoms, and in particular the freedom of expression”. It is pointed out how these provisions are part of a broader trend....... 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...

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

Science.gov (United States)

García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

2017-12-01

Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Sub-criticality monitoring for ADTR trademark control

International Nuclear Information System (INIS)

Ashworth, Roger

2014-01-01

Following the debut of the Accelerator Driven Thorium Reactor (ADTR trademark) Power Station at ENC 2010 in Barcelona, thorium as a reactor fuel has gained increasing support. The ADTR trademark concept reactor introduced the combination of an accelerator driven system (ADS) with traditional control rod technology, to provide a very high gain novel sub-critical ADS reactor design. The high gain of the system, while significantly reducing the demands on the accelerator design, pushes up operational sub-criticality (k eff ) closer to unity. In this paper we review this design and the progress made since ENC 2010. We compare 2 different methods of measuring the sub-critical neutron multiplication factor as the fuel cycle develops. The paper discusses the most recent work on k eff measurement and the interesting relationship between neutron flux, accelerator current and fuel temperature when using beam pulse methods to determine operational sub-criticality, of which a European patent is being granted. (orig.)

External Data and Attribute Hyperlink Programs for Promis*e(Registered Trademark)

Science.gov (United States)

Derengowski, Rich; Gruel, Andrew

2001-01-01

External Data and Attribute Hyperlink are computer programs that can be added to Promis*e(trademark) which is a commercial software system that automates routine tasks in the design (including drawing schematic diagrams) of electrical control systems. The programs were developed under the Stennis Space Center's (SSC) Dual Use Technology Development Program to provide capabilities for SSC's BMCS configuration management system which uses Promis*e(trademark). The External Data program enables the storage and management of information in an external database linked to a drawing. Changes can be made either in the database or on the drawing. Information that originates outside Promis*e(trademark) can be stored in custom fields that can be added to the database. Although this information is not available in Promis*e(trademark) printed drawings, it can be associated with symbols in the drawings, and can be retrieved through the drawings when the software is running. The Attribute Hyperlink program enables the addition of hyperlink information as attributes of symbols. This program enables the formation of a direct hyperlink between a schematic diagram and an Internet site or a file on a compact disk, on the user's hard drive, or on another computer on a network to which the user's computer is connected. The user can then obtain information directly related to the part (e.g., maintenance, or troubleshooting information) associated with the hyperlink.

Oxygen Plasma Modification of Poss-Coated Kapton(Registered TradeMark) HN Films

Science.gov (United States)

Wohl, C. J.; Belcher, M. A.; Ghose, S.; Connell, J. W.

2008-01-01

The surface energy of a material depends on both surface composition and topographic features. In an effort to modify the surface topography of Kapton(Registered TradeMark) HN film, organic solutions of a polyhedral oligomeric silsesquioxane, octakis(dimethylsilyloxy)silsesquioxane (POSS), were spray-coated onto the Kapton(Registered TradeMark) HN surface. Prior to POSS application, the Kapton(Registered TradeMark) HN film was activated by exposure to radio frequency (RF)-generated oxygen plasma. After POSS deposition and solvent evaporation, the films were exposed to various durations of RF-generated oxygen plasma to create a topographically rich surface. The modified films were characterized using optical microscopy, attenuated total reflection infrared (ATR-IR) spectroscopy, and high-resolution scanning electron microscopy (HRSEM). The physical properties of the modified films will be presented.

Development of Collective Trademark for Batik Industry in Kampung Batik Laweyan (Laweyan Batik’s Village, Solo

Directory of Open Access Journals (Sweden)

Agus Sardjono

2015-04-01

Full Text Available In the previous research, it was found that the individual trademark system has not been effectively utilized to support the business of batik SMEs, particularly in several Batik industry centers in Java, namely Bantul in Yogyakarta province, Kauman in Pekalongan, and Laweyan in Solo. However, the fact that those SMEs gather in a community, organization, or kinships bring potentials for development of collective trademarks, which can address the problems that individual trademark cannot anticipate. This can also be a strategy to anticipate the free-trade ‘attack,’ i.e. imported textiles with batik patterns/motifs; yet not the original Indonesian Batik. Therefore, Indonesian batik SMEs need to be nurtured and encouraged to register their own collective trademarks, and to build their branding infrastructure, through local batik community’s standardization, and collective batik labeling. This present research focuses on the development of collective trademark utilization by one long-known Batik community in Solo province, Kampung Batik Laweyan.

The inner containment of an EPR trademark pressurized water reactor

Energy Technology Data Exchange (ETDEWEB)

Ostermann, Dirk; Krumb, Christian; Wienand, Burkhard [AREVA GmbH, Offenbach (Germany)

2014-08-15

On February 12, 2014 the containment pressure and subsequent leak tightness tests on the containment of the Finnish Olkiluoto 3 EPR trademark reactor building were completed successfully. The containment of an EPR trademark pressurized water reactor consists of an outer containment to protect the reactor building against external hazards (such as airplane crash) and of an inner containment that is subjected to internal overpressure and high temperature in case of internal accidents. The current paper gives an overview of the containment structure, the design criteria, the validation by analyses and experiments and the containment pressure test.

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

... to the USPTO's past practice of indefinitely retaining papers that have been scanned into TICRS stems... One-Year Retention Period for Trademark- Related Papers That Have Been Scanned Into the Trademark... retention period that began on September 26, 2011, for papers scanned into the Trademark Initial Capture...

BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-κB.

Science.gov (United States)

Rushworth, Stuart A; Bowles, Kristian M; Barrera, Lawrence N; Murray, Megan Y; Zaitseva, Lyubov; MacEwan, David J

2013-01-01

Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical activity in chronic lymphocytic leukaemia (CLL) effecting cell death through inhibition of Bruton's tyrosine kinase (BTK). In this study we report for the first time that ibrutinib is cytotoxic to malignant plasma cells from patients with multiple myeloma (MM) and furthermore that treatment with ibrutinib significantly augments the cytotoxic activity of bortezomib and lenalidomide chemotherapies. We describe that the cytotoxicity of ibrutinib in MM is mediated via an inhibitory effect on the nuclear factor-κB (NF-κB) pathway. Specifically, ibrutinib blocks the phosphorylation of serine-536 of the p65 subunit of NF-κB, preventing its nuclear translocation, resulting in down-regulation of anti-apoptotic proteins Bcl-xL, FLIP(L) and survivin and culminating in caspase-mediated apoptosis within the malignant plasma cells. Taken together these data provide a platform for clinical trials of ibrutinib in myeloma and a rationale for its use in combination therapy, particularly with bortezomib. Copyright © 2012 Elsevier Inc. All rights reserved.

Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

Science.gov (United States)

Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

2015-09-01

There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8 + T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

Fuel and power coproduction: The Liquid Phase Methanol (LPMEOH{trademark}) process demonstration at Kingsport

Energy Technology Data Exchange (ETDEWEB)

Drown, D.P.; Brown, W.R.; Heydorn, E.C.; Moore, R.B.; Schaub, E.S.; Brown, D.M.; Jones, W.C.; Kornosky, R.M.

1997-12-31

The Liquid Phase Methanol (LPMEOH{trademark}) process uses a slurry bubble column reactor to convert syngas (primarily a mixture of carbon monoxide and hydrogen) to methanol. Because of its superior heat management, the process is able to be designed to directly handle the carbon monoxide (CO)-rich syngas characteristic of the gasification of coal, petroleum coke, residual oil, wastes, or of other hydrocarbon feedstocks. When added to an integrated gasification combined cycle (IGCC) power plant, the LPMEOH{trademark} process converts a portion of the CO-rich syngas produced by the gasifier to methanol, and the remainder of the unconverted gas is used to fuel the gas turbine combined-cycle power plant. The LPMEOH{trademark} process has the flexibility to operate in a daily electricity demand load-following manner. Coproduction of power and methanol via IGCC and the LPMEOH{trademark} process provides opportunities for energy storage for electrical demand peak shaving, clean fuel for export, and/or chemical methanol sales.

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

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.

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...

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.

Analysis of Two Commercially Available Bortezomib Products: Differences in Assay of Active Agent and Impurity Profile

OpenAIRE

Byrn, Stephen R.; Tishmack, Patrick A.; Milton, Mark J.; van de Velde, Helgi

2011-01-01

The analytical properties of two commercially available bortezomib products (VELCADE® and Bortenat) were compared using nuclear magnetic resonance, mass spectrometry, high-performance liquid chromatography, and gas chromatography. The data showed differences between the two products. Based on these data, Bortenat samples contained more active ingredients than indicated by the label (mean, 116.5% and 117.9% of label, in 2-mg and 3.5-mg vials, respectively). In comparison, VELCADE samples conta...

Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations.

Science.gov (United States)

Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

2017-03-01

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH10.0, respectively (pdendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Affect of Bioglass {sup trademark} repeat dosage on mineralisation of embryonic bone 'in vitro'

Energy Technology Data Exchange (ETDEWEB)

Maroothynaden, J. [Imperial Coll. of Medicine, London (United Kingdom). Microgravity Tissue Engineering Lab.; Hench, L.L. [Imperial Coll. of Science, Technology and Medicine, London (United Kingdom). Dept. of Materials

2001-07-01

Utilising 45S5 Bioglass {sup trademark} extracts, as described previously, 16-day gestation embryonic mouse long-bones were cultured for 4-days while exposed to the same Bioglass{sup circledR} soluble extract solution for two different exposure times. In the first culture, all embryonic femurs were exposed to fresh 45S5 Bioglass {sup trademark} extract every 98 hours. In the second, the long-bones were exposed to fresh 45S5 Bioglass {sup trademark} extract solution every 48 hours. A simultaneous control culture was performed. All embryonic long-bone cultures mineralised after 4-days culture. Increasing the frequency of 45S5 Bioglass {sup trademark} exposure, from one exposure every 96 hrs to fresh exposures every 48 hrs, significantly increased the length and mineral content of the embryonic long-bones. (orig.)

The AMTEX Partnership{trademark}. Fourth quarter FY95 report

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

The AMTEX Partnership{trademark} is a collaborative research and development program among the US Integrated Textile Industry, the Department of Energy (DOE), the national 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 operations and program management of the AMTEX Partnership{trademark} 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. Progress is reported on the following projects: computer-aided fabric evaluation; cotton biotechnology; demand activated manufacturing architecture; electronic embedded fingerprints; on-line process control for flexible fiber manufacturing; rapid cutting; sensors for agile manufacturing; and textile resource conservation.

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)

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

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

76 FR 34062 - Patent and Trademark Financial Transactions

Science.gov (United States)

2011-06-10

... processing and other services related to patents, trademarks, and information products. Customers may submit... EFT to make online fee payments to the USPTO. Customers must first establish a user profile with their... financial activity records online, customers may create a Financial Profile through the USPTO Web site...

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...

77 FR 58097 - Extension of Comment Period for Notice of Inquiry Regarding Adjustment of Fees for Trademark...

Science.gov (United States)

2012-09-19

... Trademark Assistance Center, Concourse Level, James Madison Building-East Wing, 600 Dulany Street... , and will also be available at the Office of the Commissioner for Trademarks, Madison East, Tenth Floor...

PROTECTION OF WORKS TITLES FROM THE PERSPECTIVE OF COPYRIGHT PROTECTION AND TRADEMARK PROTECTION

Directory of Open Access Journals (Sweden)

George-Mihai IRIMESCU

2017-05-01

Full Text Available The main purpose of the paper is assessing the possibilities of protecting the titles of works. One possibility is the protection by means of registered or unregistered trademarks. This route presents difficulties because of the distinctiveness perspective. In this sense, the European case-law has recently developed a constant practice and outlined a series of criteria that should be taken into consideration when examining a trademark consisting of a title. Another possibility is protecting the title under the provisions of the copyright law. From this respect, the practice has not yet determined a constant practice. However, the dominant opinion is that the originality criterion should be taken into consideration when assessing the protection of a tile. Finally, brief conclusion are made, including short remarks on the cumulative protection of titles, both as trademarks and under the copyright law.

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

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

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

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

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 ...

Nexsys{trademark} real time risk management system and demonstration at Kushiro coal mine

Energy Technology Data Exchange (ETDEWEB)

Addinell, S.J.; Rowan, G.; Matsuyama, S. [CSIRO (Australia). Division of Exploration and Mining

2005-03-01

In March 2005, the CSIRO Nexsys{trademark} development team travelled to Kushiro Coal Mine (KCM) to install and evaluate the Nexsys{trademark} real time risk management system developed under joint collaboration with JCOAL and other industry partners. After successful installation and configuration the system was able to interface directly to the existing mine site MELSEC monitoring hardware and system database. Once fully commissioned, Nexsys{trademark} will provide mine operators with a real-time risk management system with the capability to initiate preemptive Trigger Action Response Plans (TARPS) should mine operating parameters change for the worse. A range of autonomous altering and alarming options are available, including the capability to email the nature and severity of the alarm to key personnel, on or off site. The system is also fully compatible with wireless network systems and can be accessed through WLAN devices such as Ethernet enabled PDAs. 2 refs., 3 figs.

ASRC Aerospace Corporation Selects Dynamically Reconfigurable Anadigm(Registered Trademark) FPAA For Advanced Data Acquisition System

Science.gov (United States)

Mata, Carlos T.

2003-01-01

Anadigm(registered trademark) today announced that ASRC Aerospace Corporation has designed Anadigm's dynamically reconfigurable Field Programmable Analog Array (FPAA) technology into an advanced data acquisition system developed under contract for NASA. ASRC Aerospace designed in the Anadigm(registered trademark) FPAA to provide complex analog signal conditioning in its intelligent, self-calibrating, and self-healing advanced data acquisition system (ADAS). The ADAS has potential applications in industrial, manufacturing, and aerospace markets. This system offers highly reliable operation while reducing the need for user interaction. Anadigm(registered trademark)'s dynamically reconfigurable FPAAs can be reconfigured in-system by the designer or on the fly by a microprocessor. A single device can thus be programmed to implement multiple analog functions and/or to adapt on-the-fly to maintain precision operation despite system degradation and aging. In the case of the ASRC advanced data acquisition system, the FPAA helps ensure that the system will continue to operating at 100% functionality despite changes in the environment, component degradation, and/or component failures.

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

... Cynthia C. Lynch; by hand delivery to the Trademark Assistance Center, Concourse Level, James Madison... Commissioner for Trademarks, Madison East, Tenth Floor, 600 Dulany Street, Alexandria, Virginia. Because...

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.

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 11 discusses Radiation Protection, Conduct of Operations, and the Initial Test Program

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

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

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

Science.gov (United States)

2010-01-01

..., trademarks or graphic representations prohibited. 301.43 Section 301.43 Commercial Practices FEDERAL TRADE... 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...

Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials.

Science.gov (United States)

Mateos, Maria-Victoria; Oriol, Albert; Martínez-López, Joaquín; Teruel, Ana-Isabel; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Esseltine, Dixie-Lee; Cakana, Andrew; Pei, Lixia; van de Velde, Helgi; Miguel, Jesus San

2016-12-01

Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m 2 ); median dose intensity was lower (2.0 vs 5.1 mg/m 2 /month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen. NCT00111319, NCT00443235.

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

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.

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).

Registered Trademarks… Reflections on the use of trademarks, consumption patterns and marketing strategies in rural areas of Argentina (1900-1930

Directory of Open Access Journals (Sweden)

Andrea Lluch

2013-06-01

Full Text Available Trademarks are highly valuable devices that serve a relevant purpose in trade and consumption patterns. However, trademarks have been largely neglected by Argentina's economic history historiography. This article discusses how and when trademarks emerged and spread in Argentina's rural area in the early 20th century. It describes this gradual process, pointing out that, by the late 1920s, trademarks had already become a prominent feature in rural marketing strategies and consumption patterns. The study also analyzes how these processes contributed to shaping retailers' business practices as well as generic consumer goods' marketing channels (particularly, in the food and beverage industries

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.

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

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.

Trademarks enhance customers' trust; Die Marke schafft Vertrauen

Energy Technology Data Exchange (ETDEWEB)

Forst, M.

2007-07-01

While users still rely primarily on the product features of solar systems, the importance of trademarks is increasing, and it is to be expected that sales in future will be determined not only by availability but also by image. The solar industry is fighting for the image of its products. (orig.)

Implementation of a Semantic Network Service (SNS) in the context of the German Environmental Information Network (gein trademark). Vol. 1 and 2; Erstellung eines semantischen Netzwerkservice (SNS) fuer das Umweltinformationsnetz Deutschland - German Environmental Information Network (gein trademark). Bd. 1 und 2

Energy Technology Data Exchange (ETDEWEB)

Bandholtz, T.

2003-05-01

Encouraged by the success of the thesaurus-based automatic indexing of environmental information provided by the German Environmental Information Network (gein {sup trademark}, http://www.gein.de), the terminology collections of gein {sup trademark} have been integrated and cross-networked in a comprehensive Topic Map. On this base, the text analysis module could be considerably enhanced. Any access to the terminology and its methods has been provided by means of Web Services. gein {sup trademark} (starting with version 2003) incorporates these Web Services in the productive installation. Besides that, SNS provides basic functionality for terminology editors. (orig.)

Hubble Space Telescope Metallized Teflon(registered trademark) FEP Thermal Control Materials: On-Orbit Degradation and Post-Retrieval Analysis

Science.gov (United States)

Townsend, Jacqueline A.; Hansen, Patricia A.; Dever, J. A.; deGroh, K. K.; Banks, B.; Wang, L.; He, C.

1988-01-01

During the Hubble Space Telescope (HST) Second Servicing Mission (SM2), degradation of unsupported Teflon(Registered Trademark) FEP (fluorinated ethylene propylene), used as the outer layer of the multilayer insulation (MLI) blankets, was evident as large cracks on the telescope light shield. A sample of the degraded outer layer was retrieved during the mission and returned to Earth for ground testing and evaluation. The results of the Teflon(Registered Trademark) FEP sample evaluation and additional testing of pristine Teflon(Registered Trademark) FEP led the investigative team to theorize that the HST damage was caused by thermal cycling with deep-layer damage from electron and proton radiation which allowed the propagation of cracks along stress concentrations , and that the damage increased with the combined total dose of electrons, protons, UV and x-rays along with thermal cycling. This paper discusses the testing and evaluation of the retrieved Teflon(Registered Trademark) FEP.

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...

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...

76 FR 82279 - Electronic Delivery of Search Results From the United States Patent and Trademark Office to the...

Science.gov (United States)

2011-12-30

...] Electronic Delivery of Search Results From the United States Patent and Trademark Office to the European... United States Patent and Trademark Office (USPTO) has recently begun electronic delivery of search... the search results from a previously filed patent application to which the European patent application...

TRADEMARK APPLICATIONS IN A SECTORAL APPROACH

Directory of Open Access Journals (Sweden)

MATE Domician

2015-07-01

Full Text Available The economic roles of the Intellectual Property Rights (IPRs are one of the key mysteries of the economic theories. At the beginning of the 1760s a sustained and rapid growth in per capita income occurred all over the word and since then the broad history of economic institutions has still quite important. This research paper relies on the conceptual framework of IPRs. However, the academic literature has claimed that the presences of these institutions are essential elements of a well-functioning economy, but intellectual property has come to mean not only the right to own and sell, but also the right to regulate its use. Moreover several unexploited dilemmas have still remained in practice. In order to support the theoretical insights we inspect to overview the trademarks growth tendencies in various OECD countries. In this perspective we followed a specific taxonomy of the traditional Nice Classes (NCL to identify the distribution and the growth changes of these property right applications in a specific sectoral approach. Besides determining the differences with some comparative statistics in the branches, we could also demonstrate the economic importance of trademark applicants that place on the protection of brands in the service-oriented industries. However, there was falls in due to the last economic crisis; it seemed to follow a persistent and substantial growth path again. In this sense, we could also suggest the better valorization of IPRs that must be considered in a context to facilitate SMEs’ access to the benefits of globalised markets in these industries.

商標名稱通用化之理論與實務 The Theories and Practices of Trademark

Directory of Open Access Journals (Sweden)

鄧振球 Cheng-Chiou Teng

2008-06-01

Full Text Available 商標具有表彰商品來源之功能，商標之設計為順應其功能，必須具有識別性，不具識別性之商標設計，不僅無法註冊，更無法主張商標專用之權利。商標名稱通用化，則是指原本具有識別性之商標，通常為著名商標，因為社會大眾消費習慣以及認知的改變，變成商品的通用名稱，落入公共財領域，無法受到法律之保護。商標名稱通用化，在國外並非新概念，惟在我國商標法領域中因屬新規定，未見我國學者進行專門之闡述。本文乃參考美國法制，就商標名稱通用化之意義、形成原因、判斷標準、法律效果，以及我國法制之檢討等議題，分別加以闡釋，期有助於解決商標名稱通用化所衍生 之各項行政救濟，以及法院訴訟上面臨之新議題。 A basic function of trademarks is to identify the source of a product. In order to carry out this function, it is necessary to design a trademark with distinctiveness. A trademark without distinctiveness can not be registered with the Patent and Trademark Office or serve as a basis for claiming trademark rights because it lacks the function of source identification. Trademark genericism, also known as genericide, genericness and generalization, is the rule which governs the loss of trademark protection of a registered trademark that was once distinctive and often well known, but fell into the public domain and became a generic name owing to the change in the perception of the consuming public. Genericism in U.S. court practices is not a new concept but is just beginning to appear in Taiwanese Trademark Law when the latest amendment went in effect on 28/11/2003. Considering the fact that this topic is rarely addressed among Taiwan academics or practitioners, this article examines the American legal system and courts practices and attempts to interpret the current Taiwan Trademark Law in order to find the meaning

DuraChem trademark - challenges and solutions

International Nuclear Information System (INIS)

Howard, I.S.; Bowan, B.W.; Kirshe, M.H.

1996-01-01

Vitrification of low-level ion exchange resins represents numerous challenges never before successfully accomplished. These challenges include (1) Feed material preparation and transfer, (2) Melter temperature and volume control, (3) Glass composition, stabilization, and control, and (4) Off-gas treatment and particulate capture. The DuraChem trademark team of Chem-Nuclear Systems, Inc. and GTS Duratek, Inc. began its journey in 1994 and is in the process of starting-up the first centralized vitrification facility for commercial ion-exchange and filtration media. This paper addresses each of the challenges and provides an update of this unique volume-reduction and stabilization technology

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

2010-11-16

... applications. The seventh edition incorporates USPTO trademark practice and relevant case law reported prior to September 1, 2010. The policies stated in this revision supersede any previous policies stated in prior editions, examination guides, or any other statement of USPTO policy, to the extent that there is any...

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

Science.gov (United States)

2013-10-03

..., Analysis and Liaison Division, United States Patent and Trademark Office, Madison East Building, Room MDE... Federal eRulemaking Portal Web site will be made available for public inspection. Therefore, any... all comments received. To view the PTAG, please visit the USPTO's Web site at http://www.uspto.gov and...

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....

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.)

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.

7 CFR 1206.52 - Patents, copyrights, trademarks, information, publications, and product formulations.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, trademarks, information... Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research...

Strip-coat decontamination of ducting interiors with SEAMIST trademark -safe and fast

International Nuclear Information System (INIS)

Keller, C.

1994-01-01

The SEAMIST trademark system was invented for sampling and instrumentation of boreholes. However, the SEAMIST trademark pneumatically driven everting membrane has the ability to install absorbent liner materials for wicking and recovery of hazardous fluids (e.g., PCB'S) from ducting. The most useful vent cleaning technique is the installation of a stripcoat saturated duct liner which is then peeled from the liner retrieving contaminated particles (e. g., uranium, plutonium,...), much like the stripcoat which is used to clean glove boxes. Because of the everting SEAMIST trademark hole liner's ability to traverse ducting of many combinations of diameters, slope, turns, and obstructions, the stripcoat application method is exceptionally fast, (>10 ft/min.). This paper describes the method of installation, the prototype tests, the science, and the first results of a full scale test. This unusual method of cleaning ducting results in major advantages in safety, cost, and speed of the cleaning process. Comparisons are made with the traditional methods of sand blasting and washing. Additional benefits of the method are the ability to assess the distribution of the contamination of the ducting and to also use the everting membrane for a video camera examination of the cleaned duct coupled with contamination sensors, such as radiation logging tools. The technique can be extended to clean all manner of contamination in ducting such as microbial residues in hospitals. Very large ducts (12--120 inch dia.), are especially easily cleaned while still in place in the building

SEAMIST trademark in-situ instrumentation and vapor sampling system applications in the Sandia Mixed Waste Landfill Integrated Demonstration Program

International Nuclear Information System (INIS)

Lowry, W.E.; Dunn, S.D.; Cremer, S.C.; Williams, C.

1994-01-01

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. The current activities have 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 which allows easy emplacement and removal. Standard SEAMIST trademark vapor sampling systems were also integrated with state-of-the-art VOC analysis technologies (automated GC, UV laser fluorometer). The results and status of these demonstration tests are presented

Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer

Directory of Open Access Journals (Sweden)

Alhasan Elghouche

2016-01-01

Full Text Available We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity.

26 CFR 1.177-1 - Election to amortize trademark and trade name expenditures.

Science.gov (United States)

2010-04-01

... franchises or rights to the use of a trademark or trade name. Generally, section 177 will apply to... beginning after December 31, 1955, shall, within the time prescribed by law (including extensions thereof...

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.

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

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.

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

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.

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

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

. 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...

Trademarks, consumer protection and domain names on the Internet

Directory of Open Access Journals (Sweden)

Hana Kelblová

2007-01-01

Full Text Available The article deals with current problems of the conflict of domain names on the Internet with trade marks in relation to the consumer protection. The aim of the article is to refer to ways and means of protection against of the speculative registration of a domain name. In the Czech legal order these means represent legal regulation of the unfair competition in Commercial Code, regulation of liability for damage together with the Trademarks Act.

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.

APPLICATION OF THE LASAGNA(trademark) SOIL REMEDIATION TECHNOLOGY AT THE DOE PADUCAH GASEOUS DIFFUSION PLANT

International Nuclear Information System (INIS)

Swift, Barry D.; Tarantino, Joseph J. P. E.

2003-01-01

The Paducah Gaseous Diffusion Plant (PGDP), owned by the Department of Energy (DOE), has been enriching uranium since the early 1950s. The enrichment process involves electrical and mechanical components that require periodic cleaning. The primary cleaning agent was trichloroethene (TCE) until the late 1980s. Historical documentation indicates that a mixture of TCE and dry ice were used at PGDP for testing the integrity of steel cylinders, which stored depleted uranium. TCE and dry ice were contained in a below-ground pit and used during the integrity testing. TCE seeped from the pit and contaminated the surrounding soil. The Lasagna(trademark) technology was identified in the Record of Decision (ROD) as the selected alternative for remediation of the cylinder testing site. A public-private consortium formed in 1992 (including DOE, the U.S. Environmental Protection Agency, and the Kentucky Department for Environmental Protection, Monsanto, DuPont, and General Electric) developed the Lasagna(trademark) technology. This innovative technology employs electrokinetics to remediate soil contaminated with organics and is especially suited to sites with low permeability soils. This technology uses direct current to move water through the soil faster and more uniformly than hydraulic methods. Electrokinetics moves contaminants in soil pore water through treatment zones comprised of iron filings, where the contaminants are decomposed to basic chemical compounds such as ethane. After three years of development in the laboratory, the consortium field tested the Lasagna(trademark) process in several phases. CDM installed and operated Phase I, the trial installation and field test of a 150-square-foot area selected for a 120-day run in 1995. Approximately 98 percent of the TCE was removed. CDM then installed and operated the next phase (IIa), a year-long test on a 600-square-foot site. Completed in July 1997, this test removed 75 percent of the total volume of TCE down to a

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

Updated fracture incidence rates for the US version of FRAX (registered trademark)

Science.gov (United States)

Evaluation of results produced by the US version of FRAX (trademarked) indicates that this tool overestimates the likelihood of major osteoporotic fracture. In an attempt to correct this, we updated underlying baseline fracture rates for the model. We used US hospital discharge data from 2006 to ca...

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

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)

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.

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.

“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

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

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

Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could...... 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 c...

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

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.

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

Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

Science.gov (United States)

Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

2012-08-23

The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

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

MarCell trademark software for modeling bone marrow radiation cell kinetics

International Nuclear Information System (INIS)

Hasan, J.S.; Jones, T.D.; Morris, M.D.

1997-01-01

Differential equations were used to model cellular injury, repair, and compensatory proliferation in the irradiated bone marrow. Recently, that model was implemented as MarCell trademark, a user-friendly MS-DOS computer program that allows users from a variety of technical disciplines to evaluate complex radiation exposure. The software allows menu selections for different sources of ionizing radiation. Choices for cell lineages include progenitor, stroma, and malignant, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive feature is that any protracted irradiation can be compared with an equivalent prompt dose (EPD) in terms of cell kinetics for either the source used or for a reference such as 250 kVp x rays or 60 Co. EPD is used to mean a dose rate for which no meaningful biological recovery occurs during the period of irradiation. For human as species, output from MarCell trademark includes: risk of 30-day mortality; risk of whole-body cancer and leukemia based either on radiation-induced cytopenia or compensatory cell proliferation; cell survival and repopulation plots as functions of time or dose; and 4-week recovery following treatment. copyright 1997 American Association of Physicists in Medicine

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.

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.

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.

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

Science.gov (United States)

Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

2017-12-01

We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

Coil embolization of anterior circulation aneurysms supported by the solitaire trademark AB neurovascular remodeling device

International Nuclear Information System (INIS)

Klisch, Joachim; Clajus, Christin; Sychra, Vojtech; Eger, Cornelia; Strasilla, Christoph; Rosahl, Steffen; Gerlach, Ruediger; Baer, Ingrid; Hoch, Heinrich; Herbon, Uta; Borota, Ljubisa; Jonasson, Per; Liebig, Thomas

2010-01-01

The purpose of the study is to evaluate patients with wide-necked or complex aneurysms of the anterior circulation who underwent Solitaire trademark AB Neurovascular Remodeling Device-assisted coil embolization. From February 2008 to March 2009, consecutive data were collected from 45 patients with anterior circulation aneurysms. Eighteen of the patients presented with acute subarachnoid hemorrhage. Forty-six aneurysms were treated with the aid of different applications (n=49) of the Solitaire trademark AB Remodeling Device followed by standard coiling procedure (n = 43) using bioactive coils or/and bare coils. Successful positioning of the remodeling device was obtained in 95.9% of the cases. There were two thromboembolic complications (4.1%) and one severe vasospasm requiring retrieval of the device. Permanent procedural morbidity was observed in one patient (2%). The proportion of patients in whom Raymond class 1 occlusion was obtained was 53.5% (n=23). Raymond class 2 occlusion was achieved in 42% (n=18) and Raymond class 3 occlusion in 4.7% (n=2). Thirty-nine patients left the hospital with a good clinical status. The initial technical and clinical results of Solitaire trademark AB device-assisted coiling of aneurysms in the anterior circulation are highly encouraging. This technique may enhance the possibilities of the endovascular treatment of these aneurysms in clinical routine. (orig.)

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

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

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.

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

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 contain Chapter 18 -- Human Factors Engineering. Topics covered include: design team organization and responsibilities; design goals and design bases; design process and application to human factors engineering; functional task analysis; control room configuration; information presentation and panel layout evaluation; control and monitoring outside the main control room; and verification and validation

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

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.

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

Identification of markers that functionally define a quiescent multiple myeloma cell sub-population surviving bortezomib treatment

International Nuclear Information System (INIS)

Adomako, Alfred; Calvo, Veronica; Biran, Noa; Osman, Keren; Chari, Ajai; Paton, James C; Paton, Adrienne W; Moore, Kateri; Schewe, Denis M; Aguirre-Ghiso, Julio A

2015-01-01

The mechanisms allowing residual multiple myeloma (MM) cells to persist after bortezomib (Bz) treatment remain unclear. We hypothesized that studying the biology of bortezomib-surviving cells may reveal markers to identify these cells and survival signals to target and kill residual MM cells. We used H2B-GFP label retention, biochemical tools and in vitro and in vivo experiments to characterize growth arrest and the unfolded protein responses in quiescent Bz-surviving cells. We also tested the effect of a demethylating agent, 5-Azacytidine, on Bz-induced quiescence and whether inhibiting the chaperone GRP78/BiP (henceforth GRP78) with a specific toxin induced apoptosis in Bz-surviving cells. Finally, we used MM patient samples to test whether GRP78 levels might associate with disease progression. Statistical analysis employed t-test and Mann-Whitney tests at a 95% confidence. We report that Bz-surviving MM cells in vitro and in vivo enter quiescence characterized by p21 CIP1 upregulation. Bz-surviving MM cells also downregulated CDK6, Ki67 and P-Rb. H2B-GFP label retention showed that Bz-surviving MM cells are either slow-cycling or deeply quiescent. The Bz-induced quiescence was stabilized by low dose (500nM) of 5-azacytidine (Aza) pre-treatment, which also potentiated the initial Bz-induced apoptosis. We also found that expression of GRP78, an unfolded protein response (UPR) survival factor, persisted in MM quiescent cells. Importantly, GRP78 downregulation using a specific SubAB bacterial toxin killed Bz-surviving MM cells. Finally, quantification of Grp78 high /CD138+ MM cells from patients suggested that high levels correlated with progressive disease. We conclude that Bz-surviving MM cells display a GRP78 HIGH /p21 HIGH /CDK6 LOW /P-Rb LOW profile, and these markers may identify quiescent MM cells capable of fueling recurrences. We further conclude that Aza + Bz treatment of MM may represent a novel strategy to delay recurrences by enhancing Bz

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

Applying Strategic Visualization(Registered Trademark) to Lunar and Planetary Mission Design

Science.gov (United States)

Frassanito, John R.; Cooke, D. R.

2002-01-01

NASA teams, such as the NASA Exploration Team (NEXT), utilize advanced computational visualization processes to develop mission designs and architectures for lunar and planetary missions. One such process, Strategic Visualization (trademark), is a tool used extensively to help mission designers visualize various design alternatives and present them to other participants of their team. The participants, which may include NASA, industry, and the academic community, are distributed within a virtual network. Consequently, computer animation and other digital techniques provide an efficient means to communicate top-level technical information among team members. Today,Strategic Visualization(trademark) is used extensively both in the mission design process within the technical community, and to communicate the value of space exploration to the general public. Movies and digital images have been generated and shown on nationally broadcast television and the Internet, as well as in magazines and digital media. In our presentation will show excerpts of a computer-generated animation depicting the reference Earth/Moon L1 Libration Point Gateway architecture. The Gateway serves as a staging corridor for human expeditions to the lunar poles and other surface locations. Also shown are crew transfer systems and current reference lunar excursion vehicles as well as the Human and robotic construction of an inflatable telescope array for deployment to the Sun/Earth Libration Point.

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

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...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... 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...

Syringolin A selectively labels the 20 S proteasome in murine EL4 and wild-type and bortezomib-adapted leukaemic cell lines.

Science.gov (United States)

Clerc, Jérôme; Florea, Bogdan I; Kraus, Marianne; Groll, Michael; Huber, Robert; Bachmann, André S; Dudler, Robert; Driessen, Christoph; Overkleeft, Herman S; Kaiser, Markus

2009-11-02

The natural product syringolin A (SylA) is a potent proteasome inhibitor with promising anticancer activities. To further investigate its potential as a lead structure, selectivity profiling with cell lysates was performed. At therapeutic concentrations, a rhodamine-tagged SylA derivative selectively bound to the 20 S proteasome active sites without detectable off-target labelling. Additional profiling with lysates of wild-type and bortezomib-adapted leukaemic cell lines demonstrated the retention of this proteasome target and subsite selectivity as well as potency even in clinically relevant cell lines. Our studies, therefore, propose that further development of SylA might indeed result in an improved small molecule for the treatment of leukaemia.

关键词推广使用他人商标的反不正当竞争法规制%The Regulation on Anti-unfair Competition of Using Others’ Trademarks as Keyword Promotion

Institute of Scientific and Technical Information of China (English)

刘润涛

2016-01-01

There is an ongoing debate on the attributes of trademarks that only be used as keywords of search engine promotion, namely trademark infringement, unfair competition or legitimate use. There are many different judgments in judicial practice. This paper begins from the theory and practice of trademark use in keyword promotion, and argues that the behavior that trademarks are used only as keywords does not belong to trademark use in trademark law, and it is not easy to confuse the public. Although trademark use as keyword promotion does not constitute trademark infringement in trademark law, it may be adjusted by anti-unfair competition law if it is achieved by unfair means and clearly violates the principle of honesty and credit and the generally recognized business ethics. Otherwise, the law should not intervene and leave the market to choose. We should prevent improperly expanding the application of anti-unfair competition to hinder the free competition, and carry out the legal policy of promoting innovation and encouraging free competition.%仅将他人商标用作关键词进行搜索引擎推广，是商标侵权行为、不正当竞争行为抑或不侵权，争议较大，司法实践很多判决出现截然不同的结果。文章从关键词推广是否构成商标使用的理论与实践梳理入手，分析仅将他人的商标用作搜索关键词不属于商标使用，不会导致相关公众混淆。

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

Science.gov (United States)

Fenske, Timothy S; Shah, Namrata M; Kim, Kyung Mann; Saha, Sandeep; Zhang, Chong; Baim, Arielle E; Farnen, John P; Onitilo, Adedayo A; Blank, Jules H; Ahuja, Harish; Wassenaar, Tim; Qamar, Rubina; Mansky, Patrick; Traynor, Anne M; Mattison, Ryan J; Kahl, Brad S

2015-10-01

Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL. © 2015 American Cancer Society.

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

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.

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.

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

Science.gov (United States)

2010-07-09

... plan includes the USPTO's mission statement, vision statement and a description of the strategic goals... achieve its vision. Full details on how the USPTO plans to implement the strategic plan, including funding...] United States Patent and Trademark Office Draft Strategic Plan for FY 2010-2015 AGENCY: United States...

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.

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…

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.

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

The Protection of Sports Trademarks in the Recent Case Law of the Court of Justice of the European Union = Ochrona sportowych znaków towarów w świetle najnowszego orzecznictwa TSUE

Directory of Open Access Journals (Sweden)

Paweł Szwajdler

2016-03-01

Nicolaus Copernicus University in Torun, Poland       Abstract               The main aim of this work is to give an answer to the question: are sports trademarks treated in EU in different way than other trademarks?  The author of this article was inspired by two recent judgements of EU Court of Justice. First of them is related to sports shoes and second one to football club crest. Above- mentioned judgement are interesting, because both of them concern marks, which are similar to registered trademarks. Therefore, it is able to show boundaries of the protection of sports trademarks.  This paper contains also overall considerations about trademarks, sports trademarks and their protection.   Abstrakt               Głównym celem niniejszego artykułu jest udzielenie odpowiedzi na pytanie, czy sportowe znaki towarowe podlegają w Unii Europejskiej szczególnej ochronie prawnej. Inspirację dla zarysowanych w zdaniu poprzednim rozważań stanowią dwa wyroki Trybunału Sprawiedliwości Unii Europejskiej. Pierwszy spośród nich dotyczy ochrony konturów herbu klubu piłkarskiego, natomiast drugi dotyka problemów związanych z charakterystycznym znakiem umieszczanym na produktach znanej marki butów sportowych. Omawiane w niniejszej pracy wyroki są wyjątkowo interesujące, ponieważ wiążą się z ochroną znaków li tylko przypominających zarejestrowane ZTUE. Artykuł zawiera również ogólne refleksje na temat znaków towarowych, sportowych znaków towarowych oraz przeciwdziałania ich naruszeniom.   Słowa kluczowe: sport, znak towarowy, TSUE, prawo własności intelektualnej, sportowy znak towarowy Key word: sport, trademark, sports trademark, EU Court of Justice, intellectual property rights

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

Thermoluminescent signal fading of encapsulated lif: Mg,Ti detectors in PTFE-Teflon registered trademark

International Nuclear Information System (INIS)

Sasho Nikolovski, Sasho; Nikolovska, Lidija; Velevska, Marija; Velev, Velko

2010-01-01

Fading is a process when the latent information of a detector is unintentionally lost mainly due to the thermal influence. Thermoluminescent (TL) detectors have different sensitivities as far as the fading effect. Encapsulated TL detectors mounted within shielded filter holders are used during the personal monitoring of occupationally exposed persons in R. Macedonia. PTFE-Teflon registered trademark polymer is an example of encapsulation material that has a temperature resistance and it allows the luminescence signal to pass through. Since the encapsulated TL detectors cannot be submitted to annealing treatment in an oven, another fading reduction method is needed. The TL evaluation method suggested in this work is based on a specific glow-curve region. Irradiations were conducted using 90Sr/90Y source. Post-irradiation fade investigations were conducted for evaluation periods that varied up to 4 months. Two areas of the TL glow-curve were selected with the WimRems software. They correspond to the high and the low fading emission peaks (the lower temperature peaks display a greater degree of thermal fading than the higher temperature peaks). Post-irradiation fade is a contributing factor that affects the response of a thermoluminescent (TL) phosphor as a function of time. PTFE - Polytetrafluoroethylene most well known by the DuPont brand name Teflon registered trademark. (Author)

Absorption of uv-radiation by Chibro trademark -Uvelin eye drops

International Nuclear Information System (INIS)

Schreder, J.G.; Blumthaler, M.; Daxer, A.; Ettl, A.

1998-01-01

The preparation Chibro trademark -Uvelin is recommended against both solar and artificial uv-radiation. At wavelengths greater than 290 nm and at an effective layer thickness of 10 μm measurements with a high resolution doublemonochromator showed a transmission larger than 90%. The solar spectrum is characterised by almost no irradiance on the earth's surface for wavelengths smaller than 290 nm due to absorption in the atmospheric ozon layer. Therefore, no significant protective effect of the eye-drops against keratitis and cataract under solar exposure can be expected. A significantly better sagging of the radiation of artificial UV-sources with a high amount of UV-C is reached. The recommended application as chemical protective goggles in this spectral range is not permissible. (orig.) [de

Results of immunoscintigraphy of osteomyelitis (LeukoScan) {sup trademark}; Ergebnisse zur Immunszintigraphie der Osteomyelitis (LeukoScan) {sup trademark}

Energy Technology Data Exchange (ETDEWEB)

Gratz, S.; Becker, W. [Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin

2000-05-01

99mTc-labeled antigranulocyte monoclonal antibody Fab' fragments have shown a high sensitivity and specificity for detecting osteomyelitis in prospective studies. We retrospectively evaluated the use of LeukoScan {sup trademark} (Immunomedics, Morris Plains, N.J.) in clinical routine for the detection of bone and soft tissue infections and we want to present the results of our findings as well as some of the more interesting cases in this occasion. Imaging infection can be performed fast and easy with {sup 99m}Tc-Fab' fragments due to a fast targeting of infection and good background clearance, which increases in imaging quality. The application of {sup 99m}Tc-Fab' fragments gives good results in patients with bone and soft tissue infections of peripheral bones, as well as in patients with infected prostheses and infected arthritis. The use of {sup 99m}Tc-Fab' fragments should not be limited to these patients only, since good results can also be achieved in patients with infections of vascular grafts, of appendicitis and of endocarditis as well. A higher number of false-negative results has to be expected in case of subacute/chronic infections instead. Independent of the grade of infection acute/subacute infections of the spine always show 'cold lesions'. If cold lesions are used as guide for diagnosing a pathologic finding, an increase in sensitivity together with a decrease in specificity can be achieved. (orig.) [German] {sup 99m}Tc-markierte Antigranulozytenantikoerper-Fab'-Fragmente konnten in prospektiven Studien eine hohe Sensitivitaet und Spezifitaet bei der Detektion von Osteomyelitiden unter Beweis stellen. Retrospektiv haben wir die Anwendung von {sup 99m}Tc-markierten Fab'-Fragmenten ({sup 99m}Tc-Fab') (LeukoScan {sup trademark}, Immunomedics, Morris Plains, N.J.) in der klinischen Routine zum Nachweis von Knochen- und Weichteilentzuendungen ausgewertet und moechten einen Teil unserer Ergebnisse sowie einige

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

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.

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.

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…

GenMol trademark supramolecular descriptors predicting reliable sensitivity of energetic compounds

Energy Technology Data Exchange (ETDEWEB)

Benazet, Stephane; Jacob, Guy [SNPE Materiaux Energetiques, Vert Le Petit (France); Pepe, Gerard [CINaM UPR-CNRS 3118, Campus de Luminy Case, Marseille (France)

2009-04-15

Structure/activity relationship methodology has been applied to the problem of the prediction of the energetic molecule's sensitivity. This parameter knowledge is of great importance to increase the safety of operations in the field of synthesis and manipulation of such compounds. It has been shown that descriptors of the solid state interactions and surface topology issued from GenMol {sup trademark} software calculations greatly enhanced the correlation between measured and predicted sensitivity. As the structural parameters used to establish the descriptors are experimental ones, their physical significance is particularly preserved which allows to give a good prediction for impact or friction sensitivity by the so defined descriptors. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

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…

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

Directory of Open Access Journals (Sweden)

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.

小微企业实施商标战略的困境与对策%PREDICAMENT AND COUNTERMEASURES OF SMALL & MICRO-BUSINESSES IN IMPLEMENTING TRADEMARK STRATEGY

Institute of Scientific and Technical Information of China (English)

李文江; 郭雨洁

2015-01-01

The existence and development of small and micro enterprises give not only strong support to the de-velopment of the national economy,but also provide vast space for national employment. Therefore governments at all levels have gradually introduced a number of supportive policies. Following the successive promulgation of the strategy of developing the country through science and technology and the strategy of intellectual proper-ty,technology-based small and micro-businesses attach greater importance to the role of intellectual property in the development of enterprises,such as brand development,patented technology and so on. However,in prac-tice,small and micro-businesses are faced with not only some misunderstanding as to how to cultivate and es-tablish their own brands through trademark registration,such as passing off a famous brand,paying no attention to registered trademark,ignoring the use of registered trademarks and so on,they are also plagued by the exist-ing system including restricted personal trademark applications,inconvenient electronic filing,rejecting and re-viewing application at higher costs. Small and micro enterprises should choose proper trademark strategy ac-cording to their own characteristics,such as small scale,weak in strength and low productivity. The State Trademark Bureau should effectively support the development of small and micro-businesses through the revi-sion of trademark law which will optimize and refine trademark registration rules.%小微企业的存在与发展不仅有力支撑了国民经济的发展，而且成为国民就业的广阔空间，为此，我国各级政府都陆续出台了许多扶持政策。在科技兴国战略和知识产权战略相继颁布后，科技�

Precombustion desulfurization using Microcel{trademark} and multi-gravity separator

Energy Technology Data Exchange (ETDEWEB)

Yoon, R.H.; Luttrell, G.H.; Venkatraman, P. [Virginia Polytechnic Institute and State Univ., Blacksburg, VA (United States)

1994-12-31

Studies conducted at the Center for Coal and Minerals Processing (CCMP) indicate that surface-based processes such as froth flotation are inefficient in removing pyrite from fine coal. This shortcoming has been attributed to the fact that pyrite can become hydrophobic under certain conditions and to the inability of flotation to reject middling particles. To overcome these deficiencies, a new processing scheme has been developed at CCMP which involved the use of the Microcel{trademark} flotation column in combination with a centrifugal flowing-film separator, called a Multi-Gravity Separator (MGS). The flotation column removes ash-forming minerals such as clay, while the MGS is effective in removing pyrite. Preliminary test data obtained with high-sulfur coals shows that this processing scheme can nearly double the pyritic sulfur rejection with little loss in clean coal yield. This article discusses the underlying principles of the new circuit and provides test results obtained using eastern U.S. coals.

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.

Full scaled tests of the KERENA trademark containment cooling condenser at the INKA test facility

International Nuclear Information System (INIS)

Leyer, Stephan; Maisberger, Fabian; Lineva, Natalia; Wagner, Thomas; Doll, Mathias; Herbst, Vasilli; Wich, Michael

2010-01-01

KERENA trademark is a medium-capacity boiling water reactor. It combines passive safety systems with active safety equipment of service-proven design. The passive systems utilize basic laws of physics, such as gravity and natural convection, enabling them to function without any power supply or actuation by instrumentation and control (I and C) equipment. They are designed to bring the plant to a safe and stable condition without the aid of active systems. Furthermore, the passive safety features partially replace the active systems, which reduces costs significantly and provides a safe, reliable and economically competitive plant design. At the new test facility at Karlstein called INKA (Integral Test Stand Karlstein), the key components of the KERENA trademark passive safety concept - the Emergency Condenser (EC), the Containment Cooling Condenser (CCC) and the passive core flooding system (PCFS) - are presently under full-scale testing,. Integral system tests will also be performed to show how the passive safety systems interact under various anticipated accident conditions and to demonstrate the ability of the passive systems to bring the plant to a safe and stable condition without the aid of active systems or actuation by I and C signals. The passive pressure pulse transmitter (PPPT) will be included in these integral tests. In this report the experimental setup and the first test results with the full scaled Containment Cooling Condenser will be described. (orig.)

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.

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

International Nuclear Information System (INIS)

Dunn, S.D.; Lowry, W.; Walsh, R.; Rao, D.V.; Williams, C.

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

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.

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

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...

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.

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…

Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells.

Science.gov (United States)

Rossi, Ursula A; Finocchiaro, Liliana M E; Glikin, Gerardo C

2017-01-01

Malignant melanoma is a fast growing form of skin cancer with increasing global incidence. Clinically, canine malignant melanoma and human melanoma share comparable treatment-resistances, metastatic phenotypes and site selectivity. Both interferon-β (IFNβ) and bortezomib (BTZ) display inhibitory activities on melanoma cells. Here, we evaluated the cytotoxic effects of the combination of BTZ and IFNβ gene lipofection on cultured melanoma cell lines. Cell viability determined by the acid phosphatase method, cell migration mesasured by the wound healing assay, DNA fragmentation and cell cycle by flow cytometry after propidium iodide staining and reactive oxygen species (ROS) production by H2DCF-DA fluorescence. Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNβ transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration. The combined treatment produced a significant raise of apoptosis evidenced by DNA fragmentation as compared to either BTZ or IFNβ gene lipofection single treatments. Furthermore, BTZ significantly increased the intracellular ROS generation induced by IFNβ gene transfer in melanoma cells, an effect that was reversed by the addition of the ROS inhibitor N-acetyl-L-cystein. The present work encourages further studies about the potential of the combination of interferon gene transfer with proteasome inhibitors as a new combined therapy for malignant melanoma, both in veterinary and/or human clinical settings. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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

Pipe explorer trademark: Overview, applications, and recent developments

International Nuclear Information System (INIS)

Kendrick, D.T.; Cremer, C.D.

1996-01-01

As the Department of Energy (DOE) continues to dismantle its nuclear process facilities, site managers throughout the complex must employ the safest and most cost effective means of disposing or remediating hundreds of miles of potentially contaminated piping and duct work. Much of this is buried or encased, making quantification of contamination levels inside the pipes extremely difficult. Without adequate characterization, it is usually necessary to assume the piping is contaminated and to extract and dispose of it accordingly. For buried drain lines this approach can cost on the order of $1,200/ft and is often unnecessary as residual contamination levels are below free release criteria. The Science ampersand Engineering Associates, Inc. (SEA) Pipe Explorer trademark technology offers a simple and effective approach of transporting characterization tools into pipes and ducts so that these costs can be avoided. The system uses a pneumatically operated tubular membrane to tow radiation detectors and video cameras into pipes while simultaneously providing a clean conduit for the sensors to travel through. This paper describes the operation of the system, the DOE sites where it has been used, and the cost savings that have resulted from its use. In addition, recently added features to the technology, such as the ability to perform alpha and video surveys, are discussed

Regulatory issues resolved through design certification on the System 80+trademark standard plant design

International Nuclear Information System (INIS)

Ritterbusch, S.E.; Brinkman, C.B.

1996-01-01

The US Nuclear Regulatory Commission (NRC) has completed its review of the System 80+trademark Standard Plant Design, approving advanced design features and closing severe accident licensing issues. Final Design Approval was granted in July 1994. The NRC review was extensive, requiring written responses to over 4,950 questions and formal printing of over 50,000 Safety Analysis Report pages. New safety issues never before addressed in a regulatory atmosphere had to be resolved with detailed analysis and evaluation of design features. the System 80+ review demonstrated that regulatory issues can be firmly resolved only through presentation of a detailed design and completion of a comprehensive regulatory review

Accelerated hydrocarbon removal with the NoVOCs trademark process

International Nuclear Information System (INIS)

Dawson, G.W.; McKeon, T.J.

1996-01-01

It has been estimated that by 1990, there were over 240,000 leaking underground storage tanks in the US and that the majority of those tanks had contained some type of petroleum fuel. The resulting hydrocarbon contamination from those leaking tanks became the focus of a significant amount of environmental restoration effort. Free product was collected and removed from the water table. Contaminated soils were excavated for thermal desorption or land farming, or aerated in place to promote bioremediation. Affected ground water was withdrawn by means of extraction wells and routed to air stripping towers or, more recently, stripped in place with in situ air sparging. NoVOCs trademark is a patented design for the application of in-well stripping as an alternative to pump and treat systems over which it offers two unique advantages: (1) Development of a circulation pattern within the saturated zone that optimizes dissolution and transport of contaminants to the well; and (2) Separation of the volatile contaminants for the ground water in the well so that only vapor is transported above ground and there are no water discharges to be managed

CPICOR{trademark}: Clean power from integrated coal-ore reduction

Energy Technology Data Exchange (ETDEWEB)

Wintrell, R.; Miller, R.N.; Harbison, E.J.; LeFevre, M.O.; England, K.S.

1997-12-31

The US steel industry, in order to maintain its basic iron production, is thus moving to lower coke requirements and to the cokeless or direct production of iron. The US Department of Energy (DOE), in its Clean Coal Technology programs, has encouraged the move to new coal-based technology. The steel industry, in its search for alternative direct iron processes, has been limited to a single process, COREX{reg_sign}. The COREX{reg_sign} process, though offering commercial and environmental acceptance, produces a copious volume of offgas which must be effectively utilized to ensure an economical process. This volume, which normally exceeds the internal needs of a single steel company, offers a highly acceptable fuel for power generation. The utility companies seeking to offset future natural gas cost increases are interested in this clean fuel. The COREX{reg_sign} smelting process, when integrated with a combined cycle power generation facility (CCPG) and a cryogenic air separation unit (ASU), is an outstanding example of a new generation of environmentally compatible and highly energy efficient Clean Coal Technologies. This combination of highly integrated electric power and hot metal coproduction, has been designated CPICOR{trademark}, Clean Power from Integrated Coal/Ore Reduction.

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

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).

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

Results of immunoscintigraphy of osteomyelitis (LeukoScan) trademark

International Nuclear Information System (INIS)

Gratz, S.; Becker, W.

2000-01-01

99mTc-labeled antigranulocyte monoclonal antibody Fab' fragments have shown a high sensitivity and specificity for detecting osteomyelitis in prospective studies. We retrospectively evaluated the use of LeukoScan trademark (Immunomedics, Morris Plains, N.J.) in clinical routine for the detection of bone and soft tissue infections and we want to present the results of our findings as well as some of the more interesting cases in this occasion. Imaging infection can be performed fast and easy with 99m Tc-Fab' fragments due to a fast targeting of infection and good background clearance, which increases in imaging quality. The application of 99m Tc-Fab' fragments gives good results in patients with bone and soft tissue infections of peripheral bones, as well as in patients with infected prostheses and infected arthritis. The use of 99m Tc-Fab' fragments should not be limited to these patients only, since good results can also be achieved in patients with infections of vascular grafts, of appendicitis and of endocarditis as well. A higher number of false-negative results has to be expected in case of subacute/chronic infections instead. Independent of the grade of infection acute/subacute infections of the spine always show 'cold lesions'. If cold lesions are used as guide for diagnosing a pathologic finding, an increase in sensitivity together with a decrease in specificity can be achieved. (orig.) [de

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.

Characterization of radioactive contamination inside pipes with the Pipe Explorer{sup trademark} system

Energy Technology Data Exchange (ETDEWEB)

Cremer, C.D.; Lowry, W.; Cramer, E. [Science and Engineering Associates, Inc., Albuquerque, NM (United States)] [and others

1995-10-01

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. Historically, this has been attempted using hand held survey instrumentation, surveying only the accessible exterior portions of pipe systems. Difficulty, or inability of measuring threshold surface contamination values, worker exposure, and physical access constraints have limited the effectiveness of this approach. 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.

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

Report on the performance and operating characteristics of the Burle C83061E QUANTACON trademark photomultiplier tube

International Nuclear Information System (INIS)

Sandberg, V.D.; Thompson, T.N.; Helvy, F.A.

1989-01-01

The Burle C83061E QUANTACON trademark is a 10.4 inch diameter photomultiplier tube with improved photoelectron collection optics. We report here on the first tests of this newly developed tube. We find the single photoelectron charge resolution to be excellent, with a peak to (noise) valley ratio exceeding 3 and with a transit time spread of less than 2.3 ns (FWHM) for full photocathode illumination at the single photoelectron level. A design for a fast anode pulse base is also presented. 11 refs., 8 figs

SENTINEL trademark technical basis report for Peach Bottom. Final report

International Nuclear Information System (INIS)

1998-04-01

PECO Energy in cooperation with the Electric Power Research Institute (EPRI) installed the SENTINEL trademark software at its Peach Bottom Atomic Power Station (PBAPS). 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 nine months, 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 PBAPS 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

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.

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.

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

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.

Mechanical properties of Nextel trademark 312 fiber-reinforced SiC matrix composites

International Nuclear Information System (INIS)

Vaidyanathan, K.R.; Sankar, J.; Kelkar, A.D.; Weaver, B.

1995-01-01

Vapor phase synthesis is emerging as a method for the preparation of near final-shape, ceramic matrix composites for advanced structural applications. Oxide fiber-reinforced silicon carbide matrix composites are currently being developed for these applications. The mechanical properties of Nextel trademark 312 fiber reinforced SiC matrix composites fabricated employing the forced-flow, thermal gradient chemical vapor infiltration process (FCVI) were evaluated at room temperature in pure tension. The composites were fabricated with a 0.15 μm pyrolytic carbon interface layer for improving the toughness of the composite system. Because of the available FCVI apparatus, only short length specimens (7--8 cm) could be fabricated. Room temperature tensile strengths were measured and compared to room temperature flexure strength results for the composite. Excellent toughness and composite behavior was obtained for the composite system. Fractography as well as possible factors responsible for the differences in tensile and flexural strengths for the composite system is presented in this paper

Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation

Directory of Open Access Journals (Sweden)

Tomás J. González-López

2011-11-01

Full Text Available A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin k light chain. The presence of a small population of monoclonal plasmacytes producing an only light k monoclonal component was demonstrated and Bortezomib and Dexamethasone (BD was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR the patient underwent high dose of melphalan (HDM and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

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

DIWA trademark. AREVA's approach of intelligent computer-aided support of water chemistry monitoring in power plants

International Nuclear Information System (INIS)

Fandrich, Joerg

2011-01-01

The complexity of power plant operation makes stringent demands on the chemical quality of the coolant in process systems and loops. Optimal water chemistry ensures high corrosion resistance of these systems and is thus essential for safe and economic long term plant operation. The market offers a huge variety of commercial software packages for water chemistry control. Most of these computer programs have to be considered as data analysis or, respectively, data acquisition programs. Some of them require manual data input (Laboratory Information Management Systems), others are capable of performing a fully automated data acquisition. However, the plant operator typically is left alone with the actual interpretation of all collected and validated data, which would be the main characteristic feature of an analysis (or monitoring) system. The data validation is typical being performed by means of numerical methods in the broadest sense. This activity requires a long working experience and specific skills by the plant chemistry operator. True diagnostic systems need to be significantly more advanced. They contain the capability of data interpretation and derivation of specific diagnoses. This is combined with additional explanations on how the diagnoses were derived. Additionally, further recommendations are offered on how to proceed to reach the normal operational behavior as soon as possible. AREVA's DIWA trademark system features a fuzzy logic expert system that is based on expert knowledge. It is built on symptoms, which are combined in rules as part of the fuzzy tool set. These components can be edited without programming knowledge, which significantly reduces training efforts. It makes the system more robust, more compact and simpler compared to other so-called expert systems. DIWA trademark represents the knowledge in a natural way, in which other conventional expert system may have difficulties or need a larger set of rule algorithms. (orig.)

Effects of Heating on Teflon(Registered Trademark) FEP Thermal Control Material from the Hubble Space Telescope

Science.gov (United States)

deGroh, Kim; Gaier, James R.; Hall, Rachelle L.; Norris, Mary Jo; Espe, Matthew P.; Cato, Daveen R.

1999-01-01

Metallized Teflon(Registered Trademark) FEP (fluorinated ethylene propylene) thermal control material on the Hubble Space Telescope (HST) is degrading in the space environment. Teflon(Registered Trademark) FEP thermal control blankets (space-facing FEP) retrieved during the first servicing mission (SM1) were found to be embrittled on solar facing surfaces and contained microscopic cracks. During the second servicing mission (SM2) astronauts noticed that the FEP outer layer of the multi-layer insulation (MLI) covering the telescope was cracked in many locations around the telescope. Large cracks were observed on the light shield, forward shell and equipment bays. A tightly curled piece of cracked FEP from the light shield was retrieved during SM2 and was severely embrittled, as witnessed by ground testing. A Failure Review Board (FRB) was organized to determine the mechanism causing the MLI degradation. Density, x-ray crystallinity and solid state nuclear magnetic resonance (NMR) analyses of FEP retrieved during SM1 were inconsistent with results of FEP retrieved during SM2. Because the retrieved SM2 material curled while in space, it experienced a higher temperature extreme during thermal cycling, estimated at 200 C, than the SM1 material, estimated at 50 C. An investigation on the effects of heating pristine and FEP exposed on HST was therefore conducted. Samples of pristine. SM1, and SM2 FEP were heated to 200 C and evaluated for changes in density and morphology. Elevated temperature exposure was found to have a major impact on the density of the retrieved materials. Characterization of polymer morphology of as-received and heated FEP samples by NMR provided results that were consistent with the density results. These findings have provided insight to the damage mechanisms of FEP in the space environment.

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.)

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.

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

Directory of Open Access Journals (Sweden)

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

Waste Tank Vapor Project: Vapor characterization of Tank 241-C-103: Report for SUMMA trademark canister samples received 11/29/93 (sample jobs 4 and 5)

International Nuclear Information System (INIS)

Clauss, T.R.; Lucke, R.B.; McVeety, B.; Allwine, K.J.; Fruchter, J.S.

1994-09-01

The purpose of Sample Jobs 4 and 5 was to determine whether the organic nitrites observed on the outside of tank 241-C-103 originated in the tank or from degradation products of the high-efficiency particulate air (HEPA) filter. The plan was to take samples from either side of the HE-PA filter. The relative level of organic nitrites would help determine whether they were produced in the filter or the tank. Pacific Northwest Laboratory was responsible for analyzing the SUMMA trademark canisters collected in support of this study. The laboratory was to analyze the SUMMA trademark Canister samples according to letters of instruction and report all semivolatile and volatile organic constituents detected in the tank headspace. Pacific Northwest Laboratory was also to submit a letter report to the Program Manager of all qualitative and quantitative analytical data, and estimate concentrations of any aliphatic nitrites identified. This was one of the first sampling activities for this program, and a number of errors were made both in the field and in the laboratory. Because of these errors, the samples and results were of questionable value. Therefore, Westinghouse program management asked that the analysis of the samples for this report not be completed. This report describes the few results that were generated before we were asked to stop work on this activity. In addition to analyzing SUMMA trademark canisters, PNL operates a site portable weather station near tank 241-C-103. Pacific Northwest Laboratory was required to collect atmospheric data starting 11/15/93, but the weather station was already collecting data during the time of both these two sample jobs (11/12/93 and 11/16/93). Therefore, a summary of the atmospheric data is also presented in this report

NIK is required for NF-κB-mediated induction of BAG3 upon inhibition of constitutive protein degradation pathways.

Science.gov (United States)

Rapino, F; Abhari, B A; Jung, M; Fulda, S

2015-03-12

Recently, we reported that induction of the co-chaperone Bcl-2-associated athanogene 3 (BAG3) is critical for recovery of rhabdomyosarcoma (RMS) cells after proteotoxic stress upon inhibition of the two constitutive protein degradation pathways, that is, the ubiquitin-proteasome system by Bortezomib and the aggresome-autophagy system by histone deacetylase 6 (HDAC6) inhibitor ST80. In the present study, we investigated the molecular mechanisms mediating BAG3 induction under these conditions. Here, we identify nuclear factor-kappa B (NF-κB)-inducing kinase (NIK) as a key mediator of ST80/Bortezomib-stimulated NF-κB activation and transcriptional upregulation of BAG3. ST80/Bortezomib cotreatment upregulates mRNA and protein expression of NIK, which is accompanied by an initial increase in histone H3 acetylation. Importantly, NIK silencing by siRNA abolishes NF-κB activation and BAG3 induction by ST80/Bortezomib. Furthermore, ST80/Bortezomib cotreatment stimulates NF-κB transcriptional activity and upregulates NF-κB target genes. Genetic inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor (IκBα-SR) or by knockdown of p65 blocks the ST80/Bortezomib-stimulated upregulation of BAG3 mRNA and protein expression. Interestingly, inhibition of lysosomal activity by Bafilomycin A1 inhibits ST80/Bortezomib-stimulated IκBα degradation, NF-κB activation and BAG3 upregulation, indicating that IκBα is degraded via the lysosome in the presence of Bortezomib. Thus, by demonstrating a critical role of NIK in mediating NF-κB activation and BAG3 induction upon ST80/Bortezomib cotreatment, our study provides novel insights into mechanisms of resistance to proteotoxic stress in RMS.

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.

Synergistic suppression of the PI3K inhibitor CAL-101 with bortezomib on mantle cell lymphoma growth

International Nuclear Information System (INIS)

Qu, Fu-Lian; Xia, Bing; Li, Su-Xia; Tian, Chen; Yang, Hong-Liang; Li, Qian; Wang, Ya-Fei; Yu, Yong; Zhang, Yi-Zhuo

2015-01-01

To investigate the effects of CAL-101, particularly when combined with bortezomib (BTZ) on mantle cell lymphoma (MCL) cells, and to explore its relative mechanisms. MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups: control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B (NF-κB) of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ

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

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

Performance evaluation of the PITBULL trademark pump for the removal of hazardous waste

International Nuclear Information System (INIS)

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

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.)

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

The PERC trademark process: Existing and potential applications for induction coupled plasma technology in hazardous and radioactive waste treatment

International Nuclear Information System (INIS)

Blutke, A.S.; Vavruska, J.S.; Serino, J.F.

1996-01-01

Plasma Technology, Inc. (PTI), a Santa Fe, New Mexico corporation has developed the Plasma Energy Recycle and Conversion (PERC)trademark treatment process as a safe and environmentally clean alternative to conventional thermal destruction technologies. The PERC trademark treatment process uses as its heat source an advanced Induction Coupled Plasma (ICP) torch connected to a reaction chamber system with an additional emission control system. For example, organic-based gas, liquid, slurry, and/or solid waste streams can be converted into usable or even salable products while residual emissions are reduced to an absolute minimum. In applications for treatment of hazardous and radioactive waste streams, the PERC system could be used for destruction of the hazardous organic constituents and/or significant waste volume reduction while capturing the radioactive fraction in a non-leachable form. Like Direct Current (DC) and Alternating Current (AC) arc plasma systems, ICP torches offer sufficient energy to decompose, melt and/or vitrify any waste stream. The decision for an arc plasma or an IC plasma system has to be made on a case by case evaluation and is highly dependent on the specific waste stream's form and composition. Induction coupled plasma technology offers one simple, but significant difference compared to DC or AC arc plasma systems: the ICP torch is electrodeless. To date, enormous research effort has been spent to improve the lifetime of electrodes and the effectiveness of related cooling systems. Arc plasma systems are established in research laboratories worldwide and are approaching a broad use in commercial applications. ICP technology has been improved relatively recently, but nowadays offers complete new and beneficial approaches in the field of waste conversion and treatment

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.

What Intellectual Property Lawyers can learn from Barbra Streisand, Sepp Blatter, and the "Coca-Cola Cry-Baby": Dealing with "Trademark Bullying" in South Africa

OpenAIRE

André M Louw

2013-01-01

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 the...

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

Directory of Open Access Journals (Sweden)

Britta Stadelmann

2014-12-01

Full Text Available A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ, a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

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.

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

Intravenous contrast medium application in elderly patients - evaluation of Iopentol (Imagopaque trademark 300); Intravenoese Kontrastmittel-Applikation bei aelteren Patienten - Anwendungsbeobachtung von Iopentol (Imagopaque trademark 300)

Energy Technology Data Exchange (ETDEWEB)

Rathsmann, P.; Jacobs, G.F.; Mueller, R.D. [Zentrum fuer Klinische Radiologie, Kliniken Essen-Sued (Germany)

2004-12-01

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.)

Development of dispersion-strengthened XD (trademark) Cu alloys for high heat-flux applications

Science.gov (United States)

Kumar, K. Sharvan

1993-01-01

In a previous effort sponsored by NASA LeRC, the XD(trademark) process was used to produce ZrB2 particulate reinforcements in Cu and the resulting extruded material was microstructurally characterized and evaluated in tension over a range of temperatures. A problem that was encountered in that study was microstructural inhomogeneity resulting from the frequent presence of 'ZrB2 agglomerates' that were several microns in size. The presence of these agglomerates was attributed to improper mixing of powders in the green compact used in the XD process for elemental boron powder segregation. In this program, several milling parameters were examined in an effort to optimize this processing step; two levels of ZrB2 reinforcements were considered (7 vol. percent and 15 vol. percent). Microstructures of the reacted powder mass were examined to verify the absence of these agglomerates. Larger bathes of powder were then mixed, reacted, machined to size, canned, and extruded. The microstructure and tensile properties of these extrusions were examined, and the measured properties were correlated with the observed microstructure. Large unreacted or partially reacted Zr particles were present. These particles affected the mechanical properties deleteriously, and their presence is attributed to insufficient heat of reaction during XD synthesis. Alternate processing routes are recommended.

Savings estimates for the ENERGY STAR (registered trademark) voluntary labeling program: 2001 status report; TOPICAL

International Nuclear Information System (INIS)

Webber, Carrie A.; Brown, Richard E.; Mahajan, Akshay; Koomey, Jonathan G.

2002-01-01

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

Evaluation of iopentol (Imagopaque trademark 350) in CT enhancement. A multi-centre monitoring trial assessing adverse events and diagnostic information - results from 1823 patients in France

International Nuclear Information System (INIS)

Oxaal, M.; Lambrechts, M.; Bunouf, P.; Menuet, J.F.

1997-01-01

Objectives: To evaluate the safety and efficacy of iopentol 350 mg I/ml (Imagopaque trademark /Ivepaque trademark , Nycomed Imaging As, Oslo, Norway), a monomeric non-ionic contrast medium for computed tomography, in a large population. To identify predictive factors for patient safety. Materials and methods: One thousand eight hundred and twenty-three (1,823) patients form 48 centres in France were included during a 5-month period. Safety was evaluated by registering adverse events (AEs) reported by the patients, and data were analysed using a multiple factor model. Results: Only 2.6% of the patients experienced AEs other than discomfort. There were no serious AEs. Overall, AEs were more frequent in patients under 50 years of age, in women, and in patients who received contrast medium as a single bolus. Contrast enhancement was considered adequate or better in 98.9% of the patients. A large variation in discomfort (local warmth/chill or pain) frequency was seen between centres, ranging from 0% to 81%. This result implies that factors other than the CM influence the incidence of discomfort. Conclusions: This first study in a large population shows that iopentol 350 mg I/ml is well tolerated and provides CT images of excellent, good or adequate quality in the vast majority of patients. Age, sex and injection procedure were shown to be independent predictors in the AE survey. (orig.)

Successful kidney transplantation across a positive complement-dependent cytotoxicity crossmatch by using C1q assay-directed, bortezomib-assisted desensitization

Science.gov (United States)

Lee, Juhan; Park, Borae G.; Jeong, Hyang Sook; Park, Youn Hee; Kim, Sinyoung; Kim, Beom Seok; Kim, Hye Jin; Huh, Kyu Ha; Jeong, Hyeon Joo; Kim, Yu Seun

2017-01-01

Abstract Rationale: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies. Patient concerns: A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive. Diagnoses: Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay. Interventions: Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation. Outcomes: The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant. Lessons: The results of XM test and solid-phase assay should be interpreted in the context of the individual patient. PMID:28953652

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

Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

Directory of Open Access Journals (Sweden)

Dario Barbone

Full Text Available When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression

Science.gov (United States)

Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G.; Longley, Daniel B.; Bueno, Raphael; Sugarbaker, David J.; Fennell, Dean A.; Broaddus, V. Courtney

2012-01-01

When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies. PMID:23300762

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 ...

On Establishment of Trademarks on the Internet Policy%网络市场中的商标政策研究刘媛

Institute of Scientific and Technical Information of China (English)

刘媛

2013-01-01

The Internet has changed society structure deeply .In market econ-omy, online market has better self-control mechanism comparing with the tradition-al market .Its characteristics include more participants , stronger network externali-ty;more important role trademarks will play better externality , lower cost of busi-ness and infringement , and the changes of market failure .But new market failure still calls for the government intervention .Judicature can be included in it in a broad sense .So when establish the policy of trademarks on the internet , to let trademark’s function of adjusting market ’s efficiency do better , we should agree that“market first , government second”.%互联网深刻地改变着社会结构。市场经济中，网络市场呈现出比传统市场更为优良的自我调节机制。广泛的参与者，强大的网络外部性，商标作用增加，经营和侵权成本降低，市场失灵因素发生变化等都是它的突出特点。但是新的市场失灵仍然要求必要时政府进行干预，其中司法可以被纳入广义的政府干预之中。所以网络市场中的商标政策，应是“市场为主，政府为辅”，充分发挥商标的市场效率调节作用。

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.

Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after Autologous Stem Cell Transplantation for AL Amyloidosis.

Science.gov (United States)

Qamar, Hina; Lee, Adrienne; Valentine, Karen; Skeith, Leslie; Jimenez-Zepeda, Victor H

2017-01-01

Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

Directory of Open Access Journals (Sweden)

Victor H Jimenez-Zepeda

2017-05-01

Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

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

Successful kidney transplantation across a positive complement-dependent cytotoxicity crossmatch by using C1q assay-directed, bortezomib-assisted desensitization: A case report.

Science.gov (United States)

Lee, Juhan; Park, Borae G; Jeong, Hyang Sook; Park, Youn Hee; Kim, Sinyoung; Kim, Beom Seok; Kim, Hye Jin; Huh, Kyu Ha; Jeong, Hyeon Joo; Kim, Yu Seun

2017-09-01

Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies. A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive. Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay. Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation. The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant. The results of XM test and solid-phase assay should be interpreted in the context of the individual patient.

Positioning of the new trademark HEIN GAS in the liberalized gas market; Die Neupositionierung der Marke HEIN GAS im liberalisierten Gasmarkt

Energy Technology Data Exchange (ETDEWEB)

Unbehaun, C. [HEIN GAS Hamburger Gaswerke GmbH, Hamburg (Germany)

2000-10-01

Trademarks are getting increasingly important as a marketing factor in natural gas supply. The HEIN GAS company aims at becoming one of the top utilities in northern Germany. The contribution shows how marketing research and strategies are employed to achieve this. [German] Die kommunikativen Aktivitaeten aller Gasunternehmen werden zukuenftig einen entscheidenden Marktfaktor darstellen, um Geschaefts- und Privatkunden zu halten bzw. weitere zu gewinnen. Gerade im deutschen Gasmarkt, der durch austauschbare Produkte gekennzeichnet ist, kommt der Marke besondere Bedeutung zu. Der Preis ist zwar ein wichtiger, aber nicht immer allein entscheidendeer Wettbewerbsfaktor. Fuer das Unternehmen HEIN GAS heisst dies, auch im kommunikativen Wettbewerb zu bestehen. Es wird der Weg beschrieben, HEIN GAS zu einer Fuehrungsmarke im norddeutschen Waermemarkt zu etablieren. Dabei wird aufgezeigt, wie die Ergebnisse durch Marktforschung ueberprueft werden.

Monolithically interconnected Silicon-Film{trademark} module technology: Annual technical report, 25 November 1997--24 November 1998

Energy Technology Data Exchange (ETDEWEB)

Hall, R.B.; Ford, D.H.; Rand, J.A.; Ingram, A.E.

1999-11-11

AstroPower continued its development of an advanced thin-silicon-based photovoltaic module product. This module combines the performance advantages of thin, light-trapped silicon layers with the capability of integration into a low-cost, monolithically interconnected array. This report summarizes the work carried out over the first year of a three-year, cost-shared contract, which has yielded the following results: Development of a low-cost, insulating, ceramic substrate that provides mechanical support at silicon growth temperatures, is matched to the thermal expansion of silicon, provides the optical properties required for light trapping through random texturing, and can be formed in large areas on a continuous basis. Different deposition techniques have been investigated, and AstroPower has developed deposition processes for the back conductive layer, the p-type silicon layer, and the mechanical/chemical barrier layer. Polycrystalline films of silicon have been grown on ceramics using AstroPower's Silicon-Film{trademark} process. These films are from 50 to 75 {micro}m thick, with columnar grains extending through the thickness of the film. Aspect ratios from 5:1 to 20:1 have been observed in these films.

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.

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.)

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

Science.gov (United States)

Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

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.

Application of the biological forced air soil treatment (BIOFAST trademark) technology to diesel contaminated soil

International Nuclear Information System (INIS)

Lyons, K.A.; Leavitt, M.E.; Graves, D.A.; Stanish, S.M.

1993-01-01

A subsurface Biological Forced Air Soil Treatment (BIOFAST trademark) system was constructed at the Yellow Freight System, Inc. (Yellow Freight) New Haven facility in Connecticut as a means of expediting the remediation of soils impacted by a diesel fuel release. Prior to beginning construction activities the soils were evaluated for the feasibility of bioremediation based on soil characteristics including contaminant degrading bacteria, moisture content, and pH. Based on results of stimulant tests with oxygen and nutrients, the addition of fertilizer during the construction of the cell was recommended. Following the removal of underground storage tanks, the bioremediation cell was constructed by lining the enlarged excavation with high density polyethylene (HDPE) and backfilling alternating layers of nutrient-laden soil and pea gravel. Passive and active soil vapor extraction (SVE) piping was included in the gravel layers and connected to a blower and vapor treatment unit, operated intermittently to supply oxygen to the subsurface cell. Operating data have indicated that the bacteria are generating elevated levels of CO 2 , and the SVE unit is evacuating the accumulated CO 2 from the soils and replacing it with fresh air. These data suggest that the bioremediation process is active in the soils. Soil samples collected from within the soil pit subsequent to installation and again after 10 months of operation indicate that TPH concentrations have decreased by as much as 50%

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.

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.

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.

MCNPX{trademark} -- The LAHET{trademark}/MCNP{trademark} code merger

Energy Technology Data Exchange (ETDEWEB)

Hughes, H.G.; Adams, K.J.; Chadwick, M.B. [and others

1997-08-01

The MCNP code is written and maintained by Group X-TM at Los Alamos National Laboratory. In response to the demands of the accelerator community, the authors have undertaken a major effort to expand the capabilities of MCNP to increase the set of transportable particles; to make use of newly evaluated high-energy nuclear data tables for neutrons, protons, and potentially other particles; and to incorporate physics models for use where tabular data are unavailable. A preliminary version of the expanded code, called MCNPX, has now been issued for testing. The new code includes all existing LAHET physics modules, and has the ability to utilize the 150-MeV data libraries that have recently been released by LANL Group T-2.

Demonstration Of LEACHXS(trademark)/Orchestra Capabilities By Simulating Constituent Release From A Cementitious Waste Form In A Reinforced Concrete Vault

International Nuclear Information System (INIS)

Langton, C.; Meeussen, J.; Sloot, H.

2010-01-01

The objective of the work described in this report is to demonstrate the capabilities of the current version of LeachXS(trademark)/ORCHESTRA for simulating chemical behavior and constituent release processes in a range of applications that are relevant to the CBP. This report illustrates the use of LeachXS(trademark)/ORCHESTRA for the following applications: (1) Comparing model and experimental results for leaching tests for a range of cementitious materials including cement mortars, grout, stabilized waste, and concrete. The leaching test data includes liquid-solid partitioning as a function of pH and release rates based on laboratory column, monolith, and field testing. (2) Modeling chemical speciation of constituents in cementitious materials, including liquid-solid partitioning and release rates. (3) Evaluating uncertainty in model predictions based on uncertainty in underlying composition, thermodynamic, and transport characteristics. (4) Generating predominance diagrams to evaluate predicted chemical changes as a result of material aging using the example of exposure to atmospheric conditions. (5) Modeling coupled geochemical speciation and diffusion in a three layer system consisting of a layer of Saltstone, a concrete barrier, and a layer of soil in contact with air. The simulations show developing concentration fronts over a time period of 1000 years. (6) Modeling sulfate attack and cracking due to ettringite formation. A detailed example for this case is provided in a separate article by the authors (Sarkar et al. 2010). Finally, based on the computed results, the sensitive input parameters for this type of modeling are identified and discussed. The chemical speciation behavior of substances is calculated for a batch system and also in combination with transport and within a three layer system. This includes release from a barrier to the surrounding soil as a function of time. As input for the simulations, the physical and chemical properties of the

The interpretation practice of The European Court of Justice while judging the conflict between labelling applied as trademark with elderly right of another person

Directory of Open Access Journals (Sweden)

Hana Kelblová

2010-01-01

Full Text Available The article deals with the verification of the starting hypothesis of complementariness of the law of consumer protection and the law of intellectual property. In order to achieve that goal the author analyzes individual the Czech Trade Marks Act from the standpoint of protection of rights and interests of consumers.The article follows the categorical requirement of a public law rule, the Consumer Protection Act, which prohibits deceiving consumers and establishes that deceiving may also consist in offering products and services unjustified designated by misleading trade mark.The consumer is deceived most frequently when trade marks are used for designation of products and their promotion. The Trade Marks Act may be analyzed in relation to consumer protection first from the standpoint of consumer protection against trade marks misleading someone about the origin and quality of products and services designated by them. Then it is possible to examine the question whether requirements of a designation for being registered as a trade mark are at the same time those attributes of the trade mark which meet the declared intention of the lawmaker, i.e. that the trade mark should be a source of information for the consumer about the origin and quality of the product de­sig­na­ted by it.Especially, the article deals with an interpretation of the conception „Likelihood of Confusion“ as the fundamental conception while judging the conflict with elderly trademarks applying for the re­gi­stra­tion into the list of The Patent Office.A perception of an average consumer is a fundamental factor for a judgement of „Likelihood of Confusion“ as results from the decision practice of The Czech Patent Office, Czech courts and The European Court of Justice. This is proof of the conclusion that rules of the Trademark Law are rules of the Consumer protection Law.

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

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.

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

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

CCR 20th anniversary commentary: In the beginning, there was PS-341.

Science.gov (United States)

Teicher, Beverly A; Anderson, Kenneth C

2015-03-01

Proteasome inhibitors have a 20-year history in cancer therapy. The first proteasome inhibitor, bortezomib, a breakthrough treatment for multiple myeloma, moved rapidly through development from the bench in 1994 to first FDA approval in 2003. Clinical Cancer Research has chronicled the development of proteasome inhibitors with publication of reports on bortezomib, carfilzomib, and the oral proteasome inhibitor ixazomib (MLN9708). ©2015 American Association for Cancer Research.

Friction Stir Weld Inspection Through Conductivity Imaging Using Shaped Field MWM(Registered Trademark) - Arrays

Science.gov (United States)

Goldfine, Neil; Grundy, David; Zilberstein, Vladimir; Kinchen, David G.; McCool, Alex (Technical Monitor)

2002-01-01

Friction Stir Welds (FSW) of Al 2195-T8 and Al 2219-T8, provided by Lockheed Martin Michoud Operations, were inspected for lack-of-penetration (LOP) defects using a custom designed MWM-Array, a multi-element eddy-current sensor. MWM (registered trademark) electrical conductivity mapping demonstrated high sensitivity to LOP as small as 0.75 mm (0.03 in.), as confirmed by metallographic data that characterized the extent of LOP defects. High sensitivity and high spatial resolution was achieved via a 37-element custom designed MWM-Array allowing LOP detection using the normalized longitudinal component of the MWM measured conductivity. This permitted both LOP detection and correlation of MWM conductivity features with the LOP defect size, as changes in conductivity were apparently associated with metallurgical features within the near-surface layer of the LOP defect zone. MWM conductivity mapping reveals information similar to macro-etching as the MWM-Array is sensitive to small changes in conductivity due to changes in microstructure associated with material thermal processing, in this case welding. The electrical conductivity measured on the root side of FSWs varies across the weld due to microstructural differences introduced by the FSW process, as well as those caused by planar flaws. Weld metal, i.e., dynamically recrystallized zone (DXZ), thermomechanically affected zone (TMZ), heat-affected zone (HAZ), and parent metal (PM) are all evident in the conductivity maps. While prior efforts had met with limited success for NDE (Nondestructive Evaluation) of dissimilar alloy, Al2219 to Al2195 FSW, the new custom designed multi-element MWM-Array achieved detection of all LOP defects even in dissimilar metal welds.

Molecular mechanisms for synergistic effect of proteasome inhibitors with platinum-based therapy in solid tumors.

Science.gov (United States)

Chao, Angel; Wang, Tzu-Hao

2016-02-01

The successful development of the proteasome inhibitor bortezomib as an anticancer drug has improved survival in patients with multiple myeloma. With the emergence of the newly US Food and Drug Administration-approved proteasome inhibitor carfilzomib, ongoing trials are investigating this compound and other proteasome inhibitors either alone or in combination with other chemotherapy drugs. However, in solid tumors, the efficacy of proteasome inhibitors has not lived up to expectations. Results regarding the potential clinical efficacy of bortezomib combined with other agents in the treatment of solid tumors are eagerly awaited. Recent identification of the molecular mechanisms (involving apoptosis and autophagy) by which bortezomib and cisplatin can overcome chemotherapy resistance and sensitize tumor cells to anticancer therapy can provide insights into the development of novel therapeutic strategies for patients with solid malignancies. Copyright © 2016. Published by Elsevier B.V.

Resolution of thermal-hydraulic safety and licensing issues for the system 80+trademark design

International Nuclear Information System (INIS)

Carpentino, S.E.; Ritterbusch, S.E.; Schneider, R.E.

1995-01-01

The System 80+ 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

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

Science.gov (United States)

Usmani, S Z; Cavenagh, J D; Belch, A R; Hulin, C; Basu, S; White, D; Nooka, A; Ervin-Haynes, A; Yiu, W; Nagarwala, Y; Berger, A; Pelligra, C G; Guo, S; Binder, G; Gibson, C J; Facon, T

2016-01-01

To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio

Production of strontium-82 for the Cardiogen trademark PET generator: a project of the Department of Energy Virtual Isotope Center

International Nuclear Information System (INIS)

Phillips, D.R.; Peterson, E.J.; Taylor, W.A.; Jamriska, D.J.; Hamilton, V.T.; Kitten, J.J.; Valdez, F.O.; Salazar, L.L.; Pitt, L.R.; Heaton, R.C.; Kolsky, K.L.; Mausner, L.F.; Kurczak, S.; Zhuikov, B.L.; Kokhanyuk, V.M.; Konyakhin, N.A.; Nortier, F.M.; Walt, T.N. van der; Hanekom, J.; Sosnowski, K.M.; Carty, J.S.

2000-01-01

In December of 1989, the United States Food and Drug Administration approved 82 Rb chloride in saline solution for cardiological perfusion imaging by positron emission tomography (PET). The solution is derived from a 82 Sr generator system that is presently manufactured by Bristol Myers Squibb and distributed for clinical application in the United States by Bracco Diagnostics, Inc. Many years of research and development by people in several institutions led up to the approval for clinical use. Currently, there are about 15 sites in the U.S. that perform clinical myocardial perfusion imaging by PET using 82 Rb chloride from the generator. In order to manufacture the generators, Bristol Myers Squibb requires about 1600 mCi of 82 Sr every 30 days. The United States Department of Energy and MDS Nordion, Canada are the current suppliers with qualified Drug Master Files for the production and distribution of this nuclide for the Cardiogen trademark generator. These two entities have worked together over the years to assure the regular, reliable supply of the 82 Sr. Here we describe the facilities and methods used by the Department of Energy in its Virtual Isotope Center to make and distribute the nuclide. (orig.)

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.

Engineering and innovative erection concept for the containment liner for an EPR trademark

International Nuclear Information System (INIS)

Goehring, Rainer

2010-01-01

The determination of the optimal design of the containment liner considering amount of material, manufacturing and erection was the challenge for the engineering team of Babcock Noell GmbH. The construction costs of a Nuclear Power Plant are also impacted by the erection time of components. Therefore, it is necessary to optimize the erection times and consequently essentially to shorten. One possibility has been demonstrated by Babcock Noell GmbH with the erection concept of a containment liner. The liner is preassembled on the pre-assembly place in rings of up to 12 meter height, with the nominal diameter of 47 meter and a weight of approximately up to 200 tonnes. These rings, as well as the containment cup and the dome, are lifted with a heavy load crane into the reactor building. Several load cases for normal operation and accidental conditions as well as severe accidents have been analysed. The special load cases in the vicinity of penetrations and anchor plates have been calculated. The results of theses analyses have been considered in the actual design of the liner. This is the topic of the speech '' Computational Concept for the Containment Liner for EPR trademark '', given by Mr. Franz Nagelstutz, Abt. Planning, Babcock Noell GmbH und Mr. Nils Anders, Babcock Noell GmbH, Abt. Planning. With this concept, the construction activities on the inner containment wall are only five times disrupted by the welding and coating of the circumferential weld (approx. 25 calendar days). In comparison with the common known erection concept of welding of liner shells in situ, at least 20 weeks are saved on the schedule. An integrated concept from planning, manufacturing and erection of this large component has been implemented. It could be demonstrated that within the given time frame, with the required quality and within the required tolerances the containment liner for the Nuclear Power Plant can be delivered to the Client. (orig.)

Development of a new neutron shielding material, TN trademark Resin Vyal for transport/storage casks for radioactive materials

Energy Technology Data Exchange (ETDEWEB)

Abadie, P. [COGEMA Logistics (AREVA Group), Saint-Quentin-en-Yvelines (France)

2004-07-01

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{sup 22} at/cm{sup 3} for hydrogen and 9.10{sup 20} at/cm{sup 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.

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

Sequence analysis of laci mutations obtained from lung cells of radon-exposed big blue trademark transgenic mice

International Nuclear Information System (INIS)

Layton, A.D.; Cross, F.T.; Steigler, G.L.; Stillwell, L.S.; Jostes, R.F.; Lutze, L.H.

1994-01-01

We have exposed Big Blue trademark transgenic mice by inhalation to 320, 640 and 960 Working Level Months (WLM) of radon progeny. Mice were sacrificed after 3, 6 and 9 days; the time periods required to obtain the exposures. Control mice were also sacrificed at each time interval. In each case all tissues were excised, flash frozen in liquid nitrogen, and stored at -80 degrees C for further analysis. Twelve lacI mutations have been isolated from the lung tissue of a mouse from the 960-WLM exposure group; the lacI genes from these mutants have been sequenced. Sequence data indicate that three of the mutants have a C;G deletion at BP 978 and are possibly clonal in origin. Two mutants have multiple events within the gene: one has a an A:T to C:G transversion and a C:G insertion separated by 291 BPs; the second has a G:C to A:T transition as well as an A:T deletion followed by 6 base pairs downstream by a T:A insertion. Other mutations include a single G:C to A:T transition, a two base pair deletion, and a C:G to T:A transition. Mutant plaques are being evaluated from individual mice at other dose levels. Time course experiments are also planned. These studies will help define the molecular fine structure of mutations induced by high-LET radiation exposure

The European Medicines Agency Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

Science.gov (United States)

Tzogani, Kyriaki; van Hennik, Paula; Walsh, Ita; De Graeff, Pieter; Folin, Annika; Sjöberg, Jan; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

2017-11-30

On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3-4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3-4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7

Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.

Science.gov (United States)

Raje, Noopur S; Moreau, Philippe; Terpos, Evangelos; Benboubker, Lotfi; Grząśko, Norbert; Holstein, Sarah A; Oriol, Albert; Huang, Shang-Yi; Beksac, Meral; Kuliczkowski, Kazimierz; Tai, Datchen F; Wooldridge, James E; Conti, Ilaria; Kaiser, Christopher J; Nguyen, Tuan S; Cronier, Damien M; Palumbo, Antonio

2017-03-01

In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m 2 on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

KRITERIA UNSUR MILIK UMUM DALAM PENDAFTARAN MEREK BERDASARKAN PASAL 5 HURUF C UNDANG-UNDANG NOMOR 15 TAHUN 2001 TENTANG MEREK

OpenAIRE

SILVIYA, RINI

2016-01-01

Trademark has a very important role because trademark differentiate goods or services which traded in the market. Absolute requirement for trademark registration is that the trademark should have a differentiating factor. Article 5 letter (c) Law No. 15 of 2001 about Trademark regulate that a trademark could not be registered if which trademark has belongs to public. Article 5 letter (c) Law No. 15 of 2001 about Trademark explanation did not explain the meaning and the criteria belongs to pub...

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.

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.

An electrochemical method for on-line monitoring of biofilm activity in cooling water using the BIoGEORGE trademark probe

International Nuclear Information System (INIS)

Licina, G.J.; Nekoksa, G.; Howard, R.L.

1994-01-01

The presence of active microorganisms on piping and components in cooling water systems can have a profound effect on the corrosion performance of such systems. Microbiologically influenced corrosion (MIC) can result in premature failures of critical and support systems, increased downtime of equipment for repairs and maintenance, and increased operating costs associated with mitigation measures. In some cases, MIC has forced premature replacement of tanks, heat exchangers, and piping systems with a severe effect on plant availability. Monitoring methods that alert plant operators that biofilm formation is occurring on pipe work and components permit the operators to initiate mitigation actions before biofouling becomes severe or MIC has occurred. An electrochemical probe to permit on-line monitoring of biofilm activity under power plant or other industrial exposure conditions is under development. This device, the BIoGEORGE trademark electrochemical biofilm monitor, permits on-line evaluations of the effects of biofilm formation upon the surfaces of passive alloys such as stainless steels exposed to cooling water environments. Benchtop experiments have shown that biofilm formation on stainless steel surfaces can be detected by an electrochemical indication well in advance of any visual evidence of biofilm or corrosion on the electrodes. The design of the probe, results of benchtop experiments, and a description of its installation at the Browns Ferry Nuclear Plant are described

Treatment of acidic mine waters from the Solbec-Cupra site using the Mediaflex{trademark} process; Traitement des eaux minieres acides du site Solbec-Cupra par le procede Mediaflex{sub TM}

Energy Technology Data Exchange (ETDEWEB)

Belanger, M -C; Ross, A; Shoiry, J [Valoraction Inc., Sherbrooke, PQ (Canada)

1995-01-01

Applications and development of Mediaflex{trademark} filter treatment technology are described. The method combines physical, chemical, and biological processes into a technology suitable for purification of sanitary landfill leachates, septic tank sludge, and acidic mine waters. More than a dozen of the patented filters are in use. The treatment can reach 99.9% removal of heavy metals and phenolic compounds present in waste water. Since installation of the Mediaflex{sub TM} filter at the Cambior Solbec-Cupra mining site more than 50,000 cubic metres of acidic mine waste waters (pH 5.5) have been treated. After Mediaflex{sub TM} filtration, the pH is approximately 8.0, with the heavy metal content reduced substantially. 3 refs., 4 figs., 3 tabs.

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.)

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

International Nuclear Information System (INIS)

Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

2015-01-01

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

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

Selective removal/recovery of RCRA metals from waste and process solutions using polymer filtration trademark technology

International Nuclear Information System (INIS)

Smith, B.F.

1997-01-01

Resource Conservation and Recovery Act (RCRA) metals are found in a number of process and waste streams at many DOE, U.S. Department of Defense, and industrial facilities. RCRA metals consist principally of chromium, mercury, cadmium, lead, and silver. Arsenic and selenium, which form oxyanions, are also considered RCRA elements. Discharge limits for each of these metals are based on toxicity and dictated by state and federal regulations (e.g., drinking water, RCRA, etc.). RCRA metals are used in many current operations, are generated in decontamination and decommissioning (D ampersand D) operations, and are also present in old process wastes that require treatment and stabilization. These metals can exist in solutions, as part of sludges, or as contaminants on soils or solid surfaces, as individual metals or as mixtures with other metals, mixtures with radioactive metals such as actinides (defined as mixed waste), or as mixtures with a variety of inert metals such as calcium and sodium. The authors have successfully completed a preliminary proof-of-principle evaluation of Polymer Filtration trademark (PF) technology for the dissolution of metallic mercury and have also shown that they can remove and concentrate RCRA metals from dilute solutions for a variety of aqueous solution types using PF technology. Another application successfully demonstrated is the dilute metal removal of americium and plutonium from process streams. This application was used to remove the total alpha contamination to below 30 pCi/L for the wastewater treatment plant at TA-50 at Los Alamos National Laboratory (LANL) and from nitric acid distillate in the acid recovery process at TA-55, the Plutonium Facility at LANL (ESP-CP TTP AL16C322). This project will develop and optimize the PF technology for specific DOE process streams containing RCRA metals and coordinate it with the needs of the commercial sector to ensure that technology transfer occurs

Selective removal/recovery of RCRA metals from waste and process solutions using polymer filtration{trademark} technology

Energy Technology Data Exchange (ETDEWEB)

Smith, B.F. [Los Alamos National Lab., NM (United States)

1997-10-01

Resource Conservation and Recovery Act (RCRA) metals are found in a number of process and waste streams at many DOE, U.S. Department of Defense, and industrial facilities. RCRA metals consist principally of chromium, mercury, cadmium, lead, and silver. Arsenic and selenium, which form oxyanions, are also considered RCRA elements. Discharge limits for each of these metals are based on toxicity and dictated by state and federal regulations (e.g., drinking water, RCRA, etc.). RCRA metals are used in many current operations, are generated in decontamination and decommissioning (D&D) operations, and are also present in old process wastes that require treatment and stabilization. These metals can exist in solutions, as part of sludges, or as contaminants on soils or solid surfaces, as individual metals or as mixtures with other metals, mixtures with radioactive metals such as actinides (defined as mixed waste), or as mixtures with a variety of inert metals such as calcium and sodium. The authors have successfully completed a preliminary proof-of-principle evaluation of Polymer Filtration{trademark} (PF) technology for the dissolution of metallic mercury and have also shown that they can remove and concentrate RCRA metals from dilute solutions for a variety of aqueous solution types using PF technology. Another application successfully demonstrated is the dilute metal removal of americium and plutonium from process streams. This application was used to remove the total alpha contamination to below 30 pCi/L for the wastewater treatment plant at TA-50 at Los Alamos National Laboratory (LANL) and from nitric acid distillate in the acid recovery process at TA-55, the Plutonium Facility at LANL (ESP-CP TTP AL16C322). This project will develop and optimize the PF technology for specific DOE process streams containing RCRA metals and coordinate it with the needs of the commercial sector to ensure that technology transfer occurs.

Neregistruoto prekės ženklo gynimas

OpenAIRE

Granickas, Vaidotas

2006-01-01

Summary Universal globalization is best of all reflected by trademark spread. Trademarks are autonomous objects of agreements. Unregistered trademarks are characterized with high integrity as object of economic turnover; they quite easily spread over the boundaries of state jurisdiction. Unregistered trademark can not be protected by common legal means used in cases of registered trademarks. The fact that trademark is unregistered creates specificity in its protection, as parties are...

Prospective iterative trial of proteasome inhibitor-based desensitization.

Science.gov (United States)

Woodle, E S; Shields, A R; Ejaz, N S; Sadaka, B; Girnita, A; Walsh, R C; Alloway, R R; Brailey, P; Cardi, M A; Abu Jawdeh, B G; Roy-Chaudhury, P; Govil, A; Mogilishetty, G

2015-01-01

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

論美國關鍵字商標初始興趣混淆的民事責任與我國的議題現況評析──以網路搜尋引擎業者與資訊儲存服務提供者為中心 Civil Liability for Trademark Initial Interest Confusion to Keywords in US and Current Evaluation in Taiwan —Centering on Search Engine and Information Storage Service Provider

Directory of Open Access Journals (Sweden)

程法彰 Fa-Chang Cheng

2016-06-01

Full Text Available 網路搜尋引擎業者強大的資訊蒐集能力與網路資訊儲存業者強大的資訊儲存能力，引起商標權人對初始興趣混淆議題的高度重視。本文認為美國在實務案件中出現對網路搜尋引擎業者或資訊儲存服務提供者關鍵字搜尋的商標運用行為，過度解讀為直接侵權行為。這樣的作法不但破壞了侵權行為的理論基礎，亦不當的平衡商標權人的保護與網路發展的重要性。若我國將來採取與美國相同的基調，經由美國的相關經驗，對網路搜尋引擎業者或資訊儲存服務業關於關鍵字商標初始興趣混淆責任，亦應以間接侵權行為責任相繩。在責任的具體規範上，第一步或許可以藉由通過目前電子通訊傳播法草案，對於業者宣示最低的行為準則。最終本文建議經由草案中避風港條款機制，對於商標間接侵權行為的免責實踐經驗，並參考美國對於智慧財產間接侵權行為的規範，在我國商標法中增列間接侵權行為責任條文。 The enormous data collection power in search engine providers and the tremendous data storage power in information storage service providers arouse strong concerns about initial interest confusion to trademark use among the trademark owners. This article indicates that US judicial practice overreads the trademark use to keyword search mechanism in search engine providers and storage service providers as direct trademark infringement. This phenomenon not only tears down the fundamental torts theory but also strikes the inappropriate balance between the protection of trademark owners and the importance of Internet development. This article concludes that the indirect torts liability would be the most appropriate solution to resolve the trademark dispute for keywords initial confusion regarding search engine and information storage service if Taiwan follows the US experience. To get through the

Effectiveness of Sealed Double-Ring Infiltrometers trademark and effects of changes in atmospheric pressure on hydraulic conductivity

International Nuclear Information System (INIS)

McMullin, S.R.

1994-01-01

The Savannah River Site is currently evaluating some 40 hazardous and radioactive-waste sites for remediation. Among the remedial alternatives considered is closure using a kaolin clay cap. The hydraulic conductivity suggested by the US Environmental Protection Agency is 1.0 x 10 -7 cm/sec. One instrument to measure this value is the Sealed Double-Ring Infiltrometer trademark (SDRI). Six SDRI were recently installed on a kaolin test cap. Test results demonstrated uniform performance of these instruments. However, the test data showed as much as an order of magnitude of variation over time. This variation is attributed to both internal structural heterogeneity and variable external boundary conditions. The internal heterogeneity is caused by construction variability within a specified range of moisture and density. The external influences considered are temperature and barometric pressure. Temperature was discharged as a source of heterogeneity because of a lack of correlation with test data and a negligible impact from the range of variability. However, a direct correlation was found between changes in barometric pressure and hydraulic conductivity. This correlation is most pronounced when pressure changes occur over a short period of time. Additionally, this correlation is related to a single soil layer. When the wetting front passes into a more porous foundation layer, the correlation with pressure changes disappears. Conclusions are that the SDRI performs adequately, with good repeatability of results. The duration of test is critical to assure a statistically valid data set. Data spikes resulting from pressure changes should be identified, and professional judgment used to determine the representative hydraulic conductivity. Further evaluation is recommended to determine the impact of pressure change on the actual hydraulic conductivity

The application of zonal trademark combustion monitoring and tuning system to coal boilers for efficiency improvement and emissions reduction

Energy Technology Data Exchange (ETDEWEB)

Xu, Guang; Zhou, Wei; Widmer, Neil C.; Moyeda, David K. [GE Energy, Irvine, CA (United States)

2013-07-01

Coal-fired boilers equipped with Low NO{sub x} Burner (LNB) and Overfire Air (OFA) are challenged with maintaining good combustion conditions. In many cases, the significant increases in carbon monoxide (CO) and unburned carbon levels can be attributed to local poor combustion conditions as a result of poorly controlled fuel-air distribution within the furnace. The Zonal trademark combustion monitoring and tuning system developed by GE is available to detect and correct the furnace air-fuel distribution imbalance. The system monitors the boiler excess oxygen (O{sub 2}) and combustible gases, primarily carbon monoxide (CO), by using spatially distributed multipoint sensors located in the boiler's high temperature upper convective backpass region. At these locations, the furnace flow is still significantly stratified allowing tracing of poor combustion zones to specific burners and OFA ports. Using a model-based tuning system, operators can rapidly respond to poor combustion conditions by redistributing airflows to select burners and OFA ports. By improving combustion at every point within the furnace, the boiler can operate at reduced excess O{sub 2} and reduced furnace exit gas temperature (FEGT) while also reducing localized hot spots, corrosive gas conditions, slag formation, and carbon-in-ash. Benefits include improving efficiency, reducing NO{sub X} emissions, increasing output and maximizing availability. This chapter presents the results from implementing the Zonal combustion monitoring and tuning system on a 460 MW tangential-fired coal boiler in the Western United States.

Sequence analysis of LACI mutations obtained from lung cells of control and radon-exposed Big Blue trademark transgenic mice

International Nuclear Information System (INIS)

Jostes, R.F.; Cross, F.T.; Stillwell, L.

1995-01-01

We have exposed Stratagene Big Blue trademark transgenic mice by inhalation to 310, 640 and 960 Working Level Months (WLM) of radon progency. Twelve LacI mutations have been isolated from the lung tissue of a mouse from the 960-WLM group and the LacI gene sequenced. Mutations are scored only if they occur unambiguously in both strands of the mutant gene; the entire gene is evaluated. In addition, sixteen LacI mutations were isolated from the lung tissue of a mouse from the 640-WLM group; seven have been completely sequenced. Nine LacI mutations from the lung tissue of unirradiated control mice have been sequenced. Sequence data from the unirradiated mice are similar to that found in lung tissue at Stratagene; predominately G:C to A:T transitions in the protein associated region. The mutation spectrum from radon-irradiated mice is markedly different from that obtained with the control, unirradiated mice. Small deletions and insertions compromise 53% of the mutations in the irradiated mice. No multiple events have been noted in the spontaneous mutations; six of the mutations obtained from radon-irradiated mice (26%) have multiple events within the gene. In some, deletions, insertions are base changes occur together. The mutational events in the irradiated mice are approximately equally distributed throughout the gene. The breakpoint rejoining regions of large deletions obtained from the radon-irradiated mice are being studied at the University of California, San Francisco

PENGHAPUSAN PENDAFTARAN MEREK BERDASARKAN GUGATAN PIHAK KETIGA

Directory of Open Access Journals (Sweden)

Agus Mardianto

2010-01-01

Full Text Available The right of a trademark is an exclusive right granted by government. A registered trademark can be cancelled from the General List of Trademark. Cancellation of registration of a trademark can be claimed by a third party through a dispute to a Commercial Court based on article 61 paragraph (2 letter b of Trademark Law 2001. This research is aimed at studying the use of article 61 paragraph (2 letter b of Trademark Law 2001 as the base of dispute for cancelation of the registration of a trademark by a third party, and studying the legal consequences of a trademark cancelation. A qualitative juridicial normative method with descriptive analyses approaches was used to analyze secondary data derived from documents of decisions of Commercial Court of Central Jakarta Number 06/Merek/205/PN.Niaga.JKT.PST and documents of decisions of Supreme Court of the Republic of Indonesia Number 031K/N/HaKI2005. The result of the research showed that the application of article 61 paragraph (2 letter b of Trademark Law 2001 for the base of decision of the judges of Commercial Court of Central Jakarta was inappropritate. In judging at the use of a trademark, the judges only looked at the inconsistency of writtting styles or fonts or colours, but not taking into considerations of the purpose and intention of the parties that claimed the dispute. Cancelation of regitration of a trademark based on the dispute of a third party automatically resulted in the termination of legal protection of the related trademark. Keywords: trademark, cancelation of a trademark, third party, good intention, Commercial Court

Treatment of the femoropopliteal arteries with a novel rotational atherectomy system: early single-center experience with the Pathway PV trademark Atherectomy System; Behandlung von Laesionen der femoropoplitealen Arterien mittels eines neuartigen Rotationsatherektomiesystems: Erste single-center Erfahrungen mit dem Pathway PV trademark Atherectomy System

Energy Technology Data Exchange (ETDEWEB)

Wissgott, C.; Kamusella, P.; Richter, A.; Steinkamp, H.J. [Radiologie, DRK-Kliniken Berlin (Germany); Schink, T. [Institut fuer Biometrie, Charite Berlin (Germany); Klein-Weigel, P. [Angiologie, DRK-Kliniken Berlin (Germany)

2008-09-15

Purpose: The main problem when treating the superficial femoral and popliteal artery with PTA or stent implantation is the relatively high restenosis rate. Several ablative systems are available as an alternative. The purpose of this prospective study was to evaluate the safety and performance of a novel rotational and aspirating atherectomy system. Materials and Methods: From June to December 2006, we treated 23 patients, median age 70.3 years (58 - 91), with the rotational atherectomy system. All patients had de-novo lesions of the SFA or PA with a minimum stenosis of 70%. According to the Rutherford classification, 39% of the patients were in category 2 and 61% in category 3. The median lesion length was 26.3 mm (5 - 100 mm). 26% of the patients had occlusions. Results: The technical success rate was 100%. In 14 cases (61%) additional balloon dilatation was applied, in two cases stent implantation were performed. The median treatment duration with the device was 187.7 {+-} 106.1 s (59 - 391 s). The aspirated volume was 116.5 {+-} 72.0 ml. The ankle brachial index improved from preinterventional 0.60 {+-} 0.16 to postinterventional 0.85 {+-} 0.13 and after 6 month 0.80 {+-} 0.13. During follow-up, two (8%) restenosis occurred. There were two complications, one dissection and one distal embolization. Follow-up could not be performed for two patients (8%). Conclusion: Atherectomy of femoropopliteal lesions with the Pathway PV trademark Atherectomy System is very safe and effective. The low restenosis rate of 8% is promising, but there is still a lack of long-term results.

77 FR 58528 - Performance Review Board (PRB)

Science.gov (United States)

2012-09-21

.... Frederick W. Steckler, Chief Administrative Officer, United States Patent and Trademark Office. Margaret A..., Commissioner for Trademarks, United States Patent and Trademark Office. Anthony P. Scardino, Chief Financial Officer, United States Patent and Trademark Office. John B. Owens II, Chief Information Officer, United...

76 FR 64076 - Performance Review Board (PRB)

Science.gov (United States)

2011-10-17

..., Chief Financial Officer, United States Patent and Trademark Office. John B. Owens II, Chief Information Officer, United States Patent and Trademark Office. Bernard J. Knight Jr., General Counsel, United States... Trademark Office. Patricia M. Richter, Chief Administrative Officer, United States Patent and Trademark...

75 FR 63147 - Performance Review Board (PRB)

Science.gov (United States)

2010-10-14

.... Patricia M. Richter, Chief Administrative Officer, United States Patent and Trademark Office. Robert L..., Commissioner for Trademarks, United States Patent and Trademark Office. Anthony P. Scardino, Chief Financial Officer, United States Patent and Trademark Office. John B. Owens II, Chief Information Officer, United...

78 FR 59658 - Performance Review Board

Science.gov (United States)

2013-09-27

... for Trademarks, United States Patent and Trademark Office Anthony P. Scardino, Chief Financial Officer, United States Patent and Trademark Office John B. Owens II, Chief Information Officer, United States.... Steckler, Vice Chair, Chief Administrative Officer, United States Patent and Trademark Office Margaret A...

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

PENGHAPUSAN PENDAFTARAN MEREK BERDASARKAN GUGATAN PIHAK KETIGA

Directory of Open Access Journals (Sweden)

Agus Mardianto

2010-01-01

Full Text Available The right of a trademark is an exclusive right granted by government. A registered trademark can be cancelled from the General List of Trademark. Cancellation of registration of a trademark can be claimed by a third party through a dispute to a Commercial Court based on article 61 paragraph (2 letter b of Trademark Law 2001. This research is aimed at studying the use of article 61 paragraph (2 letter b of Trademark Law 2001 as the base of dispute for cancelation of the registration of a trademark by a third party, and studying the legal consequences of a trademark cancelation. A qualitative juridicial normative method with descriptive analyses approaches was used to analyze secondary data derived from documents of decisions of Commercial Court of Central Jakarta Number 06/Merek/205/PN.Niaga.JKT.PST and documents of decisions of Supreme Court of the Republic of Indonesia Number 031K/N/HaKI2005. The result of the research showed that the application of article 61 paragraph (2 letter b of Trademark Law 2001 for the base of decision of the judges of Commercial Court of Central Jakarta was inappropritate. In judging at the use of a trademark, the judges only looked at the inconsistency of writtting styles or fonts or colours, but not taking into considerations of the purpose and intention of the parties that claimed the dispute. Cancelation of regitration of a trademark based on the dispute of a third party automatically resulted in the termination of legal protection of the related trademark.

Intellectual property arguments in tobacco industry legal challenges: lessons from recently concluded cases

Directory of Open Access Journals (Sweden)

Suzanne Zhou

2018-03-01

A substantial body of jurisprudence now confirms that IP does not provide the scope of protection commonly claimed by the industry. Tobacco control practitioners faced with such arguments can be confident that they are unfounded. Country / measure / jurisdiction Australia - plain packaging (WTO dispute settlement system Australia - plain packaging (High Court of Australia Australia - plain packaging (investor-state arbitration Uruguay - restrictions on brand variants and 80% graphic health warnings (investor-state arbitration United Kingdom - standardised packaging (Court of Appeal of England and Wales IP issues Obligation to provide certain trademark protections under TRIPS Protection of trademark as property under constitution Expropriation of trademark as investment under treaty; fair and equitable treatment re treatment of trademarks Expropriation of trademark as investment under treaty; fair and equitable treatment re treatment of trademarks Obligation to provide certain trademark protections under TRIPS and EU law; protection of trademark as property under European and UK law Decided in favour of Pending, reportedly Australia Australia, 2012 Australia, 2015 (dismissed at jurisdictional stage Uruguay, 2016 United Kingdom, 2016 Positive right to use trademark? Pending, point conceded as 'no' by complainants No Not decided No No Public health justification Pending Not applicable Not decided Yes Yes [Recent cases raising trademark issues

37 CFR 1.167 - Examination.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Examination. 1.167 Section 1.167 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Examination. Applications may be submitted by the Patent and Trademark Office to the Department of Agriculture...

37 CFR 11.9 - Limited recognition in patent matters.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Limited recognition in patent matters. 11.9 Section 11.9 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND TRADEMARK OFFICE...

37 CFR 2.81 - Post publication.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Post publication. 2.81 Section 2.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Publication and Post Publication § 2.81 Post publication. (a...

15 CFR 280.313 - Recordal of additional insignia.

Science.gov (United States)

2010-01-01

... for recordal of its trademark for fasteners if the trademark is the subject of a duly filed application or is registered in the United States Patent and Trademark Office on the Principal Register. Upon recordal, either the alphanumeric designation or the trademark, or both, may be used as recorded insignias...

Canadian Collaboration - Letter of Interest

International Development Research Centre (IDRC) Digital Library (Canada)

Keith C

Windows is either a registered trademark or a trademark of Microsoft Corporation in the United States and/or other countries. Mac is a trademark of Apple Inc., registered in the United States and other countries. Linux is the registered trademark of Linus Torvalds in the U.S. and other countries.

37 CFR 11.18 - Signature and certificate for correspondence filed in the Office.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Signature and certificate for correspondence filed in the Office. 11.18 Section 11.18 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND TRADEMARK OFFICE Recognition...

37 CFR 11.2 - Director of the Office of Enrollment and Discipline.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Director of the Office of Enrollment and Discipline. 11.2 Section 11.2 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND TRADEMARK OFFICE General Provisions General...

37 CFR 10.64 - Avoiding acquisition of interest in litigation or proceeding before the Office.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Avoiding acquisition of interest in litigation or proceeding before the Office. 10.64 Section 10.64 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK OFFICE Patent and...

37 CFR 1.2 - Business to be transacted in writing.

Science.gov (United States)

2010-07-01

... Correspondence § 1.2 Business to be transacted in writing. All business with the Patent and Trademark Office... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Business to be transacted in writing. 1.2 Section 1.2 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE...

37 CFR 2.191 - Business to be transacted in writing.

Science.gov (United States)

2010-07-01

... Trademark Cases § 2.191 Business to be transacted in writing. All business with the Office should be... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Business to be transacted in writing. 2.191 Section 2.191 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE...

Computed tomography depiction of small pediatric vessels with model-based iterative reconstruction

Energy Technology Data Exchange (ETDEWEB)

Koc, Gonca; Courtier, Jesse L.; Phelps, Andrew; Marcovici, Peter A.; MacKenzie, John D. [UCSF Benioff Children' s Hospital, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

2014-07-15

Computed tomography (CT) is extremely important in characterizing blood vessel anatomy and vascular lesions in children. Recent advances in CT reconstruction technology hold promise for improved image quality and also reductions in radiation dose. This report evaluates potential improvements in image quality for the depiction of small pediatric vessels with model-based iterative reconstruction (Veo trademark), a technique developed to improve image quality and reduce noise. To evaluate Veo trademark as an improved method when compared to adaptive statistical iterative reconstruction (ASIR trademark) for the depiction of small vessels on pediatric CT. Seventeen patients (mean age: 3.4 years, range: 2 days to 10.0 years; 6 girls, 11 boys) underwent contrast-enhanced CT examinations of the chest and abdomen in this HIPAA compliant and institutional review board approved study. Raw data were reconstructed into separate image datasets using Veo trademark and ASIR trademark algorithms (GE Medical Systems, Milwaukee, WI). Four blinded radiologists subjectively evaluated image quality. The pulmonary, hepatic, splenic and renal arteries were evaluated for the length and number of branches depicted. Datasets were compared with parametric and non-parametric statistical tests. Readers stated a preference for Veo trademark over ASIR trademark images when subjectively evaluating image quality criteria for vessel definition, image noise and resolution of small anatomical structures. The mean image noise in the aorta and fat was significantly less for Veo trademark vs. ASIR trademark reconstructed images. Quantitative measurements of mean vessel lengths and number of branches vessels delineated were significantly different for Veo trademark and ASIR trademark images. Veo trademark consistently showed more of the vessel anatomy: longer vessel length and more branching vessels. When compared to the more established adaptive statistical iterative reconstruction algorithm, model

Computed tomography depiction of small pediatric vessels with model-based iterative reconstruction

International Nuclear Information System (INIS)

Koc, Gonca; Courtier, Jesse L.; Phelps, Andrew; Marcovici, Peter A.; MacKenzie, John D.

2014-01-01

Computed tomography (CT) is extremely important in characterizing blood vessel anatomy and vascular lesions in children. Recent advances in CT reconstruction technology hold promise for improved image quality and also reductions in radiation dose. This report evaluates potential improvements in image quality for the depiction of small pediatric vessels with model-based iterative reconstruction (Veo trademark), a technique developed to improve image quality and reduce noise. To evaluate Veo trademark as an improved method when compared to adaptive statistical iterative reconstruction (ASIR trademark) for the depiction of small vessels on pediatric CT. Seventeen patients (mean age: 3.4 years, range: 2 days to 10.0 years; 6 girls, 11 boys) underwent contrast-enhanced CT examinations of the chest and abdomen in this HIPAA compliant and institutional review board approved study. Raw data were reconstructed into separate image datasets using Veo trademark and ASIR trademark algorithms (GE Medical Systems, Milwaukee, WI). Four blinded radiologists subjectively evaluated image quality. The pulmonary, hepatic, splenic and renal arteries were evaluated for the length and number of branches depicted. Datasets were compared with parametric and non-parametric statistical tests. Readers stated a preference for Veo trademark over ASIR trademark images when subjectively evaluating image quality criteria for vessel definition, image noise and resolution of small anatomical structures. The mean image noise in the aorta and fat was significantly less for Veo trademark vs. ASIR trademark reconstructed images. Quantitative measurements of mean vessel lengths and number of branches vessels delineated were significantly different for Veo trademark and ASIR trademark images. Veo trademark consistently showed more of the vessel anatomy: longer vessel length and more branching vessels. When compared to the more established adaptive statistical iterative reconstruction algorithm, model

37 CFR 11.5 - Register of attorneys and agents in patent matters; practice before the Office.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Register of attorneys and agents in patent matters; practice before the Office. 11.5 Section 11.5 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND TRADEMARK OFFICE...

WHITE PAPER: DEMONSTRATION OF EQUIVALENCY OF CANE AND SOFTWOOD BASED CELOTEX FOR 9975 PACKAGING

International Nuclear Information System (INIS)

Varble, J

2007-01-01

Cane-based Celotex(trademark) has been used extensively in various DOE packages as a thermal insulator and impact absorber. Cane-based Celotex(trademark) for the 9975 was manufactured by Knight-Celotex Fiberboard at their Marrero Plant in Louisiana. However, Knight-Celotex Fiberboard shut down their Marrero Plant in early 2007 due to impacts from hurricane Katrina and other economic factors. Therefore, cane-based Celotex(trademark) is no longer available for use in the manufacture of new 9975 packages. Knight-Celotex Fiberboard has Celotex(trademark) manufacturing plants in Danville, VA and Sunbury, PA that use softwood and hardwood, respectively, as a raw material in the manufacturing of Celotex(trademark). The purpose of this White Paper is to demonstrate that softwood-based Celotex(trademark) from the Knight-Celotex Danville Plant has performance equivalent to cane-based Celotex(trademark) from the Knight-Celotex Marrero Plant for transportation in a 9975 package

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.

ISSUES ON ENFORCEABILITY OF FINAL DECISIONS OF EUROPEAN UNION INTELLECTUAL PROPERTY OFFICE REGARDING EUROPEAN TRADEMARKS ON FIXING THE AMOUNT OF COST IN ROMANIA

Directory of Open Access Journals (Sweden)

Sorin Eduard PAVEL

2018-05-01

Full Text Available The purpose of this paper is to analyse the enforceability in Romania of final decisions fixing the amount of costs related to European trademarks, issued by European Union Intellectual Property Office. According to art 110 (1 and (2 of EU Regulation 2017/10011 , such decisions are titles enforceable in any Member State and enforcement proceedings are governed by applicable national civil law of the Member State in territory of which the enforcement is carried out. Apparently, the enforcement of these decisions in Member States should be a formal procedure devoid of issues. Things may be complex having in view that each Member State is compelled by the art 110 (2 of the EU Regulation 2017/1001, to designate a national authority responsible with the verification of the authenticity of respective decisions. Precisely, what happens when a Member State "forgot" to designate such national authority? Can enforcement proceedings regarding these decisions in respective Member State, be effective? Romania does not designate the national authority prescribed under art. 110 (2 of EU Regulation 2017/1001, fact that generates, at least from theoretical perspective, issues on the enforcement of this kind of decisions. In a nutshell, if no such national authority has been designated, the procedure on verification of authenticity of these decisions cannot be fulfilled, meaning that enforcement proceedings may be deemed as failing to comply with the national law.

DEMONSTRATION OF EQUIVALENCY OF CANE AND SOFTWOOD BASED CELOTEX FOR MODEL 9975 SHIPPING PACKAGES

International Nuclear Information System (INIS)

Watkins, R; Jason Varble, J

2008-01-01

Cane-based Celotex(trademark) has been used extensively in various Department of Energy (DOE) packages as a thermal insulator and impact absorber. Cane-based Celotex(trademark) fiberboard was only manufactured by Knight-Celotex Fiberboard at their Marrero Plant in Louisiana. However, Knight-Celotex Fiberboard shut down their Marrero Plant in early 2007 due to impacts from hurricane Katrina and other economic factors. Therefore, cane-based Celotex(trademark) fiberboard is no longer available for use in the manufacture of new shipping packages requiring the material as a component. Current consolidation plans for the DOE Complex require the procurement of several thousand new Model 9975 shipping packages requiring cane-based Celotex(trademark) fiberboard. Therefore, an alternative to cane-based Celotex(trademark) fiberboard is needed. Knight-Celotex currently manufactures Celotex(trademark) fiberboard from other cellulosic materials, such as hardwood and softwood. A review of the relevant literature has shown that softwood-based Celotex(trademark) meets all parameters important to the Model 9975 shipping package

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

Validation of High Displacement Piezoelectric Actuator Finite Element Models

Science.gov (United States)

Taleghani, B. K.

2000-01-01

The paper presents the results obtained by using NASTRAN(Registered Trademark) and ANSYS(Regitered Trademark) finite element codes to predict doming of the THUNDER piezoelectric actuators during the manufacturing process and subsequent straining due to an applied input voltage. To effectively use such devices in engineering applications, modeling and characterization are essential. Length, width, dome height, and thickness are important parameters for users of such devices. Therefore, finite element models were used to assess the effects of these parameters. NASTRAN(Registered Trademark) and ANSYS(Registered Trademark) used different methods for modeling piezoelectric effects. In NASTRAN(Registered Trademark), a thermal analogy was used to represent voltage at nodes as equivalent temperatures, while ANSYS(Registered Trademark) processed the voltage directly using piezoelectric finite elements. The results of finite element models were validated by using the experimental results.

Prekių ženklo naudojimo reikalavimas : teorinės ir praktinės problemos.

OpenAIRE

Klimkevičiūtė, Danguolė

2014-01-01

The article deals with the topical and problematical issues, related to the one of the requirements for a trademark, i.e. trademark use requirement, as the condition for the maintenance of trademark registration. The first part of the article provides analysis of the main provisions anticipated in international European Union and national Lithuanian legal regulation related to the trademark use requirement. First of all, it is important to provide analysis of the relevant date, when the trade...

Varemærkeret

DEFF Research Database (Denmark)

Wallberg, Knud; Ravn, Mikael Francke

The 5. th edition of the annotaded trademarks and collective marks act. The book also deals with the EU trademark system, and the Madrid System for registration of trademarks and with the the interaction between trdemark law and related rights (unfair competition, copyright, geographical...

77 FR 9213 - Submission for OMB Review; Comment Request

Science.gov (United States)

2012-02-16

.... 41(i)(1) to maintain a Public Search Facility to provide patent and trademark collections for... DEPARTMENT OF COMMERCE United States Patent and Trademark Office Submission for OMB Review; Comment Request The United States Patent and Trademark Office (USPTO) will submit to the Office of...

37 CFR 1.14 - Patent applications preserved in confidence.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent applications preserved in confidence. 1.14 Section 1.14 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES General Provisions...

78 FR 31885 - Patent Term Extension

Science.gov (United States)

2013-05-28

... DEPARTMENT OF COMMERCE Patent and Trademark Office Patent Term Extension ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and Trademark Office (USPTO), as part of its... States Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450. Federal Rulemaking Portal...

78 FR 7759 - Patent Cooperation Treaty

Science.gov (United States)

2013-02-04

... DEPARTMENT OF COMMERCE Patent and Trademark Office Patent Cooperation Treaty ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and Trademark Office (USPTO), as part of its... States Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450. Federal Rulemaking Portal...

75 FR 20561 - Patent Term Extension

Science.gov (United States)

2010-04-20

... DEPARTMENT OF COMMERCE Patent and Trademark Office Patent Term Extension ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and Trademark Office (USPTO), as part of its... Officer, Office of the Chief Information Officer, United States Patent and Trademark Office, P.O. Box 1450...

37 CFR 1.215 - Patent application publication.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent application publication. 1.215 Section 1.215 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Publication...

37 CFR 1.98 - Content of information disclosure statement.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Content of information disclosure statement. 1.98 Section 1.98 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing...

37 CFR 1.97 - Filing of information disclosure statement.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Filing of information disclosure statement. 1.97 Section 1.97 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing...

37 CFR 1.9 - Definitions.

Science.gov (United States)

2010-07-01

... Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES General Provisions General Information and Correspondence § 1.9... Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark...

37 CFR 11.3 - Suspension of rules.

Science.gov (United States)

2010-07-01

... Section 11.3 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND TRADEMARK OFFICE General Provisions General Information § 11.3 Suspension of rules. (a) In an extraordinary situation, when justice requires...

Role of the Liquids From Coal process in the world energy picture

Energy Technology Data Exchange (ETDEWEB)

Frederick, J.P.; Knottnerus, B.A. [ENCOAL Corp., Gillette, WY (United States)

1997-12-31

ENCOAL Corporation, a wholly owned indirect subsidiary of Zeigler Coal Holding Company, has essentially completed the demonstration phase of a 1,000 Tons per day (TPD) Liquids From Coal (LFC{trademark}) plant near Gillette, Wyoming. The plant has been in operation for 4{1/2} years and has delivered 15 unit trains of Process Derived Fuel (PDF{trademark}), the low-sulfur, high-Btu solid product to five major utilities. Recent test burns have indicated the PDF{trademark} can offer the following benefits to utility customers: lower sulfur emissions, lower NO{sub x} emissions, lower utilized fuel costs to power plants, and long term stable fuel supply. More than three million gallons of Coal Derived Liquid (CDL{trademark}) have also been delivered to seven industrial fuel users and one steel mill blast furnace. Additionally, laboratory characteristics of CDL{trademark} and process development efforts have indicated that CDL{trademark} can be readily upgraded into higher value chemical feedstocks and transportation fuels. Commercialization of the LFC{trademark} is also progressing. Permit work for a large scale commercial ENCOAL{reg_sign} plant in Wyoming is now underway and domestic and international commercialization activity is in progress by TEK-KOL, a general partnership between SGI International and a Zeigler subsidiary. This paper covers the historical background of the project, describes the LFC{trademark} process and describes the worldwide outlook for commercialization.

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.

37 CFR 1.251 - Unlocatable file.

Science.gov (United States)

2010-07-01

..., patent, or other patent-related proceeding after a reasonable search, the Office will notify the... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Unlocatable file. 1.251 Section 1.251 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF...

37 CFR 11.10 - Restrictions on practice in patent matters.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Restrictions on practice in patent matters. 11.10 Section 11.10 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT AND...

37 CFR 1.17 - Patent application and reexamination processing fees.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent application and reexamination processing fees. 1.17 Section 1.17 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES General Provisions Fees...

A big picture prospective for wet waste processing management

International Nuclear Information System (INIS)

Gibson, J.D.

1996-01-01

This paper provides an overview of general observations made relative to the technical and economical considerations being evaluated by many commercial nuclear power plants involving their decision making process for implementation of several new wet waste management technologies. The waste management processes reviewed include the use of, Reverse Osmosis, Non-Precoat Filters, Resin Stripping ampersand Recycling, Evaporation ampersand Calcination (RVR trademark, ROVER trademark ampersand Thermax trademark), Compression Dewatering (PressPak trademark), Incineration (Resin Express trademark), Survey ampersand Free Release (Green Is Clean) and Quantum Catalytic Extraction Processing (QCEP trademark). These waste management processes are reviewed relative to their general advantages and disadvantages associated with the processing of various wet waste streams including: reactor make-up water, floor drain sludges and other liquid waste streams such as boric acid concentrates and steam generator cleaning solutions. A summary of the conclusions generally being derived by most utilities associated with the use of these waste management processes is also provided

77 FR 49425 - Request for Comments Regarding Amending the First Filing Deadline for Affidavits or Declarations...

Science.gov (United States)

2012-08-16

... submitted by mail to Commissioner for Trademarks, P.O. Box 1451, Alexandria, VA 22313-1451, attention Cynthia C. Lynch; by hand delivery to the Trademark Assistance Center, Concourse Level, James Madison... at the time it became incontestable, and to correspond to English law. See Trade-Marks: Hearings on H...

76 FR 40839 - Changes in Requirements for Specimens and for Affidavits or Declarations of Continued Use or...

Science.gov (United States)

2011-07-12

... to a registered mark, or an affidavit or declaration of continued use in trademark cases. The... trademark application, an allegation of use, an amendment to a registered mark, or an affidavit or... entity that has a registered trademark could potentially be impacted by the proposed rules. The USPTO...

37 CFR 1.41 - Applicant for patent.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Applicant for patent. 1.41 Section 1.41 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Who May Apply for A...

37 CFR 1.705 - Patent term adjustment determination.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent term adjustment determination. 1.705 Section 1.705 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Adjustment and Extension of Patent Term...

37 CFR 1.314 - Issuance of patent.

Science.gov (United States)

2010-07-01

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2010-07-01

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2010-07-01

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2010-07-01

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An Evaluation of the NIDS (registered trademark) ACE (trademark) Test

Science.gov (United States)

2014-06-30

of 1) Yes, 52 mg/L Yes 25 mg/L (3 of 3) Cyanide (sodium) 14 Yes (1 of 3) ND Yes, 3.5 mg/L ND Ethylene glycol 3157 ND ND ND --- h Fenamiphos 0.56...wells (upper test well and lower control well). The green color indicates a hydrolysis of the NMI substrate by either enzyme (negative) and the...NMI oxidation (Y. Vallejo, ANP Technologies, personal communication). Table 8. Estimated and Actual Shelf Life Determinations of Enzyme Reagents

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

37 CFR 2.192 - Business to be conducted with decorum and courtesy.

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2010-07-01

... Correspondence in Trademark Cases § 2.192 Business to be conducted with decorum and courtesy. Trademark... attorneys or agents are required to conduct their business with decorum and courtesy. Documents presented in... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Business to be conducted with...

37 CFR 2.99 - Application to register as concurrent user.

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2010-07-01

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Convolutional Neural Network on Embedded Linux System-on-Chip: A Methodology and Performance Benchmark

Science.gov (United States)

2016-05-01

Linux® is a registered trademark of Linus Torvalds. NVIDIA ® is a registered trademark of NVIDIA Corporation. Oracle® is a registered trademark of...two NVIDIA ® GTX580 GPUs [3]. Therefore, for this initial work, we decided to concentrate on small networks and small datasets until the methods are

Study of dosimetric properties of acetylsalicylic acid in pharmaceutical preparations by EPR spectroscopy

International Nuclear Information System (INIS)

Juarez Calderon, J.M.; Negron Mendoza, A.; Ramos Bernal, S.; Gomez Vidales, V.

2008-01-01

Electron paramagnetic resonance (EPR) was used to investigate the dosimetric properties of two pharmaceutical preparations containing acetylsalicylic acid, Aspirin (trademark) and Cafiaspirin (trademark). The EPR spectra of the irradiated samples were found to have an asymmetric absorption characterized by a major resonance at g = 2.0033. Dose response was investigated between dose ranges of 2 to 40 kGy for 60 Co-gamma rays. Fading characteristics and dependence on temperature irradiation were also studied. We suggest that commercial Aspirin (trademark) and Cafiaspirin (trademark) tablets can be used as dosimeters for industrial processes. (author)

BIOTIGER, A NATURAL MICROBIAL PRODUCT FOR ENHANCED HYDROCARBON RECOVERY FROM OIL SANDS.

Energy Technology Data Exchange (ETDEWEB)

Brigmon, R; Topher Berry, T; Whitney Jones, W; Charles Milliken, C

2008-05-27

BioTiger{trademark} is a unique microbial consortia that resulted from over 8 years of extensive microbiology screening and characterization of samples collected from a century-old Polish waste lagoon. BioTiger{trademark} shows rapid and complete degradation of aliphatic and aromatic hydrocarbons, produces novel surfactants, is tolerant of both chemical and metal toxicity and shows good activity at temperature and pH extremes. Although originally developed and used by the U.S. Department of Energy for bioremediation of oil-contaminated soils, recent efforts have proven that BioTiger{trademark} can also be used to increase hydrocarbon recovery from oil sands. This enhanced ex situ oil recovery process utilizes BioTiger{trademark} to optimize bitumen separation. A floatation test protocol with oil sands from Ft. McMurray, Canada was used for the BioTiger{trademark} evaluation. A comparison of hot water extraction/floatation test of the oil sands performed with BioTiger{trademark} demonstrated a 50% improvement in separation as measured by gravimetric analysis in 4 h and a five-fold increase at 25 hr. Since BioTiger{trademark} performs well at high temperatures and process engineering can enhance and sustain metabolic activity, it can be applied to enhance recovery of hydrocarbons from oil sands or other complex recalcitrant matrices.

Xyce Parallel Electronic Simulator Reference Guide Version 6.7.

Energy Technology Data Exchange (ETDEWEB)

Keiter, Eric R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Aadithya, Karthik Venkatraman [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mei, Ting [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Russo, Thomas V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Schiek, Richard [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sholander, Peter E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Thornquist, Heidi K. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Verley, Jason [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-05-01

This document is a reference guide to the Xyce Parallel Electronic Simulator, and is a companion document to the Xyce Users' Guide [1] . The focus of this document is (to the extent possible) exhaustively list device parameters, solver options, parser options, and other usage details of Xyce . This document is not intended to be a tutorial. Users who are new to circuit simulation are better served by the Xyce Users' Guide [1] . The information herein is subject to change without notice. Copyright c 2002-2017 Sandia Corporation. All rights reserved. Trademarks Xyce TM Electronic Simulator and Xyce TM are trademarks of Sandia Corporation. Orcad, Orcad Capture, PSpice and Probe are registered trademarks of Cadence Design Systems, Inc. Microsoft, Windows and Windows 7 are registered trademarks of Microsoft Corporation. Medici, DaVinci and Taurus are registered trademarks of Synopsys Corporation. Amtec and TecPlot are trademarks of Amtec Engineering, Inc. All other trademarks are property of their respective owners. Contacts World Wide Web http://xyce.sandia.gov https://info.sandia.gov/xyce (Sandia only) Email xyce@sandia.gov (outside Sandia) xyce-sandia@sandia.gov (Sandia only) Bug Reports (Sandia only) http://joseki-vm.sandia.gov/bugzilla http://morannon.sandia.gov/bugzilla

The social cure: identity, health and well-being

National Research Council Canada - National Science Library

Jetten, Jolanda; Haslam, Catherine; Haslam, S. Alexander

2012-01-01

... known or hereafter invented, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers. Trademark notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identi®cation and explanation without intent to infringe. British Library Cata...

Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System

Energy Technology Data Exchange (ETDEWEB)

Wang, Wenjie [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China); Luo, Judong [Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou (China); Sheng, Wenjiong; Xue, Jiao; Li, Ming [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Ji, Jiang [Department of Dermatology, the Second Affiliated Hospital of Soochow University, Suzhou (China); Liu, Pengfei [Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin (China); Zhang, Xueguang [Institute of Medical Biotechnology and Jiangsu Stem Cell Key Laboratory, Medical College of Soochow University, Suzhou (China); Cao, Jianping [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China)

2016-06-01

Purpose: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. Methods and Materials: Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence. The efficacy of bortezomib in wound healing of rat skin was assessed by the skin injury scale. Results: We found that irradiation induced epidermal and dermal hyperplasia in rat and human skin. One hundred ninety-six preferentially expressed and 80 unique proteins in the irradiated fibrotic skin were identified. Through bioinformatic analysis, the ubiquitin-proteasome pathway showed a significant fold change and was investigated in greater detail. In vitro experiments demonstrated that irradiation resulted in a decline in the activity of the proteasome in human skin cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-β downstream signaling but not TGF-β secretion stimulated by irradiation in HaCaT and WS-1 cells. Moreover, bortezomib ameliorated radiation-induced skin injury and attenuated epidermal hyperplasia. Conclusion: Our findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.

Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

Directory of Open Access Journals (Sweden)

Catriona Elizabeth Mactier

2012-10-01

Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

Treatment of the femoropopliteal arteries with a novel rotational atherectomy system: early single-center experience with the Pathway PV trademark Atherectomy System

International Nuclear Information System (INIS)

Wissgott, C.; Kamusella, P.; Richter, A.; Steinkamp, H.J.; Schink, T.; Klein-Weigel, P.

2008-01-01

Purpose: The main problem when treating the superficial femoral and popliteal artery with PTA or stent implantation is the relatively high restenosis rate. Several ablative systems are available as an alternative. The purpose of this prospective study was to evaluate the safety and performance of a novel rotational and aspirating atherectomy system. Materials and Methods: From June to December 2006, we treated 23 patients, median age 70.3 years (58 - 91), with the rotational atherectomy system. All patients had de-novo lesions of the SFA or PA with a minimum stenosis of 70%. According to the Rutherford classification, 39% of the patients were in category 2 and 61% in category 3. The median lesion length was 26.3 mm (5 - 100 mm). 26% of the patients had occlusions. Results: The technical success rate was 100%. In 14 cases (61%) additional balloon dilatation was applied, in two cases stent implantation were performed. The median treatment duration with the device was 187.7 ± 106.1 s (59 - 391 s). The aspirated volume was 116.5 ± 72.0 ml. The ankle brachial index improved from preinterventional 0.60 ± 0.16 to postinterventional 0.85 ± 0.13 and after 6 month 0.80 ± 0.13. During follow-up, two (8%) restenosis occurred. There were two complications, one dissection and one distal embolization. Follow-up could not be performed for two patients (8%). Conclusion: Atherectomy of femoropopliteal lesions with the Pathway PV trademark Atherectomy System is very safe and effective. The low restenosis rate of 8% is promising, but there is still a lack of long-term results

15 CFR 9.2 - Definitions.

Science.gov (United States)

2010-01-01

... means the Secretary of Commerce. (b) The term manufacturer means any person engaged in the manufacturing... products for sale or resale, or any person whose brand or trademark appears on such products who owns such brand or trademark and has authorized its use on such products, if the brand or trademark of the person...

37 CFR 7.26 - Filing date of extension of protection for purposes of examination in the Office.

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2010-07-01

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2010-07-01

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37 CFR 41.153 - Records of the Office.

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2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Records of the Office. 41.153 Section 41.153 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE PRACTICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES Contested Cases § 41.153 Records of the Office. Certification is not...

16 CFR 1211.22 - Definitions.

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2010-01-01

... definitions shall apply to this subpart: (a) Private labeler means an owner of a brand or trademark which is used on an operator subject to the standard and which is not the brand or trademark of the manufacturer of the operator, provided the owner of the brand or trademark caused or authorized the operator to be...

Overall survival patterns in patients with multiple myeloma in the era of novel agents and the role of initial clinical presentation and comorbidities: A population-based study

NARCIS (Netherlands)

Oortgiesen, Berdien; Van Roon, Eric N.; Joosten, Peter; Kibbelaar, Robby; Storm, Huib; Hovenga, Sjoerd; Van Rees, Bas P.; Woolthuis, Gerhard; Veeger, Nic J. G. M.; Hoogendoorn, Mels

2014-01-01

Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting

Assessing Security Cooperation as a Preventive Tool

Science.gov (United States)

2014-01-01

Reports & Bookstore Make a charitable contribution Limited Electronic Distribution Rights This document and trademark(s) contained herein are protected by...deductible charitable contribution at www.rand.org/giving/contribute.html R® is a registered trademark © Copyright 2014 RAND Corporation This document...OECD—See Organisation for Economic Co-Operation and Development. Organisation for Economic Co-Operation and Development, Development Assistance

Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece

Directory of Open Access Journals (Sweden)

Fragoulakis V

2013-04-01

Full Text Available V Fragoulakis,1 E Kastritis,2 T Psaltopoulou,3 N Maniadakis1 1National School of Public Health, Athens, Greece; 2Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM, the aim of this study was to assess the cost-effectiveness of the combination of lenalidomide–dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX. Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs was 3.01 (95% UI 2.81–3.20 and 2.22 (95% UI 2.02–2.41 for lenalidomide–dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49–1.06 QALYs in favor of lenalidomide–dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509�

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

Investigation of the potential of silica-bonded macrocyclic ligands for separation of metal ions from nuclear waste

International Nuclear Information System (INIS)

Camaioni, D.M.; Colton, N.G.; Bruening, R.L.

1992-01-01

This report describes the testing of some novel separations materials known as SuperLig trademark materials for their ability to separate efficiently and selectively certain metal ions from a synthetic, nonradioactive nuclear waste solution. The materials, developed and patented by IBC Advanced Technologies, are highly selective macrocyclic ligands that have been covalently bonded to silica gel. The SuperLig trademark materials that were tested are: (1) SuperLig trademark 601 for barium (Ba 2+ ) and strontium (Sr 2+ ) separation, (2) SuperLig trademark 602 for cesium (Cs + ) and rubidium (Rb + ) separation, (3) SuperLig trademark 27 for palladium (Pd 2+ ) separation, and (4) SuperLig trademark II for silver (Ag + ) and ruthenium (Ru 3+ ) separation. Our observations show that the technology for separating metal ions using silica-bonded macrocycles is essentially sound and workable to varying degrees of success that mainly depend on the affinity of the macrocycle for the metal ion of interest. It is expected that ligands will be discovered or synthesized that are amenable to separating metal ions of interest using this technology. Certainly more development, testing, and evaluation is warranted. 3 figs., 11 tabs

Field application of the Numobag as a portable disposable isolation unit and for treating chemical, radiological or biologically induced wounds.

Energy Technology Data Exchange (ETDEWEB)

Miller, Keith A.; Felton, Robert; Vaughan, Courtenay Thomas

2005-04-01

Numotech Inc. has developed the Numobag{trademark}, a disposable, lightweight, wound healing device which produces Topical Hyperbaric Oxygen Therapy (THOT). The Numobag{trademark} is cost effective and has been clinically validated to heal large skin lesions rapidly and has proven to arrest wound advancement from several insidious forms of biological attack including dermal anthrax, small pox, necrotizing fasciitis etc. The Numobag{trademark} can treat mass casualties wounded by chemical/radiological burns or damaging biological exposures. The Numobag{trademark} can be a frontline tool as an isolation unit, reducing cross-contamination and infection of medical personnel. The heightened oxygen content kills organisms on the skin and in the wound, avoids expensive hospital trash disposal procedures, and helps the flesh heal. The Numobag{trademark} requires high purity oxygen. Numotech Inc. is teaming with Sandia National Laboratories and Spektr Conversion in Russia to develop a cost effective, portable, low power oxygen generator.

Late diagnosis of multiple myeloma: a case report

Science.gov (United States)

Syahreza, A.; Gatot, D.; Mardia, A. I.

2018-03-01

Multiple myeloma is a challenging hematologic case to handle. Sometimes the disease is diagnosed too late for the patient and doctor. Therefore, careful approaches are needed to manage the patient. A 66-year-old mansuffersfrom low back pain since one year before he came to the hospital. He was diagnosed multiple compression fractures by orthopedic and had undergone two surgeries in one year. Punched out lesions werein skull radiology and lumbar compression in lumbar MRI. After further investigation, plasmacytoma and M protein in urine electrophoresis were founded. Significant improvement found after bortezomib and dexamethasone were given.Diagnosis and management of multiple myeloma is a challenge for a doctor. Systematically approach is needed for a patient with a recurrent fracture. Even a novel therapies are not widely available in our country.We reported a late diagnosis of multiple myeloma and had a significant improvement after bortezomib and dexamethasone therapy.

Management of cutaneous T cell lymphoma: new and emerging targets and treatment options

Directory of Open Access Journals (Sweden)

Li JY

2012-03-01

Full Text Available Janet Y Li1, Steven Horwitz2, Alison Moskowitz2, Patricia L Myskowski3, Melissa Pulitzer4, Christiane Querfeld31College of Physicians and Surgeons, Columbia University, 2Department of Medicine, Lymphoma Service, 3Department of Medicine, Dermatology Service, 4Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USAAbstract: Cutaneous T cell lymphomas (CTCL clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin, and pralatrexate in CTCL.Keywords: novel targets, histone deacetylase inhibitors, pralatrexate, bortezomib, cutaneous T cell lymphoma

Prolonged early G1 arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle–coupled loss of IRF4

Science.gov (United States)

Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L.; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C.; Staudt, Louis M.; Niesvizky, Ruben; Moore, Malcolm A. S.

2012-01-01

Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G1 block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy. PMID:22718837

Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4.

Science.gov (United States)

Huang, Xiangao; Di Liberto, Maurizio; Jayabalan, David; Liang, Jun; Ely, Scott; Bretz, Jamieson; Shaffer, Arthur L; Louie, Tracey; Chen, Isan; Randolph, Sophia; Hahn, William C; Staudt, Louis M; Niesvizky, Ruben; Moore, Malcolm A S; Chen-Kiang, Selina

2012-08-02

Dysregulation of cyclin-dependent kinase 4 (CDK4) and CDK6 by gain of function or loss of inhibition is common in human cancer, including multiple myeloma, but success in targeting CDK with broad-spectrum inhibitors has been modest. By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. We show that induction of prolonged early-G(1) arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G(1) and prevents expression of genes programmed for other cell-cycle phases. Removal of the early-G(1) block leads to S-phase synchronization (pG1-S) but fails to completely restore scheduled gene expression. Consequently, the IRF4 protein required to protect myeloma cells from apoptosis is markedly reduced in pG1 and further in pG1-S in response to cytotoxic agents, such as the proteasome inhibitor bortezomib. The coordinated loss of IRF4 and gain of Bim sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 in the absence of Noxa and more profoundly in pG1-S in cooperation with Noxa in vitro. Induction of pG1 and pG1-S by reversible CDK4/CDK6 inhibition further augments tumor-specific bortezomib killing in myeloma xenografts. Reversible inhibition of CDK4/CDK6 in sequential combination therapy thus represents a novel mechanism-based cancer therapy.

Treatment of Antibody-Mediated Renal Allograft Rejection: Improving Step by Step

Directory of Open Access Journals (Sweden)

Nils Lachmann

2017-01-01

Full Text Available Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR. Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg, low-dose (30 g intravenous immunoglobulins (IVIG, and plasmapheresis (PPH, 6x (group RLP, n=12. Between 2009 and June 2010, patients received bortezomib (1.3 mg/m2, 4x together with low-dose IVIG and PPH (group BLP, n=11. In July 2010, we increased the IVIG dose and treated all subsequent patients with bortezomib, high-dose IVIG (1.5 g/kg, and PPH (group BHP, n=11. Graft survival at three years after treatment was 73% in group BHP as compared to 45% in group BLP and 25% in group RLP. At six months after treatment median serum creatinine was 2.1 mg/dL, 2.9 mg/dL, and 4.2 mg/dL in groups BHP, BLP, and RLP, respectively (p=0.02. Following treatment, a significant decrease of donor-specific HLA antibody (DSA mean fluorescence intensity from 8467±6876 to 5221±4711 (p=0.01 was observed in group BHP, but not in the other groups. Our results indicate that graft survival, graft function, and DSA levels could be improved along with stepwise modifications to our treatment regimen, that is, the introduction of bortezomib and high-dose IVIG treatment.

Prekių ženklo licencinės sutarties ir franšizės sutarties santykis

OpenAIRE

Želvys, Arūnas

2009-01-01

The article investigates the correlation between franchise agreement and trademark license under the provisions of Lithuanian Civil Code and Trademark Law. The analysis shows that both contracts are autonomous and trademark license is usually the "core" inside of a franchise agreement. Franchise agreement is qualified mainly on the analysis of rights and obligations of the parties, the most important of which is quality control provision. Despite the fact that franchise agreement regulations ...

76 FR 55841 - Extension of Comment Period for Notice of Proposed Rulemaking on Changes in Requirements for...

Science.gov (United States)

2011-09-09

...-delivery to the Trademark Assistance Center, Concourse Level, James Madison Building-East Wing, 600 Dulany... Office of the Commissioner for Trademarks, Madison East, Tenth Floor, 600 Dulany Street, Alexandria...

Novel agents in CNS myeloma treatment.

Science.gov (United States)

Gozzetti, Alessandro; Cerase, Alfonso

2014-01-01

Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo.

Science.gov (United States)

Schnerch, Dominik; Schüler, Julia; Follo, Marie; Felthaus, Julia; Wider, Dagmar; Klingner, Kathrin; Greil, Christine; Duyster, Justus; Engelhardt, Monika; Wäsch, Ralph

2017-03-28

Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

Directory of Open Access Journals (Sweden)

Annalisa Canta

2015-06-01

Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Science.gov (United States)

Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

2015-01-01

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

37 CFR 10.38 - Agreements restricting the practice of a practitioner.

Science.gov (United States)

2010-07-01

... AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE PATENT AND TRADEMARK... payment of retirement benefits. (b) In connection with the settlement of a controversy or suit, a...

77 FR 58097 - Extension of Comment Period for Request for Comments Regarding Amending the First Filing Deadline...

Science.gov (United States)

2012-09-19

... Trademark Assistance Center, Concourse Level, James Madison Building-- East Wing, 600 Dulany Street... , and will also be available at the Office of the Commissioner for Trademarks, Madison East, Tenth Floor...

The Private Legal Governance of Domain Names

DEFF Research Database (Denmark)

Schovsbo, Jens Hemmingsen

2016-01-01

This chapter evaluates the performance of the special private tribunals or panels such as the UDRP which have been developed within complicated systems of self- and co-regulation such as ICANN to decide disputes over domain names. It uses two different dispute resolution models viz. the UDRP (WIP...... trademarks are used as (parts of) domain names to express criticism of the trademark holder or the trademark itself (e.g. “TMsucks.com” / “lorteTM.dk”)....