WorldWideScience

Sample records for chemopreventive agent repository

  1. Polyphenols as cancer chemopreventive agents.

    Science.gov (United States)

    Stoner, G D; Mukhtar, H

    1995-01-01

    This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems. Emphasis is placed upon the anticarcinogenic activity of these polyphenols and their proposed mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Tea is manufactured as either green, black, or oolong; black tea represents approximately 80% of tea products. Epidemiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimutagenic and anticarcinogenic effects of tea have been conducted principally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although several GTPs possess anticarcinogenic activity, the most active is (-)-epigallocatechin-3-gallate (EGCG), the major constituent in the GTP fraction. Several mechanisms appear to be responsible for the tumor-inhibitory properties of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of chemically induced lipid peroxidation; inhibition of irradiation- and TPA-induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibition of protein kinase C and cellular proliferation; antiinflammatory activity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice tumeric. It exhibits antimutagenic activity in the Ames Salmonella test and has anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestomach, duodenum and colon of rodents. In addition

  2. Beneficial and adverse effects of chemopreventive agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-03-01

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

  3. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy

    Institute of Scientific and Technical Information of China (English)

    Fazlul H SARKAR; Yi-wei LI

    2007-01-01

    In recent years, growing interest has been focused on the field of cancer prevention.Cancer prevention by chemopreventive agents offers significant promise for re-ducing the incidence and mortality of cancer. Chemopreventive agents may exert their effects either by blocking or metabolizing carcinogens or by inhibiting tumor cell growth. Another important benefit of chemopreventive agents is their non-toxic nature. Therefore, chemopreventive agents have recently been used for cancer treatment in combination with chemotherapeutics or radiotherapy, uncov-ering a novel strategy for cancer therapy. This strategy opens a new avenue fromcancer prevention to cancer treatment. In vitro and in vivo studies have demon-strated that chemopreventive agents could enhance the antitumor activity of chemotherapeutics, improving the treatment outcome. Growing evidence has shown that chemopreventive agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways, including Akt, NF-κB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. However, further in-depth mecha-nistic studies, in vivo animal experiments, and clinical trials are needed to investi-gate the effects of chemopreventive agents in combination treatment of cancer with conventional cancer therapies. More potent natural and synthetic chemo-preventive agents are also needed to improve the efficacy of mechanism-based and targeted therapeutic strategies against cancer, which are likely to make a significant impact on saving lives. Here, we have briefly reviewed the role of chemopreventive agents in cancer prevention, but most importantly, we have reviewed how they could be useful for cancer therapy in combination with con-ventional therapies.

  4. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  5. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Science.gov (United States)

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

  6. Plant Polyphenols as Chemopreventive Agents for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Madumani Amararathna

    2016-08-01

    Full Text Available Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases.

  7. Plant Polyphenols as Chemopreventive Agents for Lung Cancer

    Science.gov (United States)

    Amararathna, Madumani; Johnston, Michael R.; Rupasinghe, H. P. Vasantha

    2016-01-01

    Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

  8. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    Science.gov (United States)

    2005-03-01

    squamous cell or basal cell carcinoma , ing for smoking exposure, non-tumorous lung tissue melanoma); oropharyngeal; hepatocellular carcinoma ; of women...supplementation on cancer incidence in a randomized clinical squamous cell carcinoma of the skin in relation to plasma trial: a summary report of the...invasive carcinoma . In vivo screening of promising chemopreventive agents using the dog model of spontaneous prostate carcinogenesis represents a novel

  9. Expression of Metabolic and Apoptotic Genes During Treatment With Chemopreventive Agents for Breast Cancer

    Science.gov (United States)

    2005-07-01

    Minneapolis, MN. Cancer -preventive properties of the components of cruciferous vegetables including indoles have been studied extensively. 3,3...carbinol (13C) is a product of autolysis from glucobrassicin in cruciferous vegetables . It is condensed to 3,3’-diindolylmethane (DIM) and other products in...AD Award Number: DAMD17-01-1-0332 TITLE: Expression of Metabolic and Apoptotic Genes During Treatment with Chemopreventive Agents for Breast Cancer

  10. Analysis of in vitro chemoprevention of genotoxic damage by phytochemicals, as single agents or as combinations.

    Science.gov (United States)

    Abraham, Suresh K; Eckhardt, Alexander; Oli, Rajaraman G; Stopper, Helga

    2012-05-15

    Cancer chemoprevention with low-dose combinations of bioactive phytochemicals instead of single agents has been suggested to induce less toxicity and improve efficacy. In this study, we selected four plant food-based phytochemicals, viz. chlorogenic acid (CLA), pelargonidin (PEL), resveratrol (RES) and epigallocatechin gallate (EGCG) to evaluate the in vitro chemoprevention of genotoxic damage in HL-60 cells. These agents were tested either individually or as a combination at two concentrations (with a 10-fold difference) against the genotoxins mitomycin C (MMC), diepoxybutane (DEB) and patulin (PAT). Our preliminary ferric reducing antioxidant power (FRAP) assay demonstrated additive effects when PEL, CLA, RES and EGCG were combined. Results of the cytokinesis-block micronucleus test showed significant protection against genotoxic damage induced by PAT, DEB and MMC when CLA, PEL, RES and EGCG were tested individually. This protective effect of the phytochemicals was not concentration-related. Both low- and high-concentration combinations of CLA, PEL, RES and EGCG showed significant reducing effects on the frequencies of micronuclei induced by PAT, DEB and MMC. However, the micronucleus test did not provide indications of additive or synergistic effects with this combination of phytochemicals. In conclusion, the chemo-preventive effects of PEL, CLA, RES and EGCG against genotoxic damage induced by MMC, DEB and PAT are indicative of a 'saturation effect' when higher concentrations and combinations of these phytochemicals are used.

  11. Phase 0 Trials: Expediting the Development of Chemoprevention Agents

    OpenAIRE

    Kummar, Shivaani; Doroshow, James H.

    2011-01-01

    Phase 0 trials are first-in-human clinical trials performed under the Exploratory IND [investigational new drug] Guidance of the US Food and Drug Administration. Unlike traditional phase I trials, these studies have no therapeutic or diagnostic intent but instead aim to provide only pharmacokinetic and/or pharmacodynamic data to inform the next step in developing an agent. We discuss the role that such trials, including one reported by Reid et al. (beginning on page XXX in this issue of the j...

  12. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents.

    Science.gov (United States)

    Meiyanto, Edy; Hermawan, Adam; Anindyajati

    2012-01-01

    Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product

  13. Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention 

    Directory of Open Access Journals (Sweden)

    Łukasz Dobrek

    2012-09-01

    Full Text Available The use of oxazaphosphorines (cyclophosphamide, ifosfamide in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite – acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation.The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned. 

  14. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Pierre Desreumaux

    2005-01-01

    Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer

  15. LEARNING REPOSITORY ADAPTABILITY IN AN AGENT-BASED UNIVERSITY ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Vanco Cabukovski

    2016-06-01

    Full Text Available Automated e-Learning Systems (AeLS are fundamental to contemporary educational concepts worldwide.It has become a standard not only in support to the formal curriculum, but containing social platform capabilities, gamification elements and functionalities fostering communities of experts, also for faster knowledge dissemination. Additionally, AeLSs support internal communications and customizable analytics and methodologies to quickly identify learning performance, which in turn can be used as feedback to implement adaptability in tailoring the content management to meet specific individual needs. The volume of fast growing AeLS content of supplement material and exchanged communication combined with the already huge material archived in the university libraries is enormous and needs sophisticated managing through electronic repositories. Such integration of content management systems (CMS present challenges which can be solved optimally with the use of distributed management implemented through agent-based systems. This paper depicts a successful implementation of an Integrated Intelligent Agent Based UniversityInformation System (IABUIS.

  16. Tea: age-old beverage as an effective cancer chemopreventive agent

    Directory of Open Access Journals (Sweden)

    Jasmine George

    2011-12-01

    Full Text Available Cancer is the major public health problem, causing approximately 7 million deaths every year worldwide. The existing treatment approaches and surgical techniques have not been able to cope effectively with this dreaded disease. Because of this, the concept of chemoprevention is now considered a valid approach to reduce the incidence of cancer. There is convincing epidemiological and experimental evidence to show that dietary polyphenolic plant-derived compounds have cancer preventive properties. Based on evidence from in vitro, in vivo data and epidemiological studies, tea has received considerable attention over recent years for reducing the risk of several cancers. Much of the cancer preventive effects of tea, and in particular green tea, appear to be mediated by the polyphenols they contain. In addition to inhibiting mutagenesis and proliferation, tea is relatively non-toxic, is low cost, and can be taken orally or as a part of the daily diet. Therefore it is logical that future clinical studies should focus on examining the efficacy of tea and its active constituents, such as epigallocatechin- 3-gallate (EGCG and theaflavins (TFs, in chemoprevention as an alternative to pharmacological agents. In this review, we address the use of tea and its constituents for the prevention and treatment of cancer. Further mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

  17. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2011-01-01

    Full Text Available Head and neck squamous cell cancer (HNSCC is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms.

  18. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Zhao, Yuan; Guo, Yinhan; Gu, Xinbin

    2011-01-01

    Head and neck squamous cell cancer (HNSCC) is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B) isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms. PMID:21209716

  19. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    Science.gov (United States)

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes.

  20. Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response.

    Directory of Open Access Journals (Sweden)

    Ramesh K Wali

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21(cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis.

  1. Dietary Pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    Science.gov (United States)

    Dietary nutrients with ability to reverse adverse epigenetic events have great potential for cancer chemoprevention. Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1-d...

  2. Sugar-borate esters--potential chemical agents in prostate cancer chemoprevention.

    Science.gov (United States)

    Scorei, Romulus Ion; Popa, Radu

    2013-07-01

    The potential value of sugar-borate esters (SBEs) in the chemo-preventive therapy of prostate cancer has been reviewed. We propose that SBEs act as boron (B) vehicles, increasing the concentration of borate inside cancer cells relative to normal cells. Increased intracellular concentration of borate activates borate transporters, but also leads to growth inhibition and apoptosis. The effects of SBEs on normal cells are less dramatic because SBEs are naturally-occurring biochemicals, common and abundant in some fruits and vegetables, and also because borate dissociated from SBEs in natural diet doses is easily exported from normal cells. Cancer cell lines that over-express sugar transporters or under-express borate export are potential targets for SBE-based therapy. With regard to efficiency against cancer cells and drug preparation requirements, trigonal cis-diol boric monoesters will be one of the most effective class of SBEs. Because negative correlation exists between borate intake and the incidence of prostate cancer, and because most cancer cells overexpress sugar transporters, SBEs are proposed as a potential chemopreventive avenue in the fight against primary and recurrent prostate cancer.

  3. Kaiware Daikon (Raphanus sativus L.) extract: a naturally multipotent chemopreventive agent.

    Science.gov (United States)

    Barillari, Jessica; Iori, Renato; Papi, Alessio; Orlandi, Marina; Bartolini, Giovanna; Gabbanini, Simone; Pedulli, Gian Franco; Valgimigli, Luca

    2008-09-10

    Brassica vegetables are attracting major attention as healthy foods because of their content of glucosinolates (GLs) that release the corresponding isothiocyanates (ITCs) upon myrosinase hydrolysis. A number of studies have so far documented the chemopreventive properties of some ITCs. On the other hand, single nutrients detached from the food itself risk being somewhat "reductive", since plants contain several classes of compounds endowed with a polyhedral mechanism of action. Our recent finding that 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) and 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC), released by the GLs purified from Japanese (Kaiware) Daikon (Raphanus sativus L.) seeds and sprouts, had selective cytotoxic/apoptotic activity on three human colon carcinoma cell lines prompted further research on the potential chemopreventive role of a standardized Kaiware Daikon extract (KDE), containing 10.5% w/w GRH and 3.8% w/w GRE, compared to its isolated components. KDE administered in combination with myrosinase at doses corresponding to 50 microM GRH-ITC plus 15 microM GRE-ITC (50 microM KDE-ITC) to three human cancer cell lines (LoVo, HCT-116 and HT-29) significantly reduced cell growth by 94-96% of control in six days (p GRH-ITC or GRE-ITC at the same dose. On the other hand, the same treatment had no significant toxicity on normal human T-lymphocytes. A 50 microM concentration of KDE-ITC had relevant apoptosis induction in all tested cancer cell lines, as confirmed by annexin V assay (e.g., 33% induction in LoVo compared to control, p GRH or GRH-ITC, KDE also had significant chain-breaking antioxidant activity, retarding the AAPH-initiated autoxidation of methyl linoleate in SDS micelles at concentrations as low as 4.4 ppm (-50% in oxygen consumption rate), as monitored by Clark-type microelectrode oxygen-uptake kinetics, and induced very fast quenching of DPPH. radical in methanol with t(1/2) (s) = (1.47 +/- 0.25) x 10(-2)/[KDE; (g/L)], measured by

  4. Current status of oral cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Moni Abraham Kuriakose

    2008-01-01

    @@ Chemoprevention is the administration of agents to block or reverse carcinogenesis. Chemoprevention in oral cancer has been directed towards reversal of premalignant lesion and prevention of second primary tumor.

  5. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    Science.gov (United States)

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

  6. Endoscopic spectral domain optical coherence tomography of murine colonic morphology to determine effectiveness of chemopreventive and chemotherapeutic agents in colorectal cancer

    Science.gov (United States)

    LeGendre-McGhee, Susan; Rice, Photini F. S.; Wall, R. Andrew; Klein, Justin; Luttman, Amber; Sprute, Kyle; Gerner, Eugene; Barton, Jennifer K.

    2012-02-01

    Optical coherence tomography (OCT) is a minimally-invasive imaging modality capable of tracking the development of individual colonic adenomas. As such, OCT can be used to evaluate the mechanisms and effectiveness of chemopreventive and chemotherapeutic agents in colorectal cancer models. The data presented here represent part of a larger study evaluating α-difluoromethylornithine (DFMO) and Sulindac as chemopreventive and chemotherapeutic agents using mice treated with the carcinogen azoxymethane (AOM). 27 A/J mice were included in the chemoprevention study, subdivided into four treatment groups (No Drug, DFMO, Sulindac, DFMO/Sulindac). 30 mm lateral images of each colon at eight different rotations were obtained at five different time points using a 2 mm diameter spectral domain OCT endoscopy system centered at 890 nm with 3.5 μm axial resolution in air and 5 μm lateral resolution. Images were visually analyzed to determine number and size of adenomas. Gross photos of the excised colons and histology provided gold standard confirmation of the final imaging time point. Preliminary results show that 100% of mice in the No Drug group developed adenomas over the course of the chemoprevention study. Incidence was reduced to 71.43% in mice given DFMO, 85.71% for Sulindac and 0% for DFMO/Sulindac. Discrete adenoma size did not vary significantly between experimental groups. Additional experiments are currently under way to verify these results and evaluate DFMO and Sulindac for chemotherapeutic applications.

  7. Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    Full Text Available Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO, the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice.In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4, product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.

  8. Relationships between pulmonary micro-RNA and proteome profiles, systemic cytogenetic damage and lung tumors in cigarette smoke-exposed mice treated with chemopreventive agents.

    Science.gov (United States)

    Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; La Maestra, Sebastiano; Micale, Rosanna T; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

    2013-10-01

    Assessing the correlation between molecular endpoints and cancer induction or prevention aims at validating the use of intermediate biomarkers. We previously developed murine models that are suitable to detect both the carcinogenicity of mainstream cigarette smoke (MCS) and the induction of molecular alterations. In this study, we used 931 Swiss mice in two parallel experiments and in a preliminary toxicity study. The chemopreventive agents included vorinostat, myo-inositol, bexarotene, pioglitazone and a combination of bexarotene and pioglitazone. Pulmonary micro-RNAs and proteins were evaluated by microarray analyses at 10 weeks of age in male and female mice, either unexposed or exposed to MCS since birth, and either untreated or receiving each one of the five chemopreventive regimens with the diet after weaning. At 4 months of age, the frequency of micronucleated normochromatic erythrocytes was evaluated. At 7 months, the lungs were subjected to standard histopathological analysis. The results showed that exposure to MCS significantly downregulated the expression of 79 of 694 lung micro-RNAs (11.4%) and upregulated 66 of 1164 proteins (5.7%). Administration of chemopreventive agents modulated the baseline micro-RNA and proteome profiles and reversed several MCS-induced alterations, with some intergender differences. The stronger protective effects were produced by the combination of bexarotene and pioglitazone, which also inhibited the MCS-induced clastogenic damage and the yield of malignant tumors. Pioglitazone alone increased the yield of lung adenomas. Thus, micro-RNAs, proteins, cytogenetic damage and lung tumors were closely related. The molecular biomarkers contributed to evaluate both protective and adverse effects of chemopreventive agents and highlighted the mechanisms involved.

  9. The model repository of the models of infectious disease agent study.

    Science.gov (United States)

    Cooley, Phillip C; Roberts, D; Bakalov, V D; Bikmal, S; Cantor, S; Costandine, T; Ganapathi, L; Golla, B J; Grubbs, G; Hollingsworth, C; Li, S; Qin, Y; Savage, William; Simoni, D; Solano, E; Wagener, D

    2008-07-01

    The model repository (MREP) is a relational database management system (RDBMS) developed under the auspices of models of infectious disease agent study (MIDAS). The purpose of the MREP is to organize and catalog the models, results, and suggestions for using the MIDAS and to store them in a way to allow users to run models from an access-controlled disease MREP. The MREP contains source and object code of disease models developed by infectious disease modelers and tested in a production environment. Different versions of models used to describe various aspects of the same disease are housed in the repository. Models are linked to their developers and different versions of the codes are tied to Subversion, a version control tool. An additional element of the MREP will be to house, manage, and control access to a disease model results warehouse, which consists of output generated by the models contained in the MREP. The result tables and files are linked to the version of the model and the input parameters that collectively generated the results. The result tables are warehoused in a relational database that permits them to be easily identified, categorized, and downloaded.

  10. Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Hansen, Marianne; Paulin, H.

    2004-01-01

    This study investigated the speciation and bioavailability of selenium in yeast-based intervention agents from multiple manufacturers from several time points. Sources of selenized yeast included Nutrition 21 (San Diego, CA), which supplied the Nutritional Prevention of Cancer (NPC) Trial from 1981......-1996; Cypress Systems (Fresno, CA; 1997-1999); and Pharma Nord (Vejle, Denmark; 1999-2000), which supplied the Prevention of Cancer by Intervention by Selenium (PRECISE) Trial pilot studies. The low-molecular-selenium species were liberated from the samples by proteolytic hydrolysis followed by separation...

  11. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

    2013-05-01

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

  12. Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2013-09-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group or 34 weeks (15 mice/group to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001 lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001 lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.

  13. BROA: An agent-based model to recommend relevant Learning Objects from Repository Federations adapted to learner profile

    Directory of Open Access Journals (Sweden)

    Paula A. Rodríguez

    2013-03-01

    Full Text Available Learning Objects (LOs are distinguished from traditional educational resources for their easy and quickly availability through Web-based repositories, from which they are accessed through their metadata. In addition, having a user profile allows an educational recommender system to help the learner to find the most relevant LOs based on their needs and preferences. The aim of this paper is to propose an agent-based model so-called BROA to recommend relevant LOs recovered from Repository Federations as well as LOs adapted to learner profile. The model proposed uses both role and service models of GAIA methodology, and the analysis models of the MAS-CommonKADS methodology. A prototype was built based on this model and validated to obtain some assessing results that are finally presented.

  14. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  15. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. [Argonne National Lab., IL (United States)]|[Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Carnes, B.A. [Argonne National Lab., IL (United States)

    1993-05-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL {times} BALB/c F{sub 1} female mice, were exposed to a single whole-body dose of 206 cGy from a {sup 60}Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival.

  16. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. (Argonne National Lab., IL (United States) Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology); Carnes, B.A. (Argonne National Lab., IL (United States))

    1993-01-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL [times] BALB/c F[sub 1] female mice, were exposed to a single whole-body dose of 206 cGy from a [sup 60]Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival.

  17. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Perocco, Paolo [Department of Experimental Pathology, Cancerology Section, viale Filopanti 22, I-40126, University of Bologna, Bologna (Italy); Bronzetti, Giorgio [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy); Canistro, Donatella; Sapone, Andrea; Affatato, Alessandra; Pozzetti, Laura; Broccoli, Massimiliano [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Valgimigli, Luca [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Pedulli, Gian Franco [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Iori, Renato [C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Barillari, Jessica [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy)]|[C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Sblendorio, Valeriana [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Legator, Marvin S. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States); Paolini, Moreno [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Abdel-Rahman, Sherif Z. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States)]. E-mail: sabdelra@utmb.edu

    2006-03-20

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

  18. The Use of Animal Models for Cancer Chemoprevention Drug Development

    OpenAIRE

    2010-01-01

    Animal models currently are used to assess the efficacy of potential chemopreventive agents, including synthetic chemicals, chemical agents obtained from natural products and natural product mixtures. The observations made in these models as well as other data are then used to prioritize agents to determine which are qualified to progress to clinical chemoprevention trials. Organ specific animal models are employed to determine which agents or classes of agents are likely to be the most effec...

  19. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  20. Emerging Applications of Metabolomics in Studying Chemopreventive Phytochemicals

    OpenAIRE

    2013-01-01

    Phytochemicals from diet and herbal medicines are under intensive investigation for their potential use as chemopreventive agents to block and suppress carcinogenesis. Chemical diversity of phytochemicals, together with complex metabolic interactions between phytochemicals and biological system, can overwhelm the capacity of traditional analytical platforms, and thus pose major challenges in studying chemopreventive phytochemicals. Recent progresses in metabolomics have transformed it to beco...

  1. Spectroscopic characterization of lycopene extract from Lycopersicum esculentum (Tomato) and its evaluation as a chemopreventive agent against experimental hepatocarcinogenesis in mice.

    Science.gov (United States)

    Gupta, Prachi; Bansal, Mohinder Pal; Koul, Ashwani

    2013-03-01

    The present study was designed to characterize the lycopene extract (LycT) prepared from tomatoes (Lycopersicum esculentum) and then to evaluate its chemopreventive efficacy in N-diethylnitrosamine (NDEA)-induced experimental hepatocarcinogenesis in female Balb/c mice. The extraction of lycopene was carried out using hexane/acetone/ethanol as an extracting medium and then characterized by ultraviolet-visible, nuclear magnetic resonance and Fourier transform infrared spectroscopy. Chemopreventive efficacy of characterized LycT in vivo was evaluated in terms of hepatic tumour incidence, multiplicity, burden, hepatosomatic index and animal survival rate. Results indicated that average lycopene content of the tomato was 11.6-14 mg/kg tomato weight. Spectroscopic data confirmed the structural characteristics of lycopene in the extract. In the animal study, reduction in tumour incidence (42.05%), tumour burden (1.39) and tumour multiplicity (3.42) was observed upon LycT pretreatment to NDEA-treated animals. Histopathological analysis unravelled that the increased survival rate in LycT + NDEA-treated animals was due to the delay in the formation of aggressive tumour nodules. These observations indicate that lycopene seems to be an able candidate for chemoprevention in hepatocarcinogenesis resulting from NDEA insults.

  2. Chemoprevention of cancer: current evidence and future prospects [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Vassiliki Benetou

    2015-09-01

    Full Text Available Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories—hormonal, medications, diet-related agents, and vaccines—and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention.

  3. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  4. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells.

  5. Comet Assay in Cancer Chemoprevention.

    Science.gov (United States)

    Santoro, Raffaela; Ferraiuolo, Maria; Morgano, Gian Paolo; Muti, Paola; Strano, Sabrina

    2016-01-01

    The comet assay can be useful in monitoring DNA damage in single cells caused by exposure to genotoxic agents, such as those causing air, water, and soil pollution (e.g., pesticides, dioxins, electromagnetic fields) and chemo- and radiotherapy in cancer patients, or in the assessment of genoprotective effects of chemopreventive molecules. Therefore, it has particular importance in the fields of pharmacology and toxicology, and in both environmental and human biomonitoring. It allows the detection of single strand breaks as well as double-strand breaks and can be used in both normal and cancer cells. Here we describe the alkali method for comet assay, which allows to detect both single- and double-strand DNA breaks.

  6. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

    Science.gov (United States)

    Melchini, A; Costa, C; Traka, M; Miceli, N; Mithen, R; De Pasquale, R; Trovato, A

    2009-07-01

    Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (pinduction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

  7. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: jessig@mit.edu [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2015-01-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

  8. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    Science.gov (United States)

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  9. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

    Science.gov (United States)

    Bhatia, N; Agarwal, C; Agarwal, R

    2001-01-01

    Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

  10. Retinoids in lung cancer chemoprevention and treatment.

    Science.gov (United States)

    Toma, S; Raffo, P; Isnardi, L; Palumbo, R

    1999-01-01

    In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as

  11. Study of post-natal effect of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory action of indomethacin, voltaren, theophylline and epsilon-aminocaproic acid.

    Science.gov (United States)

    Alexandrov, V A; Bespalov, V G; Petrov, A S; Troyan, D N; Lidaks MYu

    1996-09-01

    The influence of the arachidonic acid metabolism inhibitors, indomethacin and voltaren; an inhibitor of phosphodiesterase activity, theophylline and the protease inhibitor epsilonaminocaproic acid (EACA) on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day after conception. Indomethacin and voltaren (20 p.p.m. in drinking water), theophylline (0.01% in diet) and EACA (1000 p.p.m. in drinking water) were given to the offspring throughout their post-natal life until all survivors were killed at 12 months. In the ENU-only control groups, 100% of the offspring developed tumors of brain, spinal cord, peripheral nervous system or kidneys, with a total average number of 3.1 tumors per rat. The most marked inhibitory effect was exerted by theophylline, which significantly decreased the incidence and multiplicity of total tumors, and at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys). It also prolonged average survival time of the offspring. Indomethacin and voltaren significantly decreased total tumor incidence and multiplicity and brain tumor incidence and multiplicity. Indomethacin also decreased kidney tumor multiplicity and voltaren diminished spinal cord tumor multiplicity. EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the incidence of brain tumors. These chemopreventive agents decreased tumor incidences 20-33% and tumor multiplicities 1.4-2.7 times, compared with the ENU-only controls.

  12. Emerging applications of metabolomics in studying chemopreventive phytochemicals.

    Science.gov (United States)

    Wang, Lei; Chen, Chi

    2013-10-01

    Phytochemicals from diet and herbal medicines are under intensive investigation for their potential use as chemopreventive agents to block and suppress carcinogenesis. Chemical diversity of phytochemicals, together with complex metabolic interactions between phytochemicals and biological system, can overwhelm the capacity of traditional analytical platforms, and thus pose major challenges in studying chemopreventive phytochemicals. Recent progresses in metabolomics have transformed it to become a robust systems biology tool, suitable for examining both chemical and biochemical events that contribute to the cancer prevention activities of plant preparations or their bioactive components. This review aims to discuss the technical platform of metabolomics and its existing and potential applications in chemoprevention research, including identifying bioactive phytochemicals in plant extracts, monitoring phytochemical exposure in humans, elucidating biotransformation pathways of phytochemicals, and characterizing the effects of phytochemicals on endogenous metabolism and cancer metabolism.

  13. Keap1 eye on the target: chemoprevention of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Melinda Sue YATES; Thomas Wells KENSLER

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide,causing nearly 600000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is respon-sible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However,complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practi-cal strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both expo-sures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabo-lites can be used as biomarkers to evaluate modulation of aflatoxin disposition.Modulation of aflatoxin disposition can be achieved through induction of conju-gating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap 1)-NF-E2-related factor 2(Nrf2)-antioxi-dant response element (ARE) signaling, making this pathway an important mo-lecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids.Furthermore, clinical interventions have shown that inducers of Keap 1-Nrf2-ARE signaling increase cytoprotective enzyme expression, resulting in modula-tion of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive

  14. Chemoprevention of prostate cancer with nutrients and supplements

    Directory of Open Access Journals (Sweden)

    Van Poppel H

    2011-04-01

    Full Text Available Hendrik Van Poppel1, Bertrand Tombal21Department of Urology, University Hospital, KU Leuven, Leuven, Belgium; 2Service d’Urologie, Cliniques Universtaires Saint Luc, Brussels, BelgiumAbstract: As the adult population is increasing, prostate cancer (PCa will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic.Keywords: alpha-tocopherol, chemoprevention, isoflavones, lycopene, polyphenols, prostate cancer, selenium

  15. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  16. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical

    Institute of Scientific and Technical Information of China (English)

    Yuesheng ZHANG; Li TANG

    2007-01-01

    Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including suscep-tibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis.We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention.

  17. Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons

    OpenAIRE

    2013-01-01

    Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert...

  18. Evidence supporting the conceptual framework of cancer chemoprevention in canines

    OpenAIRE

    Kondratyuk, Tamara P.; Julie Ann Luiz Adrian; Brian Wright; Eun-Jung Park; van Breemen, Richard B.; Morris, Kenneth R.; Pezzuto, John M.

    2016-01-01

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-induci...

  19. Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

    Directory of Open Access Journals (Sweden)

    Mohammad Fahad Ullah

    2015-07-01

    Full Text Available The International Agency for Research on Cancer (IARC in its latest World Cancer Report (2014 has projected the increase in the global cancer burden from 14 million (2012 to 22 million incidence annually within the next two decades. Such statistics warrant a collaborative engagement of conventional and complementary and alternative therapies to contain and manage cancer. In recent years, there has been a shift in the cancer chemoprevention paradigm with a significant focus turning towards bioactive components of human diets for their anticancer properties. Since diet is an integral part of lifestyle and given that an estimated one third of human cancers are believed to be preventable though appropriate lifestyle modification including dietary habits, the current shift in the conventional paradigm assumes significance. Several epidemiological studies have indicated that consumption of broccoli is associated with a lower risk of cancer incidence including breast, prostate, lung, stomach and colon cancer. The edible plant belonging to the family of cruciferae such as broccoli is a rich source of glucoraphanin, a precursor of isothiocyanate sulforaphane which is considered to be a potent anti-cancer agent. Plant-based dietary agents such as sulforaphane mimic chemotherapeutic drugs such as vorinostat, possessing histone deacetylase inhibition activity. Evidence from epidemiological and experimental studies have emerged, enhancing the clinical plausibility and translational value of sulforaphane in cancer chemoprevention. The present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.

  20. The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

    Science.gov (United States)

    Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif

    2016-01-01

    Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment. PMID:27051643

  1. Nicotinamide for skin cancer chemoprevention.

    Science.gov (United States)

    Damian, Diona L

    2017-03-20

    Nicotinamide (vitamin B3 ) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation-induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high-risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population.

  2. Evidence supporting the conceptual framework of cancer chemoprevention in canines.

    Science.gov (United States)

    Kondratyuk, Tamara P; Adrian, Julie Ann Luiz; Wright, Brian; Park, Eun-Jung; van Breemen, Richard B; Morris, Kenneth R; Pezzuto, John M

    2016-05-24

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of "man's best friend".

  3. Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets.

    Science.gov (United States)

    Rajendran, Peramaiyan; Rengarajan, Thamaraiselvan; Nandakumar, Natarajan; Divya, H; Nishigaki, Ikuo

    2015-02-01

    A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

  4. [Chemoprevention of tobacco-related lung cancer by cruciferous vegetable].

    Science.gov (United States)

    Balcerek, Maciej

    2007-01-01

    Lung cancer is the most common malignant disease in the world and the major cause of death from cancers. Around 80-90% of all human lung cancers are related to cigarette smoke. Tobacco smoke contains at least 60 carcinogens capable of causing tumors, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and polycyclic aromatic hydrocarbons (PAH) are among the most prominent pulmonary carcinogens. Prevention is the most effective way to reduce lung cancer mortality. Chemoprevention is a cancer preventive strategy to inhibit, delay or reverse carcinogenesis using naturally occurring or synthetic chemical agents. A number of epidemiological studies have shown an inverse relationship between cruciferous vegetable consumption and cancer, especially those of lung and stomach. Crucifers, such as broccoli, cauliflower, brussel sprouts and cabbage, contain a family of secondary plant metabolites known as glucosinolates, which are unique to these vegetables. Upon hydrolysis, glucosinolates yield a number of breakdown products, mostly isothiocyanates, with supposed chemopreventive properties, as shown in animal experiments. It appears that significant portion of the chemopreventive effects of isothiocyanates may be associated with the inhibition of the metabolic activation of carcinogens by cytochrome P450s (Phase I), coupled with strong induction of phase II of detoxifying enzymes.

  5. CAED Document Repository

    Data.gov (United States)

    U.S. Environmental Protection Agency — Compliance Assurance and Enforcement Division Document Repository (CAEDDOCRESP) provides internal and external access of Inspection Records, Enforcement Actions, and...

  6. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  7. The Role of Nutraceuticals in Chemoprevention and Chemotherapy and Their Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Sabita N. Saldanha

    2012-01-01

    Full Text Available The genesis of cancer is often a slow process and the risk of developing cancer increases with age. Altering a diet that includes consumption of beneficial phytochemicals can influence the balance and availability of dietary chemopreventive agents. In chemopreventive approaches, foods containing chemicals that have anticancer properties can be supplemented in diets to prevent precancerous lesions from occurring. This necessitates further understanding of how phytochemicals can potently maintain healthy cells. Fortunately there is a plethora of plant-based phytochemicals although few of them are well studied in terms of their application as cancer chemopreventive and therapeutic agents. In this analysis we will examine phytochemicals that have strong chemopreventive and therapeutic properties in vitro as well as the design and modification of these bioactive compounds for preclinical and clinical applications. The increasing potential of combinational approaches using more than one bioactive dietary compound in chemoprevention or cancer therapy will also be evaluated. Many novel approaches to cancer prevention are on the horizon, several of which are showing great promise in saving lives in a cost-effective manner.

  8. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

    Directory of Open Access Journals (Sweden)

    Nur Özten-Kandas

    2011-01-01

    Full Text Available Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1 Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2 chemoprevention drugs including agents interfering with androgen action, and (3 antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.

  9. Endotoxin and cancer chemo-prevention.

    Science.gov (United States)

    Mastrangelo, Giuseppe; Fadda, Emanuela; Cegolon, Luca

    2013-10-01

    Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer.

  10. Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention.

    Science.gov (United States)

    Lissa, Delphine; Senovilla, Laura; Rello-Varona, Santiago; Vitale, Ilio; Michaud, Mickaël; Pietrocola, Federico; Boilève, Alice; Obrist, Florine; Bordenave, Chloé; Garcia, Pauline; Michels, Judith; Jemaà, Mohamed; Kepp, Oliver; Castedo, Maria; Kroemer, Guido

    2014-02-25

    Tetraploidy constitutes a genomically metastable state that can lead to aneuploidy and genomic instability. Tetraploid cells are frequently found in preneoplastic lesions, including intestinal cancers arising due to the inactivation of the tumor suppressor adenomatous polyposis coli (APC). Using a phenotypic screen, we identified resveratrol as an agent that selectively reduces the fitness of tetraploid cells by slowing down their cell cycle progression and by stimulating the intrinsic pathway of apoptosis. Selective killing of tetraploid cells was observed for a series of additional agents that indirectly or directly stimulate AMP-activated protein kinase (AMPK) including salicylate, whose chemopreventive action has been established by epidemiological studies and clinical trials. Both resveratrol and salicylate reduced the formation of tetraploid or higher-order polyploid cells resulting from the culture of human colon carcinoma cell lines or primary mouse epithelial cells lacking tumor protein p53 (TP53, best known as p53) in the presence of antimitotic agents, as determined by cytofluorometric and videomicroscopic assays. Moreover, oral treatment with either resveratrol or aspirin, the prodrug of salicylate, repressed the accumulation of tetraploid intestinal epithelial cells in the Apc(Min/+) mouse model of colon cancer. Collectively, our results suggest that the chemopreventive action of resveratrol and aspirin involves the elimination of tetraploid cancer cell precursors.

  11. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  12. Prostate cancer chemoprevention in men of African descent: current state of the art and opportunities for future research.

    Science.gov (United States)

    Chornokur, Ganna; Kumar, Nagi B

    2013-08-01

    Prostate cancer is the most frequently diagnosed malignancy in men. However, African American/Black men are 60 % more likely to be diagnosed with and 2.4 times more likely to die from prostate cancer, compared to Non-Hispanic White men. Despite the increased burden of this malignancy, no evidence-based recommendation regarding prostate cancer screening exists for the high-risk population. Moreover, in addition to screening and detection, African American men may constitute a prime population for chemoprevention. Early detection and chemoprevention may thus represent an integral part of prostate cancer control in this population. Importantly, recent research has elucidated biological differences in the prostate tumors of African American compared to European American men. The latter may enable a more favorable response in African American men to specific chemopreventive agents that target relevant signal transduction pathways. Based on this evolving evidence, the aims of this review are threefold. First, we aim to summarize the biological differences that were reported in the prostate tumors of African American and European American men. Second, we will review the single- and multi-target chemopreventive agents placing specific emphasis on the pathways implicated in prostate carcinogenesis. And lastly, we will discuss the most promising nutraceutical chemopreventive compounds. Our review underscores the promise of chemoprevention in prostate cancer control, as well as provides justification for further investment in this filed to ultimately reduce prostate cancer morbidity and mortality in this high-risk population of African American men.

  13. NIA Aging Cell Repository

    Data.gov (United States)

    Federal Laboratory Consortium — To facilitate aging research on cells in culture, the NIA provides support for the NIA Aging Cell Repository, located at the Coriell Institute for Medical Research...

  14. NIDDK Central Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  15. NIH Data Sharing Repositories

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of NIH-supported repositories that accept submissions of appropriate scientific research data from biomedical researchers. It includes resources that...

  16. Plant phytochemicals as epigenetic modulators: role in cancer chemoprevention.

    Science.gov (United States)

    Thakur, Vijay S; Deb, Gauri; Babcook, Melissa A; Gupta, Sanjay

    2014-01-01

    In recent years, "nutri-epigenetics," which focuses on the influence of dietary agents on epigenetic mechanism(s), has emerged as an exciting novel area in epigenetics research. Targeting of aberrant epigenetic modifications has gained considerable attention in cancer chemoprevention research because, unlike genetic changes, epigenetic alterations are reversible and occur during early carcinogenesis. Aberrant epigenetic mechanisms, such as promoter DNA methylation, histone modifications, and miRNA-mediated post-transcriptional alterations, can silence critical tumor suppressor genes, such as transcription factors, cell cycle regulators, nuclear receptors, signal transducers, and apoptosis-inducing and DNA repair gene products, and ultimately contribute to carcinogenesis. In an effort to identify and develop anticancer agents which cause minimal harm to normal cells while effectively killing cancer cells, a number of naturally occurring phytochemicals in food and medicinal plants have been investigated. This review highlights the potential role of plant-derived phytochemicals in targeting epigenetic alterations that occur during carcinogenesis, by modulating the activity or expression of DNA methyltransferases, histone modifying enzymes, and miRNAs. We present in detail the epigenetic mode of action of various phytochemicals and discuss their potential as safe and clinically useful chemopreventive strategies.

  17. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-09-01

    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  18. Repository seals requirements study

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-03

    The Yucca Mountain Site Characterization Project, managed by the Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) is conducting investigations to support the Viability Assessment and the License Application for a high-level nuclear waste repository at Yucca Mountain, Nevada. The sealing subsystem is part of the Yucca Mountain Waste Isolation System. The Yucca Mountain Site Characterization Project is currently evaluating the role of the sealing subsystem (shaft, ramp and exploratory borehole seals) in achieving the overall performance objectives for the Waste Isolation System. This report documents the results of those evaluations. This report presents the results of a repository sealing requirements study. Sealing is defined as the permanent closure of the shafts, ramps, and exploratory boreholes. Sealing includes those components that would reduce potential inflows above the repository, or that would divert flow near the repository horizon to allow vertical infiltration to below the repository. Sealing of such features as emplacement drifts was not done in this study because the current capability to calculate fracture flow into the drifts is not sufficiently mature. The objective of the study is to provide water or air flow performance based requirements for shafts, ramps, and exploratory boreholes located near the repository. Recommendations, as appropriate, are provided for developing plans, seals component testing, and other studies relating to sealing.

  19. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    Science.gov (United States)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  20. Review paper: Cancer chemopreventive compounds and canine cancer.

    Science.gov (United States)

    Baek, S J; McEntee, M F; Legendre, A M

    2009-07-01

    Canine cancer has become more prevalent in recent years because of increased life expectancy and greater attention to the health of pets. The range of cancers seen in dogs is as diverse as that in human patients, and despite more intensive therapeutic interventions, fatality rates remain unacceptably high in both species. Chemoprevention is therefore an important means of confronting this disease. Because domestic pets share our environment, greater cross-application and study of the protumorigenic and antitumorigenic factors in our shared environment will benefit all species, leading to the development of new families of less toxic antitumorigenic compounds based on novel and established molecular targets. Currently, the most interesting cancer preventive agents are nonsteroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor-gamma ligands, and dietary compounds. This article provides an overview of what is known about how these agents affect molecular signaling in neoplastic disease, with reference to reported application and/or study in dogs where available.

  1. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property [v1; ref status: indexed, http://f1000r.es/15s

    Directory of Open Access Journals (Sweden)

    Asfar S Azmi

    2013-06-01

    Full Text Available “Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  2. Chemopreventive effect of Lagenaria siceraria in two stages DMBA plus croton oil induced skin papillomagenesis.

    Science.gov (United States)

    Kumar, Navneet; Kale, Raosaheb K; Tiku, Ashu B

    2013-01-01

    Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer.

  3. Trust in Digital Repositories

    Directory of Open Access Journals (Sweden)

    Elizabeth Yakel

    2013-06-01

    Full Text Available ISO 16363:2012, Space Data and Information Transfer Systems - Audit and Certification of Trustworthy Digital Repositories (ISO TRAC, outlines actions a repository can take to be considered trustworthy, but research examining whether the repository’s designated community of users associates such actions with trustworthiness has been limited. Drawing from this ISO document and the management and information systems literatures, this paper discusses findings from interviews with 66 archaeologists and quantitative social scientists. We found similarities and differences across the disciplines and among the social scientists. Both disciplinary communities associated trust with a repository’s transparency. However, archaeologists mentioned guarantees of preservation and sustainability more frequently than the social scientists, who talked about institutional reputation. Repository processes were also linked to trust, with archaeologists more frequently citing metadata issues and social scientists discussing data selection and cleaning processes. Among the social scientists, novices mentioned the influence of colleagues on their trust in repositories almost twice as much as the experts. We discuss the implications our findings have for identifying trustworthy repositories and how they extend the models presented in the management and information systems literatures.

  4. Ellagitannins in Cancer Chemoprevention and Therapy

    Directory of Open Access Journals (Sweden)

    Tariq Ismail

    2016-05-01

    Full Text Available It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET, polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties.

  5. Comparing Repository Types - Challenges and barriers for subject-based repositories, research repositories, national repository systems and institutional repositories in serving scholarly communication

    CERN Document Server

    Armbruster, Chris

    2010-01-01

    After two decades of repository development, some conclusions may be drawn as to which type of repository and what kind of service best supports digital scholarly communication, and thus the production of new knowledge. Four types of publication repository may be distinguished, namely the subject-based repository, research repository, national repository system and institutional repository. Two important shifts in the role of repositories may be noted. With regard to content, a well-defined and high quality corpus is essential. This implies that repository services are likely to be most successful when constructed with the user and reader uppermost in mind. With regard to service, high value to specific scholarly communities is essential. This implies that repositories are likely to be most useful to scholars when they offer dedicated services supporting the production of new knowledge. Along these lines, challenges and barriers to repository development may be identified in three key dimensions: a) identific...

  6. The role of aspirin in colorectal cancer chemoprevention.

    Science.gov (United States)

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity.

  7. Carnosol: A Phenolic Diterpene With Cancer Chemopreventive Potential

    Science.gov (United States)

    Chun, Kyung-Soo; Kundu, Juthika; Chae, In Gyeong; Kundu, Joydeb Kumar

    2014-01-01

    Cancer is an unbeaten health challenge for the humankind. After striving for decades to find a cancer cure, attention has now been shifted to reduce the morbidity and mortality from cancer by halting the course of tumor development. Numerous bioactive phytochemicals, especially those present in edible and non-edible plant species, have been reported to reduce the risk of many cancers. Multiple lines of evidence suggest that carnosol, a phenolic diterpene present in rosemary (Rosmarinus officinalis L.), holds the promise of preventing certain types of cancer. A remarkable progress has been made in delineating the biochemical mechanisms underlying the chemopreventive effects of carnosol. Results from in vitro cell culture studies as well as animal model experiments have revealed that carnosol inhibits experimentally induced carcinogenesis and exhibits potent anti-oxidative, anti-inflammatory, antiproliferative and apoptosis inducing properties. Moreover, carnosol enhances the sensitivity of chemoresistant cancer cells to chemotherapeutic agents. The purpose of this review is to shed light on the detailed mechanistic aspects of cancer chemoprevention with carnosol. PMID:25337578

  8. The Computational Materials Repository

    DEFF Research Database (Denmark)

    Landis, David D.; Hummelshøj, Jens S.; Nestorov, Svetlozar

    2012-01-01

    The possibilities for designing new materials based on quantum physics calculations are rapidly growing, but these design efforts lead to a significant increase in the amount of computational data created. The Computational Materials Repository (CMR) addresses this data challenge and provides...... a software infrastructure that supports the collection, storage, retrieval, analysis, and sharing of data produced by many electronic-structure simulators....

  9. Corticotropin, Repository Injection

    Science.gov (United States)

    H.P. Acthar Gel® ... Corticotropin repository injection comes as a long acting gel to inject under the skin or into a ... prescription and nonprescription medications, vitamins, nutritional supplements, or herbal products you are taking or plan to take. ...

  10. CRIS and Institutional Repositories

    Directory of Open Access Journals (Sweden)

    A Asserson

    2010-04-01

    Full Text Available CRIS (Current Research Information Systems provide researchers, research managers, innovators, and others with a view over the research activity of a domain. IRs (institutional repositories provide a mechanism for an organisation to showcase through OA (open access its intellectual property. Increasingly, organizations are mandating that their employed researchers deposit peer-reviewed published material in the IR. Research funders are increasingly mandating that publications be deposited in an open access repository: some mandate a central (or subject-based repository, some an IR. In parallel, publishers are offering OA but replacing subscription-based access with author (or author institution payment for publishing. However, many OA repositories have metadata based on DC (Dublin Core which is inadequate; a CERIF (Common-European Research Information Format CRIS provides metadata describing publications with formal syntax and declared semantics thus facilitating interoperation or homogeneous access over heterogeneous sources. The formality is essential for research output metrics, which are increasingly being used to determine future funding for research organizations.

  11. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  12. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence.

    Science.gov (United States)

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J Luis

    2016-08-09

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

  13. Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies.

    Science.gov (United States)

    Pathak, S K; Sharma, R A; Steward, W P; Mellon, J K; Griffiths, T R L; Gescher, A J

    2005-01-01

    Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. Oxidative stress may be linked to the effects of androgens, anti-oxidant systems and the pre-malignant condition, high-grade prostatic intraepithelial neoplasia. Cyclooxygenase-2 activity has been linked with prostate carcinogenesis. Evidence suggests that oxidative stress and cyclo-oxygenase-2 activity may be mechanistically linked. Agents such as anti-oxidants and cyclo-oxgenase-2 inhibitors may be of value in the chemoprevention of prostate cancer. The feasibility of intervention with such agents will depend on the development and validation of biomarkers for clinical trials, particularly markers of oxidative damage caused by reactive oxygen species (ROS). A greater understanding of the molecular events associated with oxidative stress will enhance the development of such biomarkers and should result in better strategies for the chemoprevention of prostate cancer.

  14. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development.

    Science.gov (United States)

    Chung, Min-Yu; Lim, Tae Gyu; Lee, Ki Won

    2013-02-21

    Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual's lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers.

  15. Population Pharmacokinetic Model for Cancer Chemoprevention With Sulindac in Healthy Subjects

    OpenAIRE

    Berg, Alexander K.; Mandrekar, Sumithra J.; Ziegler, Katie L. Allen; Carlson, Elsa C.; Szabo, Eva; Ames, Mathew M.; Boring, Daniel; Limburg, Paul J.; Reid, Joel M.

    2013-01-01

    Sulindac is a prescription-based non-steroidal anti-inflammatory drug (NSAID) that continues to be actively investigated as a candidate cancer chemoprevention agent. To further current understanding of sulindac bioavailability, metabolism, and disposition, we developed a population pharmacokinetic model for the parent compound and its active metabolites, sulindac sulfide, and exisulind. This analysis was based on data from 24 healthy subjects who participated in a bioequivalence study compari...

  16. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

    Science.gov (United States)

    Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

    2015-01-01

    Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150-200 nm average diameter NPs were prepared by the double emulsion-solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA-PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

  17. Multitargeted Low-Dose GLAD Combination Chemoprevention: A Novel and Promising Approach to Combat Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2013-05-01

    Full Text Available Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APCMin/+ mice. Six-week-old wild-type and APCMin/+ mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80–83%, P 95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APCMin/+ mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.

  18. Publishers and repositories

    CERN Document Server

    CERN. Geneva

    2007-01-01

    The impact of self-archiving on journals and publishers is an important topic for all those involved in scholarly communication. There is some evidence that the physics arXiv has had no impact on physics journals, while 'economic common sense' suggests that some impact is inevitable. I shall review recent studies of librarian attitudes towards repositories and journals, and place this in the context of IOP Publishing's experiences with arXiv. I shall offer some possible reasons for the mis-match between these perspectives and then discuss how IOP has linked with arXiv and experimented with OA publishing. As well as launching OA journals we have co-operated with Cornell and the arXiv on Eprintweb.org, a platform that offers new features to repository users. View Andrew Wray's biography

  19. Distributed Web Service Repository

    Directory of Open Access Journals (Sweden)

    Piotr Nawrocki

    2015-01-01

    Full Text Available The increasing availability and popularity of computer systems has resulted in a demand for new, language- and platform-independent ways of data exchange. That demand has in turn led to a significant growth in the importance of systems based on Web services. Alongside the growing number of systems accessible via Web services came the need for specialized data repositories that could offer effective means of searching of available services. The development of mobile systems and wireless data transmission technologies has allowed the use of distributed devices and computer systems on a greater scale. The accelerating growth of distributed systems might be a good reason to consider the development of distributed Web service repositories with built-in mechanisms for data migration and synchronization.

  20. Pharmacoproteomic analysis reveals that metapristone (RU486 metabolite) intervenes E-cadherin and vimentin to realize cancer metastasis chemoprevention.

    Science.gov (United States)

    Yu, Suhong; Yan, Cuicui; Yang, Xingtian; He, Sudang; Liu, Jian; Qin, Chongtao; Huang, Chuanzhong; Lu, Yusheng; Tian, Zhongping; Jia, Lee

    2016-03-02

    Metapristone is the most predominant biological active metabolite of mifepristone, and being developed as a novel cancer metastasis chemopreventive agent by us. Despite its prominent metastasis chemopreventive effect, the underlying mechanism remains elusive. Our study, for the first time, demonstrated that metapristone had the ability to prevent breast cancer cells from migration, invasion, and interfere with their adhesion to endothelial cells. To explore the underlying mechanism of metapristone, we employed the iTRAQ technique to assess the effect of metapristone on MDA-MB-231 cells. In total, 5,145 proteins were identified, of which, 311 proteins showed significant differences in metapristone-treated cells compared to the control group (P-value metastasis chemoprevention is through intervening the EMT-related signaling pathways.

  1. Staged Repository Development Programmes

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, T

    2003-10-01

    Programs to manage and ultimately dispose of high-level radioactive wastes are unique from scientific and technological as well as socio-political aspects. From a scientific and technological perspective, high-level radioactive wastes remain potentially hazardous for geological time periods-many millennia-and scientific and technological programs must be put in place that result in a system that provides high confidence that the wastes will be isolated from the accessible environment for these many thousands of years. Of course, ''proof'' in the classical sense is not possible at the outset, since the performance of the system can only be known with assurance, if ever, after the waste has been emplaced for those geological time periods. Adding to this challenge, many uncertainties exist in both the natural and engineered systems that are intended to isolate the wastes, and some of the uncertainties will remain regardless of the time and expense in attempting to characterize the system and assess its performance. What was perhaps underappreciated in the early days of waste management and repository program development were the unique and intense reactions that the institutional, political, and public bodies would have to repository program development, particularly in programs attempting to identify and then select sites for characterization, design, licensing, and ultimate development. Reactions in most nations were strong, focused, unrelenting, and often successful in hindering, derailing, and even stopping national repository programs. The reasons for such reactions and the measures to successfully respond to them are still evolving and continue to be the focus of many national program and political leaders. Adaptive Staging suggests an approach to repository program development that reflects the unique challenges associated with the disposal of high-level radioactive waste. The step-wise, incremental, learn-as-you-go approach is intended to

  2. Repository performance confirmation.

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Francis D.

    2011-09-01

    Repository performance confirmation links the technical bases of repository science and societal acceptance. This paper explores the myriad aspects of what has been labeled performance confirmation in U.S. programs, which involves monitoring as a collection of distinct activities combining technical and social significance in radioactive waste management. This paper is divided into four parts: (1) A distinction is drawn between performance confirmation monitoring and other testing and monitoring objectives; (2) A case study illustrates confirmation activities integrated within a long-term testing and monitoring strategy for Yucca Mountain; (3) A case study reviews compliance monitoring developed and implemented for the Waste Isolation Pilot Plant; and (4) An approach for developing, evaluating and implementing the next generation of performance confirmation monitoring is presented. International interest in repository monitoring is exhibited by the European Commission Seventh Framework Programme 'Monitoring Developments for Safe Repository Operation and Staged Closure' (MoDeRn) Project. The MoDeRn partners are considering the role of monitoring in a phased approach to the geological disposal of radioactive waste. As repository plans advance in different countries, the need to consider monitoring strategies within a controlled framework has become more apparent. The MoDeRn project pulls together technical and societal experts to assimilate a common understanding of a process that could be followed to develop a monitoring program. A fundamental consideration is the differentiation of confirmation monitoring from the many other testing and monitoring activities. Recently, the license application for Yucca Mountain provided a case study including a technical process for meeting regulatory requirements to confirm repository performance as well as considerations related to the preservation of retrievability. The performance confirmation plan developed as part

  3. Towards Interoperable Preservation Repositories: TIPR

    Directory of Open Access Journals (Sweden)

    Priscilla Caplan

    2010-07-01

    Full Text Available Towards Interoperable Preservation Repositories (TIPR is a project funded by the Institute of Museum and Library Services to create and test a Repository eXchange Package (RXP. The package will make it possible to transfer complex digital objects between dissimilar preservation repositories.  For reasons of redundancy, succession planning and software migration, repositories must be able to exchange copies of archival information packages with each other. Every different repository application, however, describes and structures its archival packages differently. Therefore each system produces dissemination packages that are rarely understandable or usable as submission packages by other repositories. The RXP is an answer to that mismatch. Other solutions for transferring packages between repositories focus either on transfers between repositories of the same type, such as DSpace-to-DSpace transfers, or on processes that rely on central translation services.  Rather than build translators between many dissimilar repository types, the TIPR project has defined a standards-based package of metadata files that can act as an intermediary information package, the RXP, a lingua franca all repositories can read and write.

  4. Pancreatic cancer chemoprevention by phytochemicals.

    Science.gov (United States)

    Boreddy, Srinivas Reddy; Srivastava, Sanjay K

    2013-06-28

    Pancreatic cancer is fourth leading cause of cancer-related deaths in the United States of America. In spite of recent advances in the current therapeutic modalities such as surgery, radiation and chemotherapy patients, the average five year survival rate remains still less than 5%. Recently, compounds from natural sources receive ample of attention as anti-cancer agents. Many epidemiological studies published over the past few decades provide a strong correlation between consumption of vegetables, fruits or plant derived products and reduced incidence of cancer. The present review focuses on the potential antitumor effects of various natural products.

  5. Anti-inflammatory phytochemicals for chemoprevention of colon cancer.

    Science.gov (United States)

    Madka, Venkateshwar; Rao, Chinthalapally V

    2013-06-01

    Every year more than a million new cancer cases and 600,000 deaths are reported world-wide. Colorectal cancer is the fourth most commonly occurring and second leading cause of cancer deaths in the United States. Significant progress has been made in understanding colorectal cancer through epidemiological, laboratory and clinical studies. Development of metastatic adenocarcinomas is a multistage process occurring over several years during which multiple genetic alterations and pathophysiological changes are associated. Colorectal cancer can be prevented if the transformation of normal colonic crypt cells to malignant can be halted or reversed. Some of the key molecules that are altered significantly and play important roles in colorectal tumor progression are associated with inflammation. Since chronic inflammation is now recognized as a potential risk factor for tumor development, targeting inflammatory pathways has proven effective in preventing formation of colonic tumors and their malignant progression in both preclinical and clinical studies. Synthetic non-steroidal anti-inflammatory drugs (NSAIDS) have been identified as potential colorectal cancer chemopreventive agents; however, most of these synthetic agents are associated with unwanted and sometimes fatal side effects. There is mounting evidence in support of the efficacy of naturally-occurring phytochemicals possessing anti-inflammatory activity. In this review we discuss key inflammatory pathways associated with colorectal cancer and promising naturally-occurring phytochemicals as anti-inflammatory agents for the prevention and treatment of colorectal cancer.

  6. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action

    Directory of Open Access Journals (Sweden)

    A A Oyagbemi

    2010-01-01

    Full Text Available Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae. Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB, activator protein 1 (AP-1, and signal transducer and activator of transcription (STAT3 signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms ′capsaicin′ and ′anticancer′ citations, relevant to anticancer properties of capsaicin.

  7. NASA Biological Specimen Repository

    Science.gov (United States)

    McMonigal, K. A.; Pietrzyk, R. A.; Sams, C. F.; Johnson, M. A.

    2010-01-01

    The NASA Biological Specimen Repository (NBSR) was established in 2006 to collect, process, preserve and distribute spaceflight-related biological specimens from long duration ISS astronauts. This repository provides unique opportunities to study longitudinal changes in human physiology spanning may missions. The NBSR collects blood and urine samples from all participating ISS crewmembers who have provided informed consent. These biological samples are collected once before flight, during flight scheduled on flight days 15, 30, 60, 120 and within 2 weeks of landing. Postflight sessions are conducted 3 and 30 days after landing. The number of in-flight sessions is dependent on the duration of the mission. Specimens are maintained under optimal storage conditions in a manner that will maximize their integrity and viability for future research The repository operates under the authority of the NASA/JSC Committee for the Protection of Human Subjects to support scientific discovery that contributes to our fundamental knowledge in the area of human physiological changes and adaptation to a microgravity environment. The NBSR will institute guidelines for the solicitation, review and sample distribution process through establishment of the NBSR Advisory Board. The Advisory Board will be composed of representatives of all participating space agencies to evaluate each request from investigators for use of the samples. This process will be consistent with ethical principles, protection of crewmember confidentiality, prevailing laws and regulations, intellectual property policies, and consent form language. Operations supporting the NBSR are scheduled to continue until the end of U.S. presence on the ISS. Sample distribution is proposed to begin with selections on investigations beginning in 2017. The availability of the NBSR will contribute to the body of knowledge about the diverse factors of spaceflight on human physiology.

  8. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2013-07-01

    Full Text Available Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

  9. Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Albert Cabrera

    2014-05-01

    Full Text Available The objective of the present review is to study the relationship between flavonoids and lung cancer, proposing that their regular consumption in Western diets could be beneficial for protecting patients against lung cancer. An extensive search of the scientific literature was performed in the following electronic specialized databases (PubMed central (PMC-NBCI, Elsevier Journal, SciELO Spain, Scirus, Science Direct, including studies in animals, cells, and humans, in order to establish the effect of flavonoids in the prevention and development of lung cancer. Although in vitro and animal studies show the potential ability of flavonoids to act against different types of cancers, especially against lung cancers, the diverse results reported within epidemiological studies, together with the lack of experiments in humans, are the major factors in limiting making dietary recommendations based on scientific evidence for the management of patients with lung cancer. Therefore, the authors of the present study recommend following the dietary health practice guidelines which promotes the consumption of food enriched in flavonoids and reflects the current state of knowledge of an effective and appropriate diet in lung cancer patients.Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2:91-92Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

  10. Influence analysis of Github repositories.

    Science.gov (United States)

    Hu, Yan; Zhang, Jun; Bai, Xiaomei; Yu, Shuo; Yang, Zhuo

    2016-01-01

    With the support of cloud computing techniques, social coding platforms have changed the style of software development. Github is now the most popular social coding platform and project hosting service. Software developers of various levels keep entering Github, and use Github to save their public and private software projects. The large amounts of software developers and software repositories on Github are posing new challenges to the world of software engineering. This paper tries to tackle one of the important problems: analyzing the importance and influence of Github repositories. We proposed a HITS based influence analysis on graphs that represent the star relationship between Github users and repositories. A weighted version of HITS is applied to the overall star graph, and generates a different set of top influential repositories other than the results from standard version of HITS algorithm. We also conduct the influential analysis on per-month star graph, and study the monthly influence ranking of top repositories.

  11. Trusted Data Repositories

    Science.gov (United States)

    Giaretta, D.

    2008-08-01

    Data is valuable, expensive to create, and may be impossible to re-create, so who can be trusted to look after it in the long term? This is a question which applies to all the types of digital data on which most astronomical research, and much of the rest of civilisation, depends. This talk will outline the work which has been, and continues to be, carried out to provide an answer to the question of how to judge whether any given data repository is up to the task and deserves to be funded. The OAIS Reference Model (ISO 14721) forms the basis of most serious work on digital preservation and the aim of the work described here is to build on OAIS to create an international standard on which an accreditation and certification process can be based. The talk will touch on some of the fundamental ideas about preservation of digital objects and on ways to detect preservation snakeoil salesmen.

  12. [Colorectal adenomas: postpolypectomy surveillance strategies and chemoprevention].

    Science.gov (United States)

    Castells, Antoni

    2008-10-01

    Colorectal adenomas are the most fully characterized premalignant lesions in the development of colorectal cancer. Consequently, the identification and resolution of these lesions, as well as the follow-up of affected patients, are a priority in the prevention of this neoplasm. The studies presented in the annual meeting of the American Gastroenterological Association 2008 show that the results of current surveillance strategies can be improved with a view to reducing the rate of interval neoplasia. Improvement of these results includes optimization of the endoscopic technique (colonic preparation, cecal intubation, withdrawal time, etc.) as well as the incorporation of new diagnostic methods and the possible administration of chemopreventive drugs.

  13. Chemopreventive effect of Curcuma longa Linn on liver pathology in HBx transgenic mice.

    Science.gov (United States)

    Kim, Jungsun; Ha, Hye-Lin; Moon, Hyung-Bae; Lee, Yeon-Weol; Cho, Chong-Kwan; Yoo, Hwa-Seung; Yu, Dae-Yeul

    2011-06-01

    Unlike other forms of hepatocellular carcinoma (HCC), HCC induced by hepatitis B virus (HBV) infection shows a poor prognosis after conventional therapies. HBV induces liver cirrhosis and HCC. Many researchers have made efforts to find new substances that suppress the activity of HBV. Curcuma longa Linn (CLL) has been used for traditional medicine and food in Asia, especially in India, and has shown chemopreventive effects in a HBV-related in vitro model. This in vivo study was designed to seek the chemopreventive effects of CLL and its mechanisms. CLL mixture concentrated with dextrose water by boiling was lyophilized. CLL extracts were administrated to HBV X protein (HBx) transgenic mice aged 4 weeks for 2 to 4 weeks and aged 6 months for 3 months. After administration, histological changes in the liver tissue and expression of HBx-related genes were investigated. CLL-treated mice showed less visceral fat, a smaller liver/body weight ratio and delayed liver pathogenesis. Proliferating cell nuclear antigen (PCNA) expression was also increased in CLL-treated HBx transgenic mice, indicating regeneration of damaged liver tissue. CLL treatment decreased expression of HBx and increased p21 and cyclin D1 in livers of HBx transgenic mice. In addition, p-p53 was increased after CLL treatment. These results suggest that CLL can have beneficial effects on the early and late stages of liver pathogenesis, preventing and delaying liver carcinogenesis. This drug should be considered as a potential chemopreventive agent for HBV-related hepatocarcinogenesis.

  14. Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity?

    Science.gov (United States)

    Cooke, Darren; Steward, William P; Gescher, Andreas J; Marczylo, Tim

    2005-09-01

    Consumption of fruits and berries has been associated with decreased risk of developing cancer. The most abundant flavonoid constituents of fruits and berries are anthocyans (i.e. anthocyanins, glycosides, and their aglycons, anthocyanidins) that cause intense colouration. In this review, we describe epidemiological evidence hinting at the cancer preventive activity of anthocyan-containing foods in humans, results of chemoprevention studies in rodent models with anthocyans or anthocyan-containing fruit/vegetable extracts, and pharmacological properties of anthocyans. Anthocyanidins have been shown to inhibit malignant cell survival and confound many oncogenic signalling events in the 10(-6)-10(-4) M concentration range. Studies of the pharmacokinetics of anthocyanins after their consumption as single agents, anthocyanin mixtures or berry extracts suggest that anthocyanins reach levels of 10(-8)-10(-7) M in human blood. It is unclear whether such concentrations are sufficient to explain anticarcinogenic effects, and whether anthocyanins exert chemopreventive efficacy themselves, or if they need to undergo hydrolysis to their aglyconic counterparts. The currently available literature provides tantalising hints of the potential usefulness of anthocyans or anthocyan mixtures as cancer chemopreventive interventions. Nevertheless further studies are necessary to help adjudge the propitiousness of their clinical development.

  15. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2013-01-01

    Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

  16. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  17. Chemoprevention of lung cancer by tea.

    Science.gov (United States)

    Clark, Julie; You, Ming

    2006-02-01

    Tea is the second only to water as the most consumed beverage in the world. Both green and black teas have been studied for their health benefits for a variety of diseases, particularly cancer. Lung cancer is the predominant cause of cancer mortality in developed countries. Smokers' risk of lung cancer is 20 times that of persons who have never smoked. Epidemiological studies on the cancer-preventive effects of tea produce inconsistent results, which could in part be attributed to the lack of a universal standard for tea preparations. However, most animal studies indicate that tea has strong chemopreventive effects against lung tumorigenesis. The reported mechanisms for chemopreventive activity of green tea are antioxidation, induction of phase II enzymes, inhibition of TNFalpha expression and release, inhibition of cell proliferation, and induction of apoptosis. Cell cycle arrest and apoptosis induced by green tea are probably the two most significant factors. Future studies are needed to determine how green tea affects the genes associated with cell cycle regulation and apoptosis during the mouse lung carcinogenesis process.

  18. BEI Resource Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — BEI Resources provides reagents, tools and information for studying Category A, B, and C priority pathogens, emerging infectious disease agents, non-pathogenic...

  19. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.

    Science.gov (United States)

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  20. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Madhulika Singh

    2014-01-01

    Full Text Available Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  1. Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Joydeb Kumar [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon [National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742 (Korea, Republic of)]. E-mail: surh@plaza.snu.ac.kr

    2005-12-11

    Center to the cancer biology is disrupted intracellular signaling network, which transmits improper signals resulting in abnormal cellular functioning. Therefore, modulation of inappropriate cell signaling cascades might be a rational approach in achieving chemoprevention. Inflammation has long been suspected to contribute to carcinogenesis. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer. Components of the cell signaling network, especially those converge on redox-sensitive transcription factor nuclear factor-{kappa}B involved in mediating inflammatory response, have been implicated in carcinogenesis. Intracellular signaling through another redox-sensitive transcription factor AP-1 and that transmitted via a more recently identified oncoprotein {beta}-catenin are also considered to be crucial for inflammation-associated cancer. Epidemiological and experimental studies have revealed that a wide variety of phytochemicals present in our daily diet are potential chemopreventive agents that can alter or correct undesired cellular functions caused by abnormal pro-inflammatory signal transmission. Modulation of cellular signaling involved in chronic inflammatory response by anti-inflammatory phytochemicals may comprise a rational and pragmatic strategy in molecular target-based chemoprevention.

  2. Privacy Impact Assessment (PIA) Repository

    Data.gov (United States)

    Department of Veterans Affairs — This repository contains Privacy Impact Assessments (PIA) that have been vetted/approved. Section 208 of the Electronic Government Act of 2002 (E-Gov Act) requires...

  3. Book Review: The Institutional Repository

    Directory of Open Access Journals (Sweden)

    Isabel Galina

    2007-03-01

    Full Text Available At a time when the future nature of scholarly communication and publishing are being debated this book serves as a useful reference guide for one of the key aspects- the institutional repository. Institutional repositories are a popular recent development for distributing and communicating research. They are a useful academic tool for administrating and publishing electronic resources produced by university members in order to increase access to these, both at an institutional and global level. However, there is still no general concensus about the characteristics of an institutional repository. What types of material are deposited? Who is responsible for building and maintaing a repository, how will copyright be managed, who will cover installation and maintenance costs? How will quality, integrity and preservation of the materials be assured?

  4. NIH Common Data Elements Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIH Common Data Elements (CDE) Repository has been designed to provide access to structured human and machine-readable definitions of data elements that have...

  5. Management of Indian Institutional Repositories

    OpenAIRE

    2010-01-01

    The study investigates various issues concerning the management of institutional repositories (IRs) developed in India. Data collection done using a web based questionnaire, created using software provided by surveymonkey.com. The entire population i.e. all IRs identified in India were surveyed. It was observed that in 42.86% (6) of Institutional Repositories implementation programmes were headed by librarians. No special staff was appointed by any institution for carrying out different jobs...

  6. Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

    OpenAIRE

    2013-01-01

    ABSTRACTBackground: Patients with chronic hepatitis B virus (HBV) infection are at a high risk to develop hepatocellular carcinoma (HCC). Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects ...

  7. An effective and simple procedure to isolate abundant quantities of biologically active chemopreventive lunasin-protease inhibitor concentrate (LPIC) from soybean

    Science.gov (United States)

    Lunasin is a 5-kDa soybean bioactive peptide with demonstrated anti-cancer and anti-inflammatory properties. The use of lunasin as a chemopreventive agent in large-scale animal studies and human clinical trials is hampered by the paucity of large quantities of lunasin. Recently, purification methods...

  8. Review article : the potential of combinational regimen with non-steroidal anti-inflammatory drugs in the chemoprevention of colorectal cancer

    NARCIS (Netherlands)

    Jalving, M; Koornstra, JJ; De Jong, S; De Vries, EGE; Kleibeuker, JH

    2005-01-01

    Non-steroidal anti-inflammatory drugs are chemopreventive agents in colorectal cancer. Non-steroidal anti-inflammatory drugs do not, however, offer complete protection against adenoma and carcinoma development. There is increasing interest in combining non-steroidal anti-inflammatory drugs with agen

  9. Demystifying the institutional repository for success

    CERN Document Server

    Buehler, Marianne

    2013-01-01

    Institutional repositories remain key to data storage on campus, fulfilling the academic needs of various stakeholders. Demystifying the Institutional Repository for Success is a practical guide to creating and sustaining an institutional repository through marketing, partnering, and understanding the academic needs of all stakeholders on campus. This title is divided into seven chapters, covering: traditional scholarly communication and open access publishing; the academic shift towards open access; what the successful institutional repository looks like; institutional repository collaboratio

  10. PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Hirokazu Takahashi

    2010-01-01

    Full Text Available Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARγ, such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARγ ligands could inhibit colorectal cancer cell growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF have come to be established as a biomarker of the risk of CRC in azoxymethane-treated mice and rats. In humans, ACF can be detected using magnifying colonoscopy. Previously, CRC and adenoma were used as a target for chemopreventive agents, but it needs a long time to evaluate, however, ACF can be a surrogate marker of CRC even for a brief period. In this clinical study, we investigated the chemopreventive effect of pioglitazone on the development of human ACF as a surrogate marker of CRC. Twenty-nine patients were divided into two groups, 20 were in the endoscopically normal control group and 9 were in the pioglitazone (15 mg/day group, and ACF and adenoma were examined before and after 1-month treatment. The number of ACF was significantly decreased (5.8±1.1 to 3.3±2.3 after 1 month of pioglitazone treatment, however, there was no significant change in the number of crypts/ACF or in the number and size of adenomas. Pioglitazone may have a clinical application as a cancer-preventive drug. This investigation is just a pilot study, therefore, further clinical studies are needed to show that the PPARγ ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis.

  11. The Fermilab Lattice Information Repository

    CERN Document Server

    Ostiguy, Jean-Francois; McCusker-Whiting, Michele; Michelotti, Leo

    2005-01-01

    Fermilab is a large accelerator complex with six rings and sixteen transfer beamlines operating in various modes and configurations, subject to modifications, improvements and occasional major redesign. Over the years, it became increasingly obvious that a centralized lattice repository with the ability to track revisions would be of great value. To that end, we evaluated potentially suitable revision systems, either freely available or commercial, and decided that expecting infrequent users to become fully conversant with complex revision system software was neither realistic nor practical. In this paper, we discuss technical aspects of the recently introduced FNAL Accelerator Division's Lattice Repository, whose fully web-based interface hides the complexity of Subversion, a comprehensive open source revision system. In particular we emphasize how the architecture of Subversion was a key ingredient in the technical success of the repository's implementation.

  12. Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo.

    Science.gov (United States)

    Iranshahi, M; Sahebkar, A; Hosseini, S T; Takasaki, M; Konoshima, T; Tokuda, H

    2010-03-01

    A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula diversivittata were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All of the tested compounds were active against EBV-EA activation. Among these compounds diversin (IC(50): 7.7) exhibited the strongest inhibitory effect and was selected to examine its effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited papilloma formation up to week 7 and the percentage of papilloma bearers was approximately 93.3% at week 20. The average number of papillomas formed per mouse was only 5.5 even at week 20. The results of the present investigation indicated that diversin might be valuable as a potent cancer chemopreventive agent and its potency was comparable with those of curcumin and quercetin, two well-known cancer chemopreventive agents.

  13. Population pharmacokinetic model for cancer chemoprevention with sulindac in healthy subjects.

    Science.gov (United States)

    Berg, Alexander K; Mandrekar, Sumithra J; Ziegler, Katie L Allen; Carlson, Elsa C; Szabo, Eva; Ames, Mathew M; Boring, Daniel; Limburg, Paul J; Reid, Joel M

    2013-04-01

    Sulindac is a prescription-based non-steroidal anti-inflammatory drug (NSAID) that continues to be actively investigated as a candidate cancer chemoprevention agent. To further current understanding of sulindac bioavailability, metabolism, and disposition, we developed a population pharmacokinetic model for the parent compound and its active metabolites, sulindac sulfide, and exisulind. This analysis was based on data from 24 healthy subjects who participated in a bioequivalence study comparing two formulations of sulindac. The complex disposition of sulindac and its metabolites was described by a seven-compartment model featuring enterohepatic recirculation and is the first reported population pharmacokinetic model for sulindac. The derived model was used to explore effects of clinical variables on sulindac pharmacokinetics and revealed that body weight, creatinine clearance, and gender were significantly correlated with pharmacokinetic parameters. Moreover, the model quantifies the relative bioavailability of the sulindac formulations and illustrates the utility of population pharmacokinetics in bioequivalence assessment. This novel population pharmacokinetic model provides new insights regarding the factors that may affect the pharmacokinetics of sulindac and the exisulind and sulindac sulfide metabolites in generally healthy subjects, which have implications for future chemoprevention trial design for this widely available agent.

  14. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  15. Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    A. Vieira

    2011-06-01

    Full Text Available β-ionone (βI, a cyclic isoprenoid, and geraniol (GO, an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight, GO (25 mg/100 g body weight, βI combined with GO or corn oil (control. Number of total aberrant crypt foci (ACF and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively compared to control (102 ± 9 and 17 ± 3 and without differences in the βI (91 ± 11 and 14 ± 3 and βI+GO groups (96 ± 5 and 19 ± 2. Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm² compared to control (0.91 ± 0.07 apoptotic cells/mm². The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

  16. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats.

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh

    2014-10-01

    Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight and reversed intratumor histopathological alterations. TPE dose-dependently suppressed proliferating cell nuclear antigen and cyclin D1 expression, induced apoptosis, upregulated proapoptotic protein Bax, downregulated antiapoptotic protein Bcl-2 and diminished the expression of nuclear and cytosolic β-catenin in mammary tumors. Our results clearly provide the first experimental evidence that TPE exerts chemopreventive effect in the classical DMBA model of breast cancer by suppressing abnormal cell proliferation and inducing apoptosis mediated through alteration of Bax/Bcl-2 ratio. Mechanistically, TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during an early-stage breast cancer. These results may encourage further

  17. Ascorbic acid in cancer chemoprevention: translational perspectives and efficacy.

    Science.gov (United States)

    Ullah, Mohammad F; Bhat, Showket H; Hussain, Eram; Abu-Duhier, Faisel; Ahmad, Aamir; Hadi, S M

    2012-12-01

    Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis has since decades attracted a considerable interest in plant-derived chemical constituents often termed as "phytochemicals" or sometimes as "Nutraceuticals" in case they are derived from dietary sources. A comprehensive search of the literature show that such an interest in natural product pharmacology has surged in the last 25 years and particularly risen at exponential rates since the last one decade. Phytochemicals such as curcumin (from spice turmeric), resveratrol (from red wine) and genistein (from soy) share the major efforts as indicated by overwhelming publications, despite skepticism concerning their bioavailability. Ascorbic acid (AA), the popular anti-oxidant in fruits and vegetables, has even a longer historical perspective than these dietary agents as for more than 35 years; there had been lingering questions about the efficacy of AA in cancer therapy. The footprints of AA from "scurvy" to "cancer" though complex seems to carry potential provided the puzzle could be set right. The use of AA in cancer treatment has been debated extensively as evident from the literature but surprisingly the complementing early phase bench work on the mechanistic studies for anticancer action was rather retarded. Proposed mechanisms of action for AA in the prevention and treatment of cancer includes antioxidant as well as pro-oxidant properties, stimulation of the immune system, altering carcinogen metabolism, enhancement of collagen synthesis necessary for tumor encapsulation and interference with cancer cell signaling. The observation that the intravenous administration of AA enhances its bioavailability to the extent of deriving pharmacological benefits against cancer has in recent years partially supported the clinical plausibility (efficacy) of AA towards realizing its translational advantage. Here, we provide an overview of AA with

  18. Repository operational criteria comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hageman, J.P.; Chowdhury, A.H. [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses

    1994-06-01

    The objective of the ``Repository Operational Criteria (ROC) Feasibility Studies`` (or ROC task) was to conduct comprehensive and integrated analyses of repository design, construction, and operations criteria in 10 CFR Part 60 regulations considering the interfaces among the components of the regulations and impacts of any potential changes to those regulations. The ROC task addresses regulatory criteria and uncertainties related to the preclosure aspects of the geologic repository. Those parts of 10 CFR Part 60 that require routine guidance or minor changes to the rule were addressed in Hageman and Chowdhury, 1992. The ROC task shows a possible need for further regulatory clarity, by major changes to the rule, related to the design bases and siting of a geologic repository operations area and radiological emergency planning in order to assure defense-in-depth. The analyses, presented in this report, resulted in the development and refinement of regulatory concepts and their supporting rationale for recommendations for potential major changes to 10 CFR Pan 0 regulations.

  19. The MEANING multilingual central repository

    NARCIS (Netherlands)

    Atserias, J.; Villarejo, L.; Rigau, G.; Agirre, E.; Carroll, J.; Magnini, B.; Vossen, P.

    2004-01-01

    This paper describes the first version of the Multilingual Central Repository, a lexical knowledge base developed in the framework of the MEANING project. Currently the MCR integrates into the EuroWordNet framework five local wordnets (including four versions of the English WordNet from Princeton),

  20. In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium.

    Science.gov (United States)

    Gamal-Eldeen, Amira M; Ahmed, Eman F; Abo-Zeid, Mona A

    2009-06-01

    Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 microg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-alpha (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia.

  1. Faulty assumptions for repository requirements

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, W G

    1999-06-03

    Long term performance requirements for a geologic repository for spent nuclear fuel and high-level waste are based on assumptions concerning water use and subsequent deaths from cancer due to ingesting water contaminated with radio isotopes ten thousand years in the future. This paper argues that the assumptions underlying these requirements are faulty for a number of reasons. First, in light of the inevitable technological progress, including efficient desalination of water, over the next ten thousand years, it is inconceivable that a future society would drill for water near a repository. Second, even today we would not use water without testing its purity. Third, today many types of cancer are curable, and with the rapid progress in medical technology in general, and the prevention and treatment of cancer in particular, it is improbable that cancer caused by ingesting contaminated water will be a sign&ant killer in the far future. This paper reviews the performance requirements for geological repositories and comments on the difficulties in proving compliance in the face of inherent uncertainties. The already tiny long-term risk posed by a geologic repository is presented and contrasted with contemporary every day risks. A number of examples of technological progress, including cancer treatments, are advanced. The real and significant costs resulting from the overly conservative requirements are then assessed. Examples are given of how money (and political capital) could be put to much better use to save lives today and in the future. It is concluded that although a repository represents essentially no long-term risk, monitored retrievable dry storage (above or below ground) is the current best alternative for spent fuel and high-level nuclear waste.

  2. A Comparative Analysis of Institutional Repository Software

    OpenAIRE

    2010-01-01

    This proposal outlines the design of a comparative analysis of the four institutional repository software packages that were represented at the 4th International Conference on Open Repositories held in 2009 in Atlanta, Georgia: EPrints, DSpace, Fedora and Zentity (The 4th International Conference on Open Repositories website, https://or09.library.gatech.edu). The study includes 23 qualitative and quantitative measures taken from default installations of the four repositories on a benchmark ma...

  3. Digital Preservation Initiatives in Ontario: Trusted Digital Repositories and Research Data Repositories

    Directory of Open Access Journals (Sweden)

    Wayne Johnston

    2012-12-01

    Full Text Available The first in a series of two articles dealing with digital preservation, this article discusses repositories, more specifically Trusted Digital Repositories (TDR and Research Data Repositories. The focus will be on the TDRs at Scholars Portal and Library and Archives Canada (LAC, and the data repository at the University of Guelph.

  4. Resveratrol enhances the chemopreventive effect of celecoxib in chemically induced breast cancer in rats.

    Science.gov (United States)

    Kisková, Terézia; Jendželovský, Rastislav; Rentsen, Erdenetsetsek; Maier-Salamon, Alexandra; Kokošová, Natália; Papčová, Zuzana; Mikeš, Jaromír; Orendáš, Peter; Bojková, Bianka; Kubatka, Peter; Svoboda, Martin; Kajo, Karol; Fedoročko, Peter; Jäger, Walter; Ekmekcioglu, Cem; Kassayová, Monika; Thalhammer, Theresia

    2014-11-01

    Resveratrol and celecoxib were used as chemopreventive agents in animal models of carcinogenesis, and exert antiproliferative and proapoptotic effects on cancer cells. Therefore, the aim of this study was to evaluate whether combining resveratrol with celecoxib may exert more potent anticarcinogenic effects than the single agents. Mammary carcinogenesis was initiated in 70 female Sprague-Dawley rats with N-methyl-N-nitrosourea (NMU). The chemoprevention with resveratrol, celecoxib, and their combination started 2 weeks before the first carcinogen dose and lasted until the end of the experiment. Tumor incidence and frequency, latency period, tumor volume, the expression of cyclooxygenase 2 (COX2) and growth differentiation factor 15 (GDF15), and also the formation of reactive oxygen species were analyzed using different methods. In addition, the levels of resveratrol and its metabolites in blood and selected tumor tissues were determined by high-performance liquid chromatography. Finally, the anticancer effects of the reagents were studied in the human breast cancer cell line MCF-7. Celecoxib as a single agent significantly decreased tumor frequency, prolonged tumor latency, and decreased the total number of malignant tumors compared with the NMU conditions. Tumor volume was nonsignificantly reduced (0.68±0.25 vs. 0.93±0.28 cm3). Importantly, the addition of resveratrol to celecoxib reduced tumor volume by 60% compared with celecoxib alone (from 0.68±0.25 to 0.27±0.07 cm3, Pcancer-preventive effects of this application. This study showed that in NMU-induced mammary cancer in rats, the combination of resveratrol and celecoxib led to a significant reduction in all tumor parameters. In addition, in terms of tumor volume, the combination was more efficient than celecoxib as a single agent.

  5. Consistency Analysis of Network Traffic Repositories

    NARCIS (Netherlands)

    Lastdrager, Elmer; Pras, Aiko

    2009-01-01

    Traffic repositories with TCP/IP header information are very important for network analysis. Researchers often assume that such repositories reliably represent all traffic that has been flowing over the network; little thoughts are made regarding the consistency of these repositories. Still, for var

  6. Consistency of Network Traffic Repositories: An Overview

    NARCIS (Netherlands)

    Lastdrager, E.; Pras, A.

    2009-01-01

    Traffc repositories with TCP/IP header information are very important for network analysis. Researchers often assume that such repositories reliably represent all traffc that has been flowing over the network; little thoughts are made regarding the consistency of these repositories. Still, for vario

  7. Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors.

    Science.gov (United States)

    Witschi, H

    2000-12-01

    Strain A/J mice underwent whole body exposure for 6 hours a day, 5 days a week, for 5 months to a mixture of cigarette sidestream and mainstream smoke (89%-11%; total suspended particulates 80-150 mg/m3), then were kept for another 4 months in air before being killed for scoring of lung tumors. In 7 independent experiments, lung tumor multiplicity was significantly increased in all 7 trials and lung tumor incidence in 5. When animals were kept for 9 months in smoke, lung tumor multiplicity was not significantly higher than in controls, although lung tumor incidence was. The following chemopreventive agents were evaluated: green tea, phenethyl isothiocyanate (PEITC), acetylsalicylic acid (ASA), N-acetylcysteine (NAC), p-XSC (1,4-phenylenebis[methylene]selenocyanate), d-limonene (DL), and a mixture of PEITC and BITC (benzyl isothiocyanate). In animals exposed to tobacco smoke, none of these agents reduced lung tumor multiplicity or incidence. As a control, the effects of the same agents were examined in A/J mice initiated with 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) or urethane. In mice injected with NNK, green tea and ASA did not reduce lung tumor multiplicities and NAC had no effect on urethane-induced lung tumors, whereas PEITC, p-XSC and DL reduced NNK-induced tumor multiplicities to 20% to 50% of control values. On the other hand, dietary mixture of myoinositol and dexamethasone was not only highly protective against NNK, but reduced lung tumor multiplicities and incidence in smoke-exposed animals to control values. This effect was also seen when the animals were fed the myo-inositol-dexamethasone mixture once they were removed from smoke. It is concluded that in animal studies it might be preferable to evaluate the effectiveness of putative chemopreventive agents against full tobacco smoke rather than against selected model compounds. The observations made with myo-inositol-dexamethasone suggest that people who have recently quit smoking might

  8. Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

    Directory of Open Access Journals (Sweden)

    De-Xing Hou

    2004-01-01

    Full Text Available Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK pathway and activator protein 1 (AP-1 factor; (ii suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB pathway and cyclooxygenase 2 (COX-2 gene; (iii apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS / c-Jun NH2-terminal kinase (JNK-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention.

  9. Experimental DML over digital repositories in Japan

    CERN Document Server

    Namiki, Takao; Naruse, Shunsuke

    2009-01-01

    In this paper the authors show an overview of Virtual Digital Mathematics Library in Japan (DML-JP), contents of which consist of metadata harvested from institutional repositories in Japan and digital repositories in the world. DML-JP is, in a sense, a subject specific repository which collaborate with various digital repositories. Beyond portal website, DML-JP provides subject-specific metadata through OAI-ORE. By the schema it is enabled that digital repositories can load the rich metadata which were added by mathematicians.

  10. Online educational repositories for promoting agricultural knowledge

    Directory of Open Access Journals (Sweden)

    C.I. Costopoulou

    2010-11-01

    Full Text Available Towards promoting sustainable agriculture and economic growth, the development of the agricultural workforce and set up of innovative agricultural systems are required. Agricultural educational repositories are systems used for storing, reusing and sharing agricultural learning resources. They contribute to agricultural education at different educational levels and target groups. Thus, this paper firstly provides an overview of Institutional repositories (IRs and Open Access Archives (OAAs in Greece and agricultural repositories worldwide. Also, it describes the agricultural repositories that provide access to educational content in Greek and presents experiences from the establishment of Agricultural University of Athens’ (AUA repository.

  11. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  12. Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice.

    Science.gov (United States)

    Hamizah, Sulaiman; Roslida, A H; Fezah, O; Tan, K L; Tor, Y S; Tan, C I

    2012-01-01

    Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(α)anthracene (DMBA 100 μg/100 μl acetone) and promotion by repeated application of croton oil (1% in acetone/ twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300 mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (pmuricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

  13. Nutrient and nonnutrient components of legumes, and its chemopreventive activity: a review.

    Science.gov (United States)

    Sánchez-Chino, Xariss; Jiménez-Martínez, Cristian; Dávila-Ortiz, Gloria; Álvarez-González, Isela; Madrigal-Bujaidar, Eduardo

    2015-01-01

    Legumes in combination with other products are the staple food for a large part of the world population, especially the low-income fragment, because their seeds provide valuable amounts of carbohydrates, fiber, and proteins, and have an important composition of essential amino acids, the sulphured amino acids being the limiting ones. Furthermore, legumes also have nonnutritional compounds that may decrease the absorption of nutrients or produce toxic effects; however, it has been reported that depending on the dose, these nonnutritional compounds also have different bioactivities as antioxidant, hypolipidemic, hypoglycemic, and anticarcinogenic agents, which have been proven in scientific studies. It has been observed that in countries with a high consumption of legumes, the incidence of colorectal cancer is lower. Some studies have shown that legume seeds are an alternative chemopreventive therapy against various cancers especially colon; this was verified in various animal models of induced by azoxymethane, a colon specific carcinogenic compound, in which a diet was supplemented with different concentrations of beans, lentils, chickpeas, or soybeans, mostly. These studies have proven the anticancer activity of legumes in early stages of carcinogenesis. Therefore, it is important to review the information available to elucidate the chemopreventive mechanisms of action of legume compounds.

  14. The chemopreventive bioflavonoid apigenin modulates signal transduction pathways in keratinocyte and colon carcinoma cell lines.

    Science.gov (United States)

    Van Dross, Rukiyah; Xue, Yue; Knudson, Alexandra; Pelling, Jill C

    2003-11-01

    Apigenin is a nonmutagenic chemopreventive agent found in fruits and green vegetables. In this study, we used two different epithelial cell lines (308 mouse keratinocytes and HCT116 colon carcinoma cells) to determine the effect of apigenin on the mitogen-activated protein kinase (MAPK) cascade. Apigenin induced a dose-dependent phosphorylation of both extracellular signal-regulated protein kinase (ERK) and p38 kinase but had little effect on the phosphorylation of c-jun amino terminal kinase (JNK). We used immunoprecipitation-coupled kinase assays to show that apigenin increased the kinase activity of ERK and p38 but not JNK. Consistent with these results, we found that apigenin induced a 7.4-fold induction in the phosphorylation of Elk, the downstream phosphorylation target of ERK kinase. Similarly, apigenin induced a 3.2-fold induction in the phosphorylation of activating transcription factor-2, the downstream phosphorylation target of p38 kinase. Little change was observed in the phosphorylation of c-jun, the phosphorylation target of JNK. These data suggest that part of the chemopreventive activity of apigenin may be mediated by its ability to modulate the MAPK cascade.

  15. Benzo(a)pyrene induced lung cancer: Role of dietary phytochemicals in chemoprevention.

    Science.gov (United States)

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Sriram, Chandra Shekhar; Gogoi, Ranadeep

    2015-10-01

    Lung cancer is the major cause of overall cancer deaths, and chemoprevention is a promising strategy to control this disease. Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is one among the principal constituents of tobacco smoke that plays a key role in lung carcinogenesis. The B(a)P induced lung cancer in mice offers a relevant model to study the effect of natural products and has been widely used by many researchers and found considerable success in ameliorating the pathophysiological changes of lung cancer. Currently available synthetic drugs that constitute the pharmacological armamentarium are themselves effective in managing the condition but not without setbacks. These hunches have accelerated the requisite for natural products, which may be used as dietary supplement to prevent the progress of lung cancer. Besides, these agents also supplement the conventional treatment and offer better management of the condition with less side effects. In the context of soaring interest toward dietary phytochemicals as newer pharmacological interventions for lung cancer, in the present review, we are attempting to give a silhouette of mechanisms of B(a)P induced lung carcinogenesis and the role of dietary phytochemicals in chemoprevention.

  16. Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

    Science.gov (United States)

    Budán, Ferenc; Szabó, István; Varjas, Tímea; Nowrasteh, Ghodratollah; Dávid, Tamás; Gergely, Péter; Varga, Zsuzsa; Molnár, Kornélia; Kádár, Balázs; Orsós, Zsuzsa; Kiss, István; Ember, István

    2011-04-01

    A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

  17. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  18. Digital Repository of Mathematical Formulae

    OpenAIRE

    Howard S. Cohl; McClain, Marjorie A.; Saunders, Bonita V.; Schubotz, Moritz; Williams, Janelle C.

    2014-01-01

    The purpose of the NIST Digital Repository of Mathematical Formulae (DRMF) is to create a digital compendium of mathematical formulae for orthogonal polynomials and special functions (OPSF) and of associated mathematical data. The DRMF addresses needs of working mathematicians, physicists and engineers: providing a platform for publication and interaction with OPSF formulae on the web. Using MediaWiki extensions and other existing technology (such as software and macro collections developed f...

  19. Repository development status in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Beceiro, Alvaro; Zuloaga, Pablo [ENRESA (Spain)

    2009-06-15

    The paper describes the status of repository development for the different waste categories. Low and Intermediate Waste Disposal facility of El Cabril was commissioned in 1992 and is in normal operation. The major modifications and activities during the last years are the adaptation to waste streams not initially foreseen such as some decommissioning waste or waste from steel industry, and the improvement of its performance assessment, supported by a R and D and refined models. As part of this facility, a new disposal facility specifically intended for very low activity waste has been constructed and commissioned in July 2008. Its design is based on the European Directive for hazardous waste disposal. National policy for Nuclear Spent Fuel and High-Level waste is focused on the development of a centralized storage facility of the vault type, whose site location would be selected through a volunteering process. Meanwhile, with the aim of solving specific problems, three individual storage facilities are in different status at reactor sites. Research on final solution, including some repository aspects as well as separation and transmutation are being carried out in accordance to ENRESA's R and D program. ENRESA has developed conceptual designs for non site specific repositories, both in granite and clay, and has carried out their corresponding performance assessment exercises. (authors)

  20. Identifying Molecular Targets for Chemoprevention in a Rat Model

    Science.gov (United States)

    2007-06-01

    were incubated in 10mMcitrate at 100jC. Primary antibodies were incubated overnight at room temperature in phosphate- buffered saline. We used the...Murakoshi M, Nishino H, and Shirai T (2001). Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carci- nogenesis

  1. A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes.

    Science.gov (United States)

    Dickinson, Sally E; Olson, Erik R; Levenson, Corey; Janda, Jaroslav; Rusche, Jadrian J; Alberts, David S; Bowden, G Timothy

    2014-09-15

    One of the primary components of the East Indian sandalwood oil (EISO) is α-santalol, a molecule that has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been extensively investigated even though it is widely used in cultures around the world for its health benefits as well as for its fragrance and as a cosmetic. In the current study, we show for the first time that EISO-treatment of HaCaT keratinocytes results in a blockade of cell cycle progression as well as a concentration-dependent inhibition of UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, these effects were not mediated through an inhibition of signaling upstream of AP-1, as EISO treatment did not inhibit UV-induced Akt or MAPK activity. Low concentrations of EISO were found to induce HaCaT cell death, although not through apoptosis as annexin V and PARP cleavage were not found to increase with EISO treatment. However, plasma membrane integrity was severely compromised in EISO-treated cells, which may have led to cleavage of LC3 and the induction of autophagy. These effects were more pronounced in cells stimulated to proliferate with bovine pituitary extract and EGF prior to receiving EISO. Together, these effects suggest that EISO may exert beneficial effects upon skin, reducing the likelihood of promotion of pre-cancerous cells to actinic keratosis (AK) and skin cancer.

  2. Fresh garlic extract inhibits Staphylococcus aureus biofilm formation under chemopreventive and chemotherapeutic conditions

    Directory of Open Access Journals (Sweden)

    Panan Ratthawongjirakul

    2016-08-01

    Full Text Available Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA are the leading aetiological pathogens of nosocomial infections worldwide. These bacteria form biofilms on both biotic and abiotic surfaces causing biofilm-associated infections. Within the biofilm, these bacteria might develop persistent and antimicrobial resistant characteristics resulting in chronic infections and treatment failures. Garlic exhibits broad pharmaceutical properties and inhibitory activities against S. aureus. We investigated the effects of aqueous fresh garlic extract on biofilm formation in S. aureus ATCC25923 and MRSA strains under chemopreventive and chemotherapeutic conditions. The viable bacteria and biofilm levels were quantified through colony count and crystal violet staining, respectively. The use of fresh garlic extract under both conditions significantly inhibited biofilm formation in S. aureus strains ATCC25923 and MRSA. Garlic could be developed as either a prophylactic or therapeutic agent to manage S. aureus biofilm-associated infections.

  3. Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

    OpenAIRE

    Pietrofesa, Ralph A; Anastasia Velalopoulou; Albelda, Steven M.; Melpo Christofidou-Solomidou

    2016-01-01

    The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as a...

  4. Author Identifiers in Scholarly Repositories

    CERN Document Server

    Warner, Simeon

    2010-01-01

    Bibliometric and usage-based analyses and tools highlight the value of information about scholarship contained within the network of authors, articles and usage data. Less progress has been made on populating and using the author side of this network than the article side, in part because of the difficulty of unambiguously identifying authors. I briefly review a sample of author identifier schemes, and consider use in scholarly repositories. I then describe preliminary work at arXiv to implement public author identifiers, services based on them, and plans to make this information useful beyond the boundaries of arXiv.

  5. Building didactic content repositories: method and tools

    OpenAIRE

    Jacek Marciniak

    2012-01-01

    The article presents the method and tools which allows to build repositories of didactic materials in SCORM using UCTS taxonomic system and Content Repository software. SCORM is a universal specification designed to create reusable materials in digital format. UCTS is a taxonomic model which allows to attribute didactic interpretations to content components. Content Repository is a web software designed to create, store and process didactic content in SCORM. The method was verified while crea...

  6. The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target.

    Science.gov (United States)

    Fishel, Melissa L; Kelley, Mark R

    2007-01-01

    With our growing understanding of the pathways involved in cell proliferation and signaling, targeted therapies, in the treatment of cancer are entering the clinical arena. New and emerging targets are proteins involved in DNA repair pathways. Inhibition of various proteins in the DNA repair pathways sensitizes cancer cells to DNA damaging agents such as chemotherapy and/or radiation. We study the apurinic endonuclease 1/redox factor-1 (Ape1/Ref-1) and believe that its crucial function in DNA repair and reduction-oxidation or redox signaling make it an excellent target for sensitizing tumor cells to chemotherapy. Ape1/Ref-1 is an essential enzyme in the base excision repair (BER) pathway which is responsible for the repair of DNA caused by oxidative and alkylation damage. As importantly, Ape1/Ref-1 also functions as a redox factor maintaining transcription factors in an active reduced state. Ape1/Ref-1 stimulates the DNA binding activity of numerous transcription factors that are involved in cancer promotion and progression such as AP-1 (Fos/Jun), NFkappaB, HIF-1alpha, CREB, p53 and others. We will discuss what is known regarding the pharmacological targeting of the DNA repair activity, as well as the redox activity of Ape1/Ref-1, and explore the budding clinical utility of inhibition of either of these functions in cancer treatment. A brief discussion of the effect of polymorphisms in its DNA sequence is included because of Ape1/Ref-1's importance to maintenance and integrity of the genome. Experimental modification of Ape1/Ref-1 activity changes the response of cells and of organisms to DNA damaging agents, suggesting that Ape1/Ref-1 may also be a productive target of chemoprevention. In this review, we will provide an overview of Ape1/Ref-1's activities and explore the potential of this protein as a target in cancer treatment as well as its role in chemoprevention.

  7. Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer.

    Science.gov (United States)

    Hadi, S M; Ullah, M F; Azmi, A S; Ahmad, A; Shamim, U; Zubair, H; Khan, H Y

    2010-06-01

    Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.

  8. The European Repository Landscape 2008 Inventory of Digital Repositories for Research Output

    CERN Document Server

    Van der Graaf, Maurits

    2009-01-01

    It is widely acknowledged that a common knowledge base for European research is necessary. Research repositories are an important innovation to the scientific information infrastructure. In 2006, digital repositories in the 27 countries of the European we

  9. Center for Leadership Development (CLD) Repository

    Data.gov (United States)

    Office of Personnel Management — The Center for Leadership Development Repository stores various data including policies, procedures, governance, guidance, security, and financial documents of the...

  10. Workshop: Creating Your Institutional Research Repository

    KAUST Repository

    Grenz, Daryl M.

    2016-11-08

    In 2002, the Scholarly Publishing and Academic Resources Coalition (SPARC) proposed the concept of an institutional repository to simultaneously disrupt and enhance the state of scholarly communications in the academic world. Thirteen years later, thousands of universities and other institutions have answered this call, but many more have not due to gaps in budgets, awareness and, most of all, practical guidance on creating an institutional repository. This workshop provides you with an essential primer on what it takes to establish a fully-functioning institutional repository. Every aspect of the process will be covered, including policies, procedures, staffing guidelines, workflows and repository technologies.

  11. E-Thesis Repositories: The Asian Scenario

    Directory of Open Access Journals (Sweden)

    Shantashree Sengupta

    2012-06-01

    Full Text Available Across the globe, people are trying to find out ways to make the findings of research freely available to the public through open access institutional repositories. Theses and dissertations are considered to be one of the most important sources of scholarly communication. Due to various benefits of electronic theses and dissertations over the print format, various institutions are developing their own e-thesis repositories. Various Asian countries have contributed to the development of e-thesis repositories. The present study gives an overview of the growth and development of e-thesis repositories in Asia with the data from the OpenDOAR database.

  12. Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers.

    Science.gov (United States)

    Schuller, Hildegard M; Porter, B; Riechert, A; Walker, K; Schmoyer, R

    2004-07-01

    Lung cancer continues to be the leading cause of cancer death in developed countries. With smoking the major etiological factor for lung cancer, there is a great need for the development of chemopreventive treatments that inhibit the progression of initiated cells and premalignant lesions into overt lung cancer in smokers who quit. Although the major focus of chemoprevention research has been on agents that inhibit the metabolic activation of genotoxic chemicals contained in tobacco products, some of these agents may additionally modulate growth-regulating signal transduction. In turn, the function of such signaling pathways is highly cell type-specific, with a given pathway inhibiting the growth of one cell type while stimulating the growth of others. The current experiment has tested the hypothesis that green tea and the methylxanthine theophylline contained in tea inhibit the progression of neuroendocrine lung carcinogenesis in hamsters with hyperoxic lung injury and initiated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while promoting the development of Clara cell-derived pulmonary adenocarcinomas initiated by NNK in healthy hamsters. This hypothesis is based on published evidence that human small cell lung cancer as well as the neuroendocrine hamster tumors are regulated via autocrine signaling pathways that activate Raf-1 and the mitogen-activated (MAP) kinase pathway whereas human pulmonary adenocarcinomas of Clara cell lineage and the hamster model of this cancer type are regulated by a beta-adrenergic pathway involving the activation of cyclic adenosine 3',5'-monophosphate (cAMP) and the arachidonic acid (AA) cascade. In turn, it was hypothesized that theophylline would inhibit Raf-1-dependent tumor progression while promoting cAMP-dependent tumor progression due to its documented ability to inhibit the enzyme cAMP-phophodiesterase. The experimental design simulated chemoprevention in former smokers in that treatments

  13. Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

    Directory of Open Access Journals (Sweden)

    Wen-Chuan Hsieh

    2013-09-01

    Full Text Available ABSTRACTBackground: Patients with chronic hepatitis B virus (HBV infection are at a high risk to develop hepatocellular carcinoma (HCC. Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects on activating peroxisome proliferator activated receptors (PPAR and inhibiting mTOR signaling in a transgenic mice model harboring HBV viral oncoproteins.Methods: The transgenic mice model harboring HBx and pre-S2 mutant constructs which develop HCC was adopted. First, we in vitro tested the ideal combination dosages of the silymarin and resveratrol product, and then we fed the natural product to the transgenic mice.The chemopreventive effects on preventing the development of HCC were evaluated.Results: MTT assay showed an enhanced effect of the combined silymarin and resveratrol product on the reduction of cell proliferation in two hepatoma cell lines, Huh-7 and Hep G2. In vitro reporter assay and Western blot analyses revealed that the combined product couldactivate PPAR/PGC-1 signaling and inhibit mTOR expression. In vivo, the combined products could significantly ameliorate fatty liver and reduce HCCs in transgenic miceharboring HBV oncoproteins.Conclusions: The combined silymarin and resveratrol product exhibits a synergistic effect on the reduction of HCC development in transgenic mice model and may represent a potential agent for the prevention of HCC in high risk chronic HBV carriers.Key words: HBV, HCC, Transgenic mice, Chemoprevention

  14. Asset Reuse of Images from a Repository

    Science.gov (United States)

    Herman, Deirdre

    2014-01-01

    According to Markus's theory of reuse, when digital repositories are deployed to collect and distribute organizational assets, they supposedly help ensure accountability, extend information exchange, and improve productivity. Such repositories require a large investment due to the continuing costs of hardware, software, user licenses, training,…

  15. Reference repository design concept for bedded salt

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.W.; Martin, R.W.

    1980-10-08

    A reference design concept is presented for the subsurface portions of a nuclear waste repository in bedded salt. General geologic, geotechnical, hydrologic and geochemical data as well as descriptions of the physical systems are provided for use on generic analyses of the pre- and post-sealing performance of repositories in this geologic medium. The geology of bedded salt deposits and the regional and repository horizon stratigraphy are discussed. Structural features of salt beds including discontinuities and dissolution features are presented and their effect on repository performance is discussed. Seismic hazards and the potential effects of earthquakes on underground repositories are presented. The effect on structural stability and worker safety during construction from hydrocarbon and inorganic gases is described. Geohydrologic considerations including regional hydrology, repository scale hydrology and several hydrological failure modes are presented in detail as well as the hydrological considerations that effect repository design. Operational phase performance is discussed with respect to operations, ventilation system, shaft conveyances, waste handling and retrieval systems and receival rates of nuclear waste. Performance analysis of the post sealing period of a nuclear repository is discussed, and parameters to be used in such an analysis are presented along with regulatory constraints. Some judgements are made regarding hydrologic failure scenarios. Finally, the design and licensing process, consistent with the current licensing procedure is described in a format that can be easily understood.

  16. Cutting edge: chemoprevention of colorectal neoplasia in inflammatory bowel disease.

    Science.gov (United States)

    Actis, Giovanni C; Tarallo, Sonia; Rosina, Floriano

    2013-02-01

    Colitis-associated cancer represents a long-standing problem, with two new factors adding to its importance: the diffusion of inflammatory bowel disease in developing countries, and the increased availability of effective drugs that control ulcerative colitis delaying or abrogating the need for a curative colectomy. The consolidated evidence that inflammation is the unique variable that factors in colitic cancer development has conferred impetus to the search and release of anti-inflammatory/immune suppressive molecules to pursue the goal of cancer chemoprevention. Cutting-edge research has provided breakthrough insights into the mechanism of the chemopreventive actions of mesalamines, thiopurines, and probiotics, and we expand on these topics. Despite these advancements, bedside evidence is still mixed and calls for further scrutiny. Nowadays, the clinician must continue to rely on classic preventive measures such as surveillance colonoscopy, and the early and aggressive use of drugs that permit to keep the degree of mucosal inflammation to a minimum.

  17. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sebastiano Cimino

    2012-01-01

    Full Text Available Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

  18. Shrimp Lipids: A Source of Cancer Chemopreventive Compounds

    Directory of Open Access Journals (Sweden)

    Armando Burgos-Hernández

    2013-10-01

    Full Text Available Shrimp is one of the most popular seafoods worldwide, and its lipids have been studied for biological activity in both, muscle and exoskeleton. Free fatty acids, triglycerides, carotenoids, and other lipids integrate this fraction, and some of these compounds have been reported with cancer chemopreventive activities. Carotenoids and polyunsaturated fatty acids have been extensively studied for chemopreventive properties, in both in vivo and in vitro studies. Their mechanisms of action depend on the lipid chemical structure and include antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory activities, among others. The purpose of this review is to lay groundwork for future research about the properties of the lipid fraction of shrimp.

  19. Building didactic content repositories: method and tools

    Directory of Open Access Journals (Sweden)

    Jacek Marciniak

    2012-12-01

    Full Text Available The article presents the method and tools which allows to build repositories of didactic materials in SCORM using UCTS taxonomic system and Content Repository software. SCORM is a universal specification designed to create reusable materials in digital format. UCTS is a taxonomic model which allows to attribute didactic interpretations to content components. Content Repository is a web software designed to create, store and process didactic content in SCORM. The method was verified while creating E-archeology Content Repository which stores e-learning materials on protection and management of archeological heritage. The repository contains approximately 4500 Learning Objects in 5 languages and about 800 components of didactically useful e-learning components described in UCTS.

  20. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  1. Anticarcinogenic Effects of Dietary Phytoestrogens and Their Chemopreventive Mechanisms.

    Science.gov (United States)

    Hwang, Kyung-A; Choi, Kyung-Chul

    2015-01-01

    Phytoestrogens are phenolic compounds derived from plants and exert an estrogenic as well as an antiestrogenic effect and also various biological efficacies. Chemopreventive properties of phytoestrogens has emerged from epidemiological observations indicating that the incidence of some cancers including breast and prostate cancers is much lower in Asian people, who consume significantly higher amounts of phytoestrogens than Western people. There are 4 main classes of phytoestrogens: isoflavones, stilbenes, coumestans, and lignans. Currently, resveratrol is recognized as another major phytoestrogen present in grape and red wine and has been studied in many biological studies. Phytoestrogens have biologically diverse profitabilities and advantages such as low cytotoxicity to patients, lack of side effects in clinical trials, and pronounced benefits in a combined therapy. In this review, we highlighted the effects of genistein, daidzein, and resveratrol in relation with their anticarcinogenic activity. A lot of in vitro and in vivo results on their chemopreventive properties were presented along with the underlying mechanisms. Besides well-known mechanisms such as antioxidant property and apoptosis, newly elucidated anticarcinogenic modes of action including epigenetic modifications and topoisomerase inhibition have been provided to examine the possibility of phytoestrogens as promising reagents for cancer chemoprevention and/or treatment and to suggest the importance of plant-based diet of phytoestrogens.

  2. Molecular aspects and chemoprevention of dimethylaminoazobenzene-induced hepatocarcinogenesis: A review.

    Science.gov (United States)

    Thomas, Nisha Susan; George, Kiran; Namasivayam, Nalini

    2016-01-01

    The lipophilic azo dye dimethylaminoazobenzene (DAB) is a potent hepatocarcinogen accounted as a group-2B carcinogen causing risk to humans. DAB is commonly used as a coloring agent in food, pharmaceuticals, beverages, soap and polishes. The exploration of DAB-induced hepatocarcinogenesis in animal models helped to an extent to perceive the histological, biochemical and molecular mechanisms of DAB carcinogenesis and also the severity of DAB exposure to humans. In experimental animal models, it is well-proved that the procarcinogen DAB is predominantly metabolized by cytochrome P450 enzymes giving rise to the formation of toxic electrophiles and reactive oxygen species (ROS), which further forms DNA adducts leading to the development of hepatic tumors. Recently, research evidence suggests that dietary phytochemicals and plant polyphenols are promising agents to control the incidence of DAB-induced hepatocarcinogenesis by preventing the generation of toxic electrophiles and ROS thereby inhibiting the formation of DNA adducts. This review highlights the role of specific dietary factors, biotransformation of DAB, phenotypic and genotypic alterations, and significance of certain chemopreventive agents against DAB-induced hepatocarcinogenesis.

  3. Australian clinicians and chemoprevention for women at high familial risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Keogh Louise A

    2009-05-01

    Full Text Available Abstract Objectives Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Methods Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Results Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers, practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it, and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments. Conclusion The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.

  4. Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin.

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R; Liu, Zhonglin; Barber, Christy; Petricoin, Emanuel F; Calvert, Valerie S; Einspahr, Janine; Dickinson, Jesse E; Stratton, Steven P; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M; Dong, Zigang; Alberts, David S; Timothy Bowden, G

    2016-03-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here, we explored the use of topical rapamycin as a chemopreventive agent in the context of solar-simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared with controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared with vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  5. Inhibition of akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  6. Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention.

    Science.gov (United States)

    Chun, Kyung-Soo; Surh, Young-Joon

    2004-09-15

    Expression of cyclooxygenase-2 (COX-2) has been reported to be elevated in human colorectal adenocarcinoma and other tumors, including those of breast, cervical, prostate, and lung. Genetic knock-out or pharmacological inhibition of COX-2 has been shown to protect against experimentally-induced carcinogenesis. Results from epidemiological and laboratory studies indicate that regular intake of selective COX-2 inhibitors reduces the risk of several forms of human malignancies. Thus, it is conceivable that targeted inhibition of abnormally or improperly elevated COX-2 provides one of the most effective and promising strategies for cancer chemoprevention. The COX-2 promoter contains a TATA box and binding sites for several transcription factors including nuclear factor-kappaB (NF-kappaB), nuclear factor for interleukin-6/CCAAT enhancer-binding protein (NF-IL6/C/EBP) and cyclic AMP response element (CRE) binding protein. Upregulation of COX-2 is mediated by a variety of stimuli including tumor promoters, oncogenes, and growth factors. Stimulation of either protein kinase C (PKC) or Ras signaling enhances mitogen-activated protein kinase (MAPK) activity, which, in turn, activates transcription of cox-2. Celecoxib, the first US FDA approved selective COX-2 inhibitor, initially developed for the treatment of adult rheumatoid arthritis and osteoarthritis, has been reported to reduce the formation of polyps in patients with familial adenomatous polyposis. This COX-2 specific inhibitor also protects against experimentally-induced carcinogenesis, but the underlying molecular mechanisms are poorly understood. The present review covers the signal transduction pathways responsible for regulating COX-2 expression as novel molecular targets of chemopreventive agents with celecoxib as a specific example.

  7. Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing and treating pancreatic cancer.

    Science.gov (United States)

    Sarkar, S; Azab, B M; Das, S K; Quinn, B A; Shen, X; Dash, R; Emdad, L; Thomas, S; Dasgupta, S; Su, Z-Z; Wang, X-Y; Sarkar, D; Fisher, P B

    2013-08-01

    Pancreatic cancer remains one of the deadliest of all cancers despite aggressive surgical treatment combined with adjuvant radiotherapy and chemotherapy. Chemoresistance and radioresistance are the principal causes of failure of pancreatic cancer patients to respond to therapy. Conditionally replication competent adenovirus (CRCA)-based cancer gene therapy is an innovative strategy for treating cancers displaying inherent resistance to treatment. Limitations of current adenovirus (Ad)-based gene therapies for malignant tumors include lack of cancer-specificity, and effective and targeted delivery. To remedy this situation, CRCAs have been designed that express E1A, necessary for Ad replication, under the control of a cancer-specific progression elevated gene-3 promoter (PEG-Prom) with concomitant expression of an immunomodulatory cytokine, such as mda-7/IL-24 or interferon-γ (IFN-γ), under the control of a ubiquitous and strong cytomegalovirus promoter (CMV-Prom) from the E3 region. These bipartite CRCAs, when armed with a transgene, are called cancer terminator viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-γ (CTV-γ), because of their universal effectiveness in cancer treatment irrespective of p53/pRb/p16 or other genetic alterations in tumor cells. In addition to their selective oncolytic effects in tumor cells, the potent 'bystander antitumor' properties of MDA-7/IL-24 and IFN-γ embody the CTVs with expanded treatment properties for both primary and distant cancers. Pancreatic cancer cells display a "translational block" of mda-7/IL-24 mRNA, limiting production of MDA-7/IL-24 protein and cancer-specific apoptosis. Specific chemopreventive agents abrogate this "translational block" resulting in pancreatic cancer-specific killing. This novel chemoprevention gene therapy (CGT) strategy holds promise for both prevention and treatment of pancreatic cancers where all other strategies have proven ineffective.

  8. Learning frameworks as an alternative to repositories

    DEFF Research Database (Denmark)

    Dalsgaard, Christian

    2005-01-01

    This paper presents the concept of ‘learning frameworks’. The purpose of the paper is to discuss and question collections of digital learning objects in large repositories and to argue for large learning frameworks which organise a number of thematically related digital learning materials. Whereas...... a learning object repository contains all kinds of materials, a learning framework consists of an organisation of materials related to a common theme. Further, a repository consists of single, self-contained objects, whereas a learning framework is an open-ended environment which presents a number...

  9. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice.

    Science.gov (United States)

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W; Kumar, Nagi; Park, Jong Y

    2014-04-01

    Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. A total of 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of 3 doses of Polyphenon E (200, 500, and 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed before treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22, and 32 weeks old. The number and size of tumors in treated TRAMP mice were significantly decreased compared with untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared with 13% of mice (2/16) treated with high-dose Polyphenon E during the same period. Furthermore, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P = 0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of prostate cancer.

  10. Will salt repositories be dry?

    Science.gov (United States)

    Bredehoeft, John D.

    The National Academy of Science committee that considered geologic disposal of nuclear waste in the mid-1950s recommended salt as a repository medium, partly because of its high thermal conductivity and because it was believed to be “dry” (perhaps the appropriate thought is “impermeable”). Certainly, the fact that Paleozoic salt deposits exist in many parts of t h e world is evidence for very low rates of dissolution by moving groundwater. The fact that the dissolution rates were so small led many scientists to the conclusion that the salt beds were nearly impermeable. The major source of brine within the salt beds was thought to be fluid inclusions within salt crystals, which could migrate through differential solution toward a source of high heat. The idea that salt was uniformly “dry” was revised when exploratory drilling in the vicinity of the Waste Isolation Pilot Plant (WIPP) in New Mexico encountered brines within the Castile Formation, an evaporite deposit below the Salado Formation. The brine reservoirs were thought to be isolated pockets of brine in an otherwise “impermeable” salt section.

  11. Salt Repository Project Repository (WBS 1. 3. 4) Program Plan: Draft

    Energy Technology Data Exchange (ETDEWEB)

    Kingsley, R.S.; Hume, H.R.; McNulty, E.G.

    1986-06-01

    This program plan will describe Salt Repository Project activities conducted under the repository Work Breakdown Structure element. The plan will describe those activities occurring from FY 1986 through the license application in 1991. During this period, the SRP program has three main objectives involving WBS. These include developing repository designs to the extent necessary to support the preparation of the principal licensing documents, the license application, and the final repository site selection report; conducting the RandD studies necessary to support repository design, licensing, and postclosure performance assessment; and analyzing the postclosure performance and waste isolation capabilities of the repository design. Meeting these objectives will require close coordination among all SRP WBS elements. 23 refs., 1 fig., 27 tabs.

  12. NIMH Repository and Genomics Resources (RGR)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIMH Repository and Genomics Resource (RGR) stores biosamples, genetic, pedigree and clinical data collected in designated NIMH-funded human subject studies. The...

  13. Biospecimen Repository Access and Data Sharing (BRADS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BRADS is a repository for data and biospecimens from population health research initiatives and clinical or interventional trials designed and implemented by NICHD’s...

  14. Arsenic immunotoxicity and immunomodulation by phytochemicals: potential relations to develop chemopreventive approaches.

    Science.gov (United States)

    Ramos Elizagaray, Sabina I; Soria, Elio A

    2014-01-01

    Arsenic (As) contaminates drinking water worldwide, and As exposure, hypersensitivity and deficiency are involved in the immunopathogenesis of various health problems. Its chemoprevention thus has a high health impact. Given its oxidative potential, antioxidant compounds are good candidates to counteract arsenic's deleterious effects on humans. Phytochemicals (e.g., phenolics, carotenoids, etc.) act through free radical chelation activity and regulation of cellular targets. Consequently, they are appropriate for developing anti-As strategies derived from plants, and Argentinean flora is rich in useful species. Several molecular pathways involved in immune regulation are at the same time targets of exogenous agents, and oxidative stress itself is a modulating phenomenon of immunity. Since xenohormesis has been described as the organic enhancement of resistance to stress conditions (e.g., oxidation, pollution, etc.) by consuming xenobiotics, immunoxenohormesis implies also defense improvement. This review focuses on recent patents on the development of vegetable redox-related immunomodulating agents, which might be applied in As-induced dysfunctions, with their scientific basis being reviewed.

  15. Nitroxides as antioxidants – possibilities of their application in chemoprevention and radioprotection

    Directory of Open Access Journals (Sweden)

    Sabina Tabaczar

    2011-01-01

    Full Text Available Nitroxides as stabile organic radicals were used initially as spin labels in spectroscopy of electron paramagnetic resonance (EPR with respect to parameters such as pH of an intercellular environment, oxygenation of cells and tissues, fluidity of biological membranes, conformational state and topography of proteins. Nitroxides have also been used in biology and medicine as contrast agents in magnetic resonance imaging (MRI. When their antioxidant activities were discovered, an era of research on the potential utility of these agents began. Nitroxides can modulate the redox state of the cell by participation in oxidation/reduction reactions. Therefore, they are extensively examined in various models of oxidative stress. The antioxidant effect of nitroxides is a result of their ability to catalyze dismutation of superoxide radical (superoxide dismutase-like activity, inhibit lipid peroxidation, prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidative state, and confer catalase-like activity on heme proteins. In the present paper the antioxidative mechanisms of nitroxides are presented. The relation between structure, function and the rate of nitroxide reduction inside cells and tissues is also presented. The application of nitroxides in chemoprevention and radioprotection is discussed.

  16. Learning object repositories as knowledge management systems

    OpenAIRE

    2013-01-01

    Over the past years, a number of international initiatives that recognize the importance of sharing and reusing digital educational resources among educational communities through the use of Learning Object Repositories (LORs) have emerged. Typically, these initiatives focus on collecting digital educational resources that are offered by their creators for open access and potential reuse. Nevertheless, most of the existing LORs are designed more as digital repositories, rather than as Knowled...

  17. Supporting multiple domains in a single reuse repository

    Science.gov (United States)

    Eichmann, David

    1992-01-01

    Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.

  18. Implications for chemoprevention of prostate cancer with intake of cruciferous vegetables

    Institute of Scientific and Technical Information of China (English)

    Jeanny B Aragon-Ching

    2011-01-01

    @@ Efforts on chemoprevention have been an attractive target of investigation for prostate cancer.Since prostate cancer is the most common non-cutaneous malignancy among American men, efforts for chemopreventative strategies make sense.However, such undertaking has been wrought with problems and wide-scale efforts to launch drug chemoprevention have been dampened by mixed results.

  19. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  20. Monitored Geologic Repository Test Evaluation Plan

    Energy Technology Data Exchange (ETDEWEB)

    M.B. Skorska

    2002-01-02

    The Monitored Geologic Repository test & evaluation program will specify tests, demonstrations, examinations, and analyses, and describe procedures to conduct and document testing necessary to verify meeting Monitored Geologic Repository requirements for a safe and effective geologic repository for radioactive waste. This test program will provide assurance that the repository is performing as designed, and that the barriers perform as expected; it will also develop supporting documentation to support the licensing process and to demonstrate compliance with codes, standards, and regulations. This comprehensive program addresses all aspects of verification from the development of test requirements to the performance of tests and reporting of the test results. The ''Monitored Geologic Repository Test & Evaluation Plan'' provides a detailed description of the test program approach necessary to achieve the above test program objectives. This test plan incorporates a set of test phases focused on ensuring repository safety and operational readiness and implements a project-wide integrated product management team approach to facilitate test program planning, analysis, and implementation. The following sections provide a description of the individual test phases, the methodology for test program planning and analyses, and the management approach for implementing these activities.

  1. Implementation of the Brazilian national repository

    Energy Technology Data Exchange (ETDEWEB)

    Tello, Cledola Cassia Oliveira de, E-mail: tellocc@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    Ionizing radiation in Brazil is used in electricity generation, medicine, industry, agriculture and for research and development purposes. All these activities can generate radioactive waste. At this point, in Brazil, the use of nuclear energy and radioisotopes justifies the construction of a national repository for radioactive wastes of low and intermediate-level. According to Federal Law No. 10308, Brazilian National Commission for Nuclear Energy (CNEN) is responsible for designing and constructing the intermediate and final storages for radioactive wastes. Additionally, a restriction on the construction of Angra 3 is that the repository is under construction until its operation start, attaining some requirements of the Brazilian Environmental Regulator (IBAMA). The RBMN Project (Repository for Low and Intermediate-Level Radioactive Wastes) aims at the implantation of a National Repository for disposal of low and intermediate-level of radiation wastes. This Project has some aspects that are unique in the Brazilian context, especially referring to the time between its construction and the end of its institutional period. This time is about 360 years, when the area will be released for unrestricted uses. It means that the Repository must be safe and secure for more than three hundred years, which is longer than half of the whole of Brazilian history. This aspect is very new for the Brazilian people, bringing a new dimension to public acceptance. Another point is this will be the first repository in South America, bringing a real challenge for the continent. The current status of the Project is summarized. (author)

  2. Raman spectroscopic investigation of the chemopreventive response of naringenin and its nanoparticles in DMBA-induced oral carcinogenesis

    Science.gov (United States)

    Krishnakumar, N.; Sulfikkarali, N. K.; Manoharan, S.; Venkatachalam, P.

    2013-11-01

    Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the biomolecular changes associated with tumor progression. The aim of the present study is to investigate the biomolecular changes in chemopreventive response of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) during 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by Fourier Transform Raman (FT-Raman) spectroscopy. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Raman spectra differed significantly between the control and tumor tissues, with tumors showing higher percentage signals for nucleic acids, phenylalanine and tryptophan and a lower in the percentage of phospholipids. Moreover, oral administration of free NAR and NARNPs significantly increased phospholipids and decreased the levels of tryptophan, phenylalanine and nucleic acid contents. On a comparative basis, NARNPs was found to have a more potent antitumor effect than free NAR in completely preventing the formation of squamous cell carcinoma and in improving the biochemical status to a normal range in DMBA-induced oral carcinogenesis. The present study further suggest that Raman spectroscopy could be a valuable tool for rapid and sensitive detection of specific biomolecular changes in response to chemopreventive agents.

  3. Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways.

    Science.gov (United States)

    Siddiqi, Aisha; Hasan, Syed Kazim; Nafees, Sana; Rashid, Summya; Saidullah, Bano; Sultana, Sarwat

    2015-12-01

    In the present study, chemopreventive efficacy of hesperidin was evaluated against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in wistar rats. Nephrotoxicity was induced by single intraperitoneal injection of Fe-NTA (9 mg Fe/kg b.wt). Renal cancer was initiated by the administration of N-nitrosodiethylamine (DEN 200mg/kg b.wt ip) and promoted by Fe-NTA (9 mg Fe/kg b.wt ip) twice weekly for 16 weeks. Efficacy of hesperidin against Fe-NTA-induced nephrotoxicity was assessed in terms of biochemical estimation of antioxidant enzyme activities viz. reduced renal GSH, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, superoxide dismutase and renal toxicity markers (BUN, Creatinine, KIM-1). Administration of Fe-NTA significantly depleted antioxidant renal armory, enhanced renal lipid peroxidation as well as the levels of BUN, creatinine and KIM-1. However, simultaneous pretreatment of hesperidin restored their levels in a dose dependent manner. Expression of apoptotic markers caspase-3, caspase-9, bax, bcl-2 and proliferative marker PCNA along with inflammatory markers (NFκB, iNOS, TNF-α) were also analysed to assess the chemopreventive potential of hesperidin in two-stage renal carcinogenesis model. Hesperidin was found to induce caspase-3, caspase-9, bax expression and downregulate bcl-2, NFκB, iNOS, TNF-α, PCNA expression. Histopathological findings further revealed hesperidin's chemopreventive efficacy by restoring the renal morphology. Our results provide a powerful evidence suggesting hesperidin to be a potent chemopreventive agent against renal carcinogenesis possibly by virtue of its antioxidant properties and by modulation of multiple molecular pathways.

  4. Tea beverage in chemoprevention and chemotherapy of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Imtiaz A SIDDIQUI; Mohammad SALEEM; Vaqar M ADHAMI; Mohammad ASIM; Hasan MUKHTAR

    2007-01-01

    Prostate cancer (Pca) is the most frequently diagnosed malignancy and the sec-ond leading cause of cancer-related deaths in American males with similar trends in many western countries. The existing treatment approaches and surgical inter-vention have not been able to effectively cope with this dreaded disease. For these reasons, it is necessary to intensify our efforts for a better understanding of the disease process and for the development of novel approaches for its preven-tion and treatment. Based on considerable evidence from in vivo and in vitro data and epidemiological studies, in recent years the beverage tea has gained consid-erable attention for reducing the risk of several cancers. Much of the cancerpreventive effects of tea, especially green tea appear to be mediated by the polyphe-nols present therein. Geographical evidence suggests that the incidence and occurrence of Pca is lower in populations that consume tea regularly. This evi-dence suggests that tea polyphenols could be extrapolated to optimize their chemopreventive properties against Pca. Pca represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age and therefore, even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. In this review we address the issue of possible use of tea, especially green tea, for the prevention aswell as treatment of Pca.

  5. SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    D.C. Randle

    2000-01-07

    The primary purpose of this document is to develop a preliminary high-level functional and physical control system architecture for the potential repository at Yucca Mountain. This document outlines an overall control system concept that encompasses and integrates the many diverse process and communication systems being developed for the subsurface repository design. This document presents integrated design concepts for monitoring and controlling the diverse set of subsurface operations. The Subsurface Repository Integrated Control System design will be composed of a series of diverse process systems and communication networks. The subsurface repository design contains many systems related to instrumentation and control (I&C) for both repository development and waste emplacement operations. These systems include waste emplacement, waste retrieval, ventilation, radiological and air monitoring, rail transportation, construction development, utility systems (electrical, lighting, water, compressed air, etc.), fire protection, backfill emplacement, and performance confirmation. Each of these systems involves some level of I&C and will typically be integrated over a data communications network throughout the subsurface facility. The subsurface I&C systems will also interface with multiple surface-based systems such as site operations, rail transportation, security and safeguards, and electrical/piped utilities. In addition to the I&C systems, the subsurface repository design also contains systems related to voice and video communications. The components for each of these systems will be distributed and linked over voice and video communication networks throughout the subsurface facility. The scope and primary objectives of this design analysis are to: (1) Identify preliminary system-level functions and interfaces (Section 6.2). (2) Examine the overall system complexity and determine how and on what levels the engineered process systems will be monitored, controlled, and

  6. Fons antic i repositoris universitaris a Espanya

    Directory of Open Access Journals (Sweden)

    Herrera Morillas, José Luis

    2015-12-01

    Full Text Available Es mostra la presència de col·leccions de fons antic en els repositoris de les biblioteques universitàries espanyoles després d'analitzar tots els repositoris. Per a aquesta anàlisi, com a part de la metodologia emprada, s'ha elaborat un model o llista que consta d'onze elements. Del conjunt de les universitats espanyoles, seixanta tenen repositoris, vint-i-vuit dels quals (16,8 % disposen de col·leccions de fons antic. Com que del concepte de repositori institucional no sembla desprendre's que tingui com a finalitat incloure aquest tipus de col·leccions, es reflexiona sobre la peculiaritat que una part dels repositoris universitaris espanyols inclogui col·leccions d'aquestes característiques.Se muestra la presencia de colecciones de fondo antiguo en los repositorios de las bibliotecas universitarias españolas después de analizar todos los repositorios. Para este análisis, como parte de la metodología empleada, se ha elaborado un modelo o lista que consta de once elementos. Del conjunto de las universidades españolas, sesenta cuentan con repositorios y, de estos, veintiocho (16,8 % disponen de colecciones de fondo antiguo. Debido a que del concepto de repositorio institucional no parece desprenderse que tenga como finalidad albergar este tipo de colecciones, se hace una reflexión sobre la peculiaridad de que parte de los repositorios universitarios españoles incluya colecciones de estas características.This paper uses an analysis of the repositories of Spanish universities to identify which institutions contain rare book and manuscript collections. The method used in this analysis involved examining each university on the basis of a list comprising eleven elements. A total of 60 universities were found to have repositories but only 28 (16.8 % of these contained rare book and manuscript collections. In the light of these figures, which suggest that Spanish university repositories do not generally consider the preservation of rare

  7. Analysis of computational vulnerabilities in digital repositories

    Directory of Open Access Journals (Sweden)

    Valdete Fernandes Belarmino

    2015-04-01

    Full Text Available Objective. Demonstrates the results of research that aimed to analyze the computational vulnerabilities of digital directories in public Universities. Argues the relevance of information in contemporary societies like an invaluable resource, emphasizing scientific information as an essential element to constitute scientific progress. Characterizes the emergence of Digital Repositories and highlights its use in academic environment to preserve, promote, disseminate and encourage the scientific production. Describes the main software for the construction of digital repositories. Method. The investigation identified and analyzed the vulnerabilities that are exposed the digital repositories using Penetration Testing running. Discriminating the levels of risk and the types of vulnerabilities. Results. From a sample of 30 repositories, we could examine 20, identified that: 5% of the repositories have critical vulnerabilities, 85% high, 25% medium and 100% lowers. Conclusions. Which demonstrates the necessity to adapt actions for these environments that promote informational security to minimizing the incidence of external and / or internal systems attacks.Abstract Grey Text – use bold for subheadings when needed.

  8. Web-based tribology design repository system

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tribology design is one of the most important parts of mechanical product design as thestrength design. Unfortunately, because tribology design knowledge is often m ulti-disciplinary,complicated and piecemeal, it is therefore difficult for a mechanical designer to capture the neededtribology design knowledge. The concept of tribology design repository is proposed in this paper totry to address this problem. This paper presents an object-oriented knowledge representation lan-guage based on the modeling of tribology design component and it makes the complicated tribol-ogy knowledge represented has such advantages as inheritance, encapsulation, and consistency.A web-based triblogy design repository is then established and it enables the edition, retrieve,sharing and reuse of corporate tribology design knowledge in the repository from the Internet.

  9. Investigative study of standards for digital repositories and related services

    CERN Document Server

    Foulonneau, Muriel; Badolato, Anne-Marie

    2008-01-01

    This study is meant for institutional repository managers, service providers, repository software developers and generally, all players taking an active part in the creation of the digital repository infrastructure for e-research and e-learning. It reviews the current standards, protocols and applications in the domain of digital repositories. Special attention is being paid to the interoperability of repositories to enhance the exchange of data in repositories. It aims to stimulate discussion about these topics and supports initiatives for the integration of and, where needed, development of

  10. GreyGuide Forum and Repository

    OpenAIRE

    Biagioni, Stefania; Farace, Dominic

    2014-01-01

    We present the GreyGuide: an online forum and repository of good practice in the field of grey literature. The launch of the GreyGuide Repository took place in December 2013 at the Fifteenth International Conference on Grey Literature. Since then, the acquisition of both proposed and published good practices are underway. The GreyGuide as an online forum is currently in a developmental stage and is influenced by the changes that have taken place in GreyNet's new infrastructure commencing in J...

  11. Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Peramaiyan Rajendran

    2014-01-01

    Full Text Available Aim of the Study: In the present study the effects of mangiferin were tested against lung cancer-bearing mice in both the pre-initiation and post-initiation periods. Materials and Methods: Healthy male Swiss albino mice (6-8 weeks old were used throughout the study. The animals were treated with mangiferin (100 mg/kg body weight dissolved in corn oil two weeks before (pre-initiation and the twelfth week after (post-initiation the establishment of B (a P (50 mg/kg body weight-induced lung carcinoma. Results: The body weight decreased and the lung weight and levels of xenobiotic and liver marker enzymes markedly increased in the carcinogen-administered animals; and mangiferin treatment brought the values of these parameters back to the near-normal ones. The activities of lysosomal enzymes in the animals with B (a P-induced experimental lung carcinogenesis were also assessed. In these animals there was an increase in the activities of lysosomal enzymes such as acidphosphatase, β-glucuronidase, N-acetyl glucosaminidase, and β-galactosidase. Conclusion: Supplementation with mangiferin attenuated all these alterations, thus indicating its anticancer effect. Overall, the above data showed that the anticancer effect of mangiferin as a chemopreventive agent was pronounced.

  12. Cytochrome P450 1B1, a novel chemopreventive target for benzo[a]pyrene-initiated human esophageal cancer.

    Science.gov (United States)

    Wen, Xia; Walle, Thomas

    2007-02-08

    Esophageal cancer is common worldwide, with poor prognosis. Smoking, including exposure to polyaromatic hydrocarbons like benzo[a]pyrene (BaP), is a major risk factor. In human esophageal HET-1A cells, we found that time-dependent BaP-DNA binding was associated with upregulation of CYP1B1, but not CYP1A1, mRNA and protein. The dietary flavonoid 5,7-dimethoxyflavone significantly inhibited BaP-DNA binding and down-regulated BaP-induced CYP1B1 mRNA and protein. 3',4'-Dimethoxyflavone was an even more potent inhibitor of CYP1B1 expression, while resveratrol had no effect. Thus, dietary methoxylated flavones inhibited BaP-induced CYP1B1 transcription in a cell-specific manner and hold promise as chemopreventive agents in esophageal carcinogenesis.

  13. 肺癌化学药物预防的研究进展%Research progress on lung cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    刘乾; 徐卫国

    2014-01-01

    肺癌是世界范围内癌症致死的首要原因。近年来,针对肺癌的传统治疗手段虽不断发展和改善,但肺癌的病死率未明显改变。除了大力倡导戒烟,化学药物预防有望降低肺癌的发生及抑制肺癌的发展,从而成为近年来研究的热点。化学药物预防是应用饮食和/或药物来抑制或逆转肿瘤的形成,目前已成功用于某些恶性肿瘤的临床预防。虽然已有的研究未能找到有效预防肺癌的药物,但鉴于大部分肺癌的发生是支气管上皮经历正常分化、增生、化生、异常增生及癌变的过程,故找寻可以有效抑制或逆转癌前病变或癌前状态的药物就变得愈发重要。%Lung cancer is the leading cause of cancer death in the world.Most patients with lung cancer are not candidates for curative therapy,and new therapies have not made a substantial impact on survival.Chemoprevention can reverse or inhibit the carcinogenic process through the use of dietary or pharmaceutical agents and has been successfully applied to common malignancies other than lung.Despite previous studies in lung cancer chemoprevention failing to identify effective agents,since the development of most lung bronchogenic carcinoma in the central bronchial epithelium starts with normal epithelium and progresses through hyperplasia,metaplasia,dysplasia,carcinoma in situ to invasive lung cancer.It is needed for effective lung cancer chemoprevention to reverse or inhibit the premalignant lesions.

  14. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions

    Institute of Scientific and Technical Information of China (English)

    Margie Lee CLAPPER; Harry Stanley COOPER; Wen-Chi Lee CHANG

    2007-01-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) -induced colitis represents an excellent preclinical system in which to both charac-terize the molecular events required for tumor formation in the presence of inflam-marion and assess the ability of select agents to inhibit this process. Cyclic admin-istration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological fea-tures that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen(azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc),p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a pre-ventable disease.

  15. Structuring and presenting annotated media repositories

    NARCIS (Netherlands)

    Rutledge, L.; Ossenbruggen, J.R. van; Hardman, L.

    2004-01-01

    The Semantic Web envisions a Web that is both human readable and machine processible. In practice, however, there is still a large conceptual gap between annotated content repositories on the one hand, and coherent, human readable Web pages on the other. To bridge this conceptual gap, one needs to s

  16. New Quantitative Study for Dissertations Repository System

    CERN Document Server

    Alshammari, Fahad H; Zaidan, M A; Hmood, Ali K; Zaidan, B B; Zaidan, A A

    2010-01-01

    In the age of technology, the information communication technology becomes very important especially in education field. Students must be allowed to learn anytime, anywhere and at their own place. The facility of library in the university should be developed. In this paper we are going to present new Quantitative Study for Dissertations Repository System and also recommend future application of the approach.

  17. Two-dimensional magma-repository interactions

    NARCIS (Netherlands)

    Bokhove, O.

    2001-01-01

    Two-dimensional simulations of magma-repository interactions reveal that the three phases --a shock tube, shock reflection and amplification, and shock attenuation and decay phase-- in a one-dimensional flow tube model have a precursor. This newly identified phase ``zero'' consists of the impact of

  18. Sharing Data between LSDBs and Central Repositories

    NARCIS (Netherlands)

    den Dunnen, Johan T.; Sijmons, Rolf H.; Andersen, Paal S.; Vihinen, Mauno; Beckmann, Jacques S.; Rossetti, Sandro; Talbot, C. Conover; Hardison, Ross C.; Povey, Sue; Cotton, Richard G. H.

    2009-01-01

    Several Locus-Specific DataBases (LSDBs) have recently been approached by larger, more general data repositories (including NCBI and UCSC) with the request to share the DNA variant data they have collected. Within the Human Genome Variation Society (HGVS) a document was generated summarizing the iss

  19. Refactoring Process Models in Large Process Repositories.

    NARCIS (Netherlands)

    Weber, B.; Reichert, M.U.

    2008-01-01

    With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are introdu

  20. Ontology-based Software Repository System

    Science.gov (United States)

    2010-04-30

    and domains. Current State of the Art Improvements to the current state of the art for software reuse repositories are required ( Shiva & Shala, 2007...model of architecture. IEEE Software, 12(6), 42-50. Object Management Group. (2005). Reusable asset specification (Vers. 2.2). Shiva , S., & Shala

  1. Siting Patterns of Nuclear Waste Repositories.

    Science.gov (United States)

    Solomon, Barry D.; Shelley, Fred M.

    1988-01-01

    Provides an inventory of international radioactive waste-management policies and repository siting decisions for North America, Central and South America, Europe, Asia, and Africa. This discussion stresses the important role of demographic, geologic, and political factors in siting decisions. (Author/BSR)

  2. Visual querying and analysis of large software repositories

    NARCIS (Netherlands)

    Voinea, Lucian; Telea, Alexandru

    2009-01-01

    We present a software framework for mining software repositories. Our extensible framework enables the integration of data extraction from repositories with data analysis and interactive visualization. We demonstrate the applicability of the framework by presenting several case studies performed on

  3. Open DOAR the Directory of Open Access Repositories

    CERN Document Server

    CERN. Geneva

    2005-01-01

    The last year has seen wide-spread growth in the idea of using open access repositories as a part of a research institution's accepted infrastructure. Policy development from institutions and funding bodies has also supported the growth of the repository network. The next stage of expansion will be in the provision of services and cross-repository facilities and resources. Of course, it is hoped that these will then establish a feed-back loop to encourage repository population and further repository establishment, as the potential of open access to research materials is realised. The growth of repositories has been organic, with a variety of different repositories based in departments, institutions, funding agencies or subject communities, with a range of content, both in type and subject. Existing repositories are expanding their holdings, from eprints to associated research data-sets, or with learning objects and multimedia material. This presentation will look at the development of the Directory of Open Ac...

  4. Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

    NARCIS (Netherlands)

    Breda, van S.G.; Wilms, L.C.; Gaj, S.; Briedé, J.J.; Helsper, J.P.F.G.; Kleinjans, J.C.; Kok, de T.M.

    2014-01-01

    Blueberries contain relatively large amounts of different phytochemicals which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans

  5. The repository ecology an approach to understanding repository and service interactions

    CERN Document Server

    CERN. Geneva; Hagemann, Melissa

    2007-01-01

    An increasing number of university institutions and other organisations are deciding to deploy repositories and a growing number of formal and informal distributed services are supporting or capitalising on the information these repositories provide. Despite reasonably well understood technical architectures, early majority adopters may struggle to articulate their place within the actualities of a wider information environment. The idea of a repository ecology provides developers and administrators with a useful way of articulating and analysing their place in the information environment, and the technical and organisational interactions they have, or are developing, with other parts of such an environment. This presentation will provide an overview of the concept of a repository ecology and examine some examples from the domains of scholarly communications and elearning.

  6. The repository ecology: an approach to understanding repository and service interactions

    CERN Document Server

    CERN. Geneva

    2007-01-01

    An increasing number of university institutions and other organisations are deciding to deploy repositories and a growing number of formal and informal distributed services are supporting or capitalising on the information these repositories provide. Despite reasonably well understood technical architectures, early majority adopters may struggle to articulate their place within the actualities of a wider information environment. The idea of a repository ecology provides developers and administrators with a useful way of articulating and analysing their place in the information environment, and the technical and organisational interactions they have, or are developing, with other parts of such an environment. This presentation will provide an overview of the concept of a repository ecology and examine some examples from the domains of scholarly communications and elearning. View John Robertson's biography

  7. Investigative study of standards for Digital Repositories and related services

    NARCIS (Netherlands)

    Foulonneau, Muriel; André, Francis

    2007-01-01

    This study is meant for institutional repository managers, service providers, repository software developers and generally, all players taking an active part in the creation of the digital repository infrastructure for e-research and e-learning. It reviews the current standards, protocols and applic

  8. Institutional Repositories in Indian Universities and Research Institutes: A Study

    Science.gov (United States)

    Krishnamurthy, M.; Kemparaju, T. D.

    2011-01-01

    Purpose: The purpose of this paper is to report on a study of the institutional repositories (IRs) in use in Indian universities and research institutes. Design/methodology/approach: Repositories in various institutions in India were accessed and described in a standardised way. Findings: The 20 repositories studied covered collections of diverse…

  9. Repositories for Research: Southampton's Evolving Role in the Knowledge Cycle

    Science.gov (United States)

    Simpson, Pauline; Hey, Jessie

    2006-01-01

    Purpose: To provide an overview of how open access (OA) repositories have grown to take a premier place in the e-research knowledge cycle and offer Southampton's route from project to sustainable institutional repository. Design/methodology/approach: The evolution of institutional repositories and OA is outlined raising questions of multiplicity…

  10. Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Richard M NILES

    2007-01-01

    Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabo-lisrn/action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second prima-ties in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unrespon-sive premalignant lesions.

  11. Design aspects of the alpha repository. II. Conceptual layouts of underground storage facilities

    Energy Technology Data Exchange (ETDEWEB)

    Grams, W.H.

    1975-06-30

    Five conceptual repository layouts are presented: linear repository, 1 panel; bow tie repository, 2 panels; maltese cross repository, 4 panels; snowflake repository; 5 panels, and sash window repository, 8 panels. The layouts are compared with respect to excavation requirements, haulage distances, ventilation flow path designs, and safety features. (LK)

  12. Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention.

    Science.gov (United States)

    Earnest, D L; Hixson, L J; Alberts, D S

    1992-01-01

    Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in

  13. Digital Repository of Research Institutes – RCIN

    Directory of Open Access Journals (Sweden)

    Kamila Kaczyńska

    2014-03-01

    Full Text Available The paper describes the project of Digital Repository of Scientific Institutes RCIN and presents opportunities for promoting science by digitization and sharing them on the Internet. The Repository has been created by the 16 Scientific Institutes in Warsaw, Krakow and Bialowieza to modernize the science-research and IT infrastructure, to increase digital resources of mathematical, technical, natural and medical sciences, and to popularize and promote of Polish science. That dissemination and popularization of science affects its development and competitiveness in the international arena and it allows transfer of research results to the economy. In addition, Institutes of RCIN providing contemporary and archival materials of science, support the intellectual capital of Polish science and raise awareness of professional literature of search on the Internet. Project RCIN is implemented in the years 2010–2014 and financing is provided by the funds of the European Fund of Regional Development.

  14. Bedded-salt repository analysis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Guiffre, M.S.; Kaplan, M.F.; Ensminger, D.A.; Oston, S.G.; Nalbandian, J.Y.

    1980-03-31

    This report contains a description of an analysis of generic nuclear waste repository in bedded salt. This analysis was performed by TASC for inclusion in a major Lawrence Livermore Laboratory report to NRC; this report therefore should be viewed as providing more complete and detailed information about this analysis than was possible to include in the LLL report. The analysis is performed with the NUTRAN computer codes which are described in the report. The model to be analyzed is defined, and the results of a series of possible waste migration scenarios are presented. Several of these scenarios are used as the basis for a sensitivity analysis, and an uncertainty analysis utilizing Monte Carlo techniques is also performed. A new method for defining the consequences to users of a well drilled near the repository is also described, and results are presented based on two of the waste migration scenarios.

  15. Managing an Institutional Repository with CDS Invenio

    CERN Document Server

    Robinson, N; Simko, T

    2007-01-01

    CERN has long been committed to the free dissemination of scientific research results and theories. Towards this end, CERN's own institutional repository, the CERN Document Server (CDS) offers access to CERN works and to all related scholarly literature in the HEP domain. Hosting over 500 document collections containing more than 900,000 records, CDS provides access to anything from preprints and articles, to multimedia information such as photographs, movies, posters and brochures. The software that powers this service, CDS Invenio, is distributed freely under the GNU GPL and is currently used in approximately 15 institutions worldwide. In this paper, we discuss the use of CDS Invenio to manage a repository of scientific literature. We outline some of the issues faced during the lifecycle of a document from acquisition, processing and indexing to dissemination. In particular, we focus on the features and technology developed to meet the complexities of managing scientific information in the LHC era of large ...

  16. Numerical modeling capabilities to predict repository performance

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    This report presents a summary of current numerical modeling capabilities that are applicable to the design and performance evaluation of underground repositories for the storage of nuclear waste. The report includes codes that are available in-house, within Golder Associates and Lawrence Livermore Laboratories; as well as those that are generally available within the industry and universities. The first listing of programs are in-house codes in the subject areas of hydrology, solute transport, thermal and mechanical stress analysis, and structural geology. The second listing of programs are divided by subject into the following categories: site selection, structural geology, mine structural design, mine ventilation, hydrology, and mine design/construction/operation. These programs are not specifically designed for use in the design and evaluation of an underground repository for nuclear waste; but several or most of them may be so used.

  17. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    Science.gov (United States)

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-05

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.

  18. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention.

    Science.gov (United States)

    Paonessa, Joseph D; Ding, Yi; Randall, Kristen L; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-06-01

    NF-E2-related factor 2 (Nrf2) is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. Although Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2(+/+) mice than in Nrf2(-/-) mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. Although glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, although higher liver UGT activity may protect the liver against ABP, it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further show that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues but does not seem to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2.

  19. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    Science.gov (United States)

    Sulfikkarali, N. K.; Krishnakumar, N.

    2013-04-01

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350-700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents.

  20. Dissertations Repository System Using Context Module

    CERN Document Server

    Hmood, Ali K; Alanazi, Hamdan O; Alnaqeib, Rami; Al-Nabhani, Yahya

    2010-01-01

    Without a doubt, the electronic learning makes education quite flexible. Nowadays, all organizations and institutions are trying to avoid Monotony and the delay and inertia. As well the universities should be improving their systems continually to achieve success. Whereas, the students need to access the dissertations in the library. In this paper we will present Dissertations Repository System Using Context Module to allow the students to benefit the dissertations which is in the library flexibly.

  1. Repository-based software engineering program

    Science.gov (United States)

    Wilson, James

    1992-01-01

    The activities performed during September 1992 in support of Tasks 01 and 02 of the Repository-Based Software Engineering Program are outlined. The recommendations and implementation strategy defined at the September 9-10 meeting of the Reuse Acquisition Action Team (RAAT) are attached along with the viewgraphs and reference information presented at the Institute for Defense Analyses brief on legal and patent issues related to software reuse.

  2. The once & future repository, HKU's Scholars Hub

    OpenAIRE

    Palmer, DT; Castro, P.; Bollini, A; Mennielli, M

    2015-01-01

    The HKU Scholars Hub (the Hub) began service as a traditional institutional repository of The University of Hong Kong (HKU). However this format was not compelling to HKU researchers. Fortunately a subsequent reformation of the HKU statement on university mission and vision infused new life and purpose into the project. Over the next five years, in partnership with the Italian University Consortium, Cineca, the HKU Libraries transformed the Hub from an IR to a Current Research Information ...

  3. Institutional Repositories in India: A preliminary study

    OpenAIRE

    2011-01-01

    This preliminary study investigates various aspects of institutional repositories (IR’s) developed in India. The present study has identified the existence of 16 functional IRs some of which were not registered in any of the directories such as ROAR, Open DOAR. The study explores the timeline involved in planning, pilot testing, to system implementation of IR, exploratory activities conducted before implementing IR, its anticipated benefits.

  4. Phytochemical Modulators of Mitochondria: The Search for Chemopreventive Agents and Supportive Therapeutics

    Directory of Open Access Journals (Sweden)

    Maja M. Grabacka

    2014-09-01

    Full Text Available Mitochondria are crucially important for maintaining not only the energy homeostasis, but the proper cellular functions in a general sense. Impairment of mitochondrial functions is observed in a broad variety of pathological states such as neoplastic transformations and cancer, neurodegenerative diseases, metabolic disorders and chronic inflammation. Currently, in parallel to the classical drug design approaches, there is an increasing interest in the screening for natural bioactive substances, mainly phytochemicals, in order to develop new therapeutic solutions for the mentioned pathologies. Dietary phytochemicals such as resveratrol, curcumin and sulforaphane are very well tolerated and can effectively complement classical pharmacological therapeutic regimens. In this paper we disscuss the effect of the chosen phytochemicals (e.g., resveratrol, curcumin, sulforaphane on various aspects of mitochondrial biology, namely mitochondrial biogenesis, membrane potential and reactive oxygen species production, signaling to and from the nucleus and unfolded protein response.

  5. Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents.

    Science.gov (United States)

    Bandgar, Babasaheb P; Adsul, Laxman K; Lonikar, Shrikant V; Chavan, Hemant V; Shringare, Sadanand N; Patil, Sachin A; Jalde, Shivkumar S; Koti, Basawaraj A; Dhole, Nagesh A; Gacche, Rajesh N; Shirfule, Amol

    2013-06-01

    A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.

  6. New cytochrome P450 isoforms as cancer biomarkers and targets for chemopreventive and chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    Hanna Szaefer

    2013-08-01

    Full Text Available Cytochromes P450 (P450 are a multigene family of enzymes possessing a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs, and endogenous compounds. The activity of different P450 isoforms varies within specific tissues and cell types and is selectively regulated together with their gene expression. Moreover, differential expression of certain P450 isoforms’ genes in tumor cells compared to normal tissues can be observed. This creates the potential for the use of these isozymes as tumor markers or selective prodrug activators. This article discusses the characteristics and function of five isoforms of cytochrome P450 (P450 1B1, P450 2W1, P450 2S1, P450 2R1, P450 2U1 that could be potential targets for tumor therapeutic and preventive strategies. These isoforms have been chosen because their level of expression in tumor tissues is definitely higher than in normal tissues.

  7. Diallyl trisulfide, a chemopreventive agent from Allium vegetables, inhibits alpha-secretases in breast cancer cells.

    Science.gov (United States)

    Kiesel, Violet A; Stan, Silvia D

    2017-03-18

    Breast cancer affects one in eight women throughout the course of their lifetime creating a demand for novel prevention strategies against this disease. The Notch signaling pathway is often aberrantly activated in human malignancies including breast cancer. Alpha secretases, including ADAM (A Disintegrin and Metalloprotease) -10 and -17, are proteases that play a key role in the cleavage of cell surface molecules and subsequent ligand-mediated activation of Notch signaling pathway. High expression levels of ADAM10 and 17 have been clinically associated with a lower disease-free survival in breast cancer patients. This study was undertaken to determine the effect of diallyl trisulfide (DATS), a bioactive organosulfide found in garlic and other Allium vegetables, on alpha secretases in breast cancer cells. Here we report for the first time that DATS inhibits the expression of ADAM10 and ADAM17 in estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells, and in Harvey-ras (H-Ras) transformed MCF10A-H-Ras breast epithelial cells. We also show that DATS induces a dose-dependent reduction in colony formation ability of MDA-MB-231 and MCF-7 cells, suggesting a long-term effect of DATS on growth inhibition of breast cancer cells. Furthermore, we show that DATS inhibits the Notch ligands Jagged-1 and Jagged-2 involved in activation of Notch signaling pathway. Collectively, these findings show that DATS targets Notch pathway components overexpressed in breast cancer tumors and may serve as a functionally relevant bioactive for breast cancer prevention.

  8. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    Science.gov (United States)

    2003-03-01

    or high-selenium yeast given prior (12) Waters DJ, Sakr WA, Hayden DW, Lang cancer and that were of a comparable CM, McKinney L, Murphy GP , et al...cancer. * Home Defibrillator ADHD Child? Researchers say the results show that selenium may help protect cells within the aging prostate from initial DNA...References: 1. Waters DJ, Sakr WA, Hayden DW, Lang CM, McKinney L, Murphy GP , Radinsky R, Ramoner R, Richardson RC, Tindall DJ. Workgroup 4

  9. Design, synthesis, and computational studies on dihydropyrimidine scaffolds as potential lipoxygenase inhibitors and cancer chemopreventive agents.

    Science.gov (United States)

    Venugopala, Katharigatta N; Govender, Reshme; Khedr, Mohammed A; Venugopala, Rashmi; Aldhubiab, Bandar E; Harsha, Sree; Odhav, Bharti

    2015-01-01

    Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of cancer when compared to normal cells. The development of novel lipoxygenase inhibitors can have a major role in cancer therapy. A series of substituted 1,4-dihydropyrimidine analogues were synthesized and characterized by (1)H-NMR, (13)C-NMR, and HRMS. Molecular docking against lipoxygenase enzyme (protein data bank code =3V99) was done using Molecular Operating Environment 2013.08 and Leadit 2.1.2 softwares and showed high affinities. The synthesized compounds were tested for their lipoxygenase inhibitory activity and showed inhibition ranging from 59.37%±0.66% to 81.19%±0.94%. The activity was explained by a molecular docking study. The title compounds were also tested for cytotoxic activity against two human cancer cell lines Michigan Cancer Foundation-7 and human melanoma cells and a normal peripheral blood mononuclear cell line.

  10. South African Herbal Extracts as Potential Chemopreventive Agents: Screening for Anticancer Splicing Activity.

    Science.gov (United States)

    Dlamini, Zodwa; Mbita, Zukile; Bates, David O; Bates, David

    2016-01-01

    RT-PCR is an invaluable tool for the detection and characterization of mRNA. Cancer cell lines are treated with crude plant extracts and RNA is extracted and purified with DNase prior to RT-PCR. RT-PCR first-strand cDNA synthesis is done using random primers and can be refrigerated at 4 °C. PCR from the stored cDNA is performed using transcript-specific primers and electrophoresed on a molecular grade agarose gel to separate the splice variants.

  11. 1-Alpha Hydroxyvitamin D(5) as a Chemotherapeutic and Possibly Chemopreventive Agent

    Science.gov (United States)

    2007-03-01

    differ, in their side-chain structures. They are classified into five forms [2]; vitamin D2 , ergosterol; D3 , cholecalciferol; D4, 22,23...side chain modifications with no definitive function assigned to them. The overall path of metabolism of vitamin D2 is similar to vitamin D3 with a few...analog of vitamin D2 . On the other hand vitamin D3 or cholecalciferol is modified by either methyl or ethyl group on C-24 position. These vitamin D

  12. Electrochemical Analysis of Natural Chemopreventive Agent (Curcumin) in Extracted Sample and Pharmaceutical Formulation (Short Communication)

    OpenAIRE

    Garima Modi; Pitre, K. S.

    2010-01-01

    Curcumin has anti-oxidative and anticarcinogenic activities. This study shows the electrochemical behaviour of curcumin using polarography, i.e., DC polarography and differential pulse polarography (DPP) methods. In ammonium tartrate as supporting electrolyte, the differential pulse polarogram of curcumin shows two conjugated peaks with peak potential (Ep) -1125 mV and -1275 mV vs SCE. However, the direct current polarogram shows only one polarographic wave with E1/2 which was -1275 mV. The d...

  13. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    Science.gov (United States)

    2001-03-01

    phosphate buffered saline (PBS, without calcium chloride and magnesium chloride), dimethylsulfoxide (DMSO), triton X-100, trizma base, trypan blue...blood (EDTA) and 5 ml of phosphate buffered saline (PBS) were mixed and layered onto the Ficoll/Hypaque gradient. The tubes were centrifuged at 400 x...horizontal gel electrophoresis tank (Fisher, Fair Lawn, NJ) containing freshly prepared alkaline buffer (300 mM NaOH and 1 mM Na2 EDTA, pH > 13

  14. Salt repository project closeout status report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-06-01

    This report provides an overview of the scope and status of the US Department of Energy (DOE`s) Salt Repository Project (SRP) at the time when the project was terminated by the Nuclear Waste Policy Amendments Act of 1987. The report reviews the 10-year program of siting a geologic repository for high-level nuclear waste in rock salt formations. Its purpose is to aid persons interested in the information developed during the course of this effort. Each area is briefly described and the major items of information are noted. This report, the three salt Environmental Assessments, and the Site Characterization Plan are the suggested starting points for any search of the literature and information developed by the program participants. Prior to termination, DOE was preparing to characterize three candidate sites for the first mined geologic repository for the permanent disposal of high-level nuclear waste. The sites were in Nevada, a site in volcanic tuff; Texas, a site in bedded salt (halite); and Washington, a site in basalt. These sites, identified by the screening process described in Chapter 3, were selected from the nine potentially acceptable sites shown on Figure I-1. These sites were identified in accordance with provisions of the Nuclear Waste Policy Act of 1982. 196 refs., 21 figs., 11 tabs.

  15. The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Heidor, Renato [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Furtado, Kelly Silva; Ortega, Juliana Festa [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Oliveira, Tiago Franco de [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Purgatto, Eduardo [Laboratory of Food Chemistry and Biochemistry, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Moreno, Fernando Salvador, E-mail: rmoreno@usp.br [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil)

    2014-04-15

    The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.

  16. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

    Science.gov (United States)

    Kapadia, Govind J; Azuine, Magnus A; Tokuda, Harukuni; Takasaki, Midori; Mukainaka, Teruo; Konoshima, Takao; Nishino, Hoyoku

    2002-06-01

    Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse

  17. Chemistry of transuranium elements in salt-base repository

    Energy Technology Data Exchange (ETDEWEB)

    Borkowski, Marian [Los Alamos National Laboratory; Reed, Donald T [Los Alamos National Laboratory; Lucchini, Jean - Francois [Los Alamos National Laboratory; Richmann, Michael K [Los Alamos National Laboratory; Khaing, H [Los Alamos National Laboratory; Swanson, J [Los Alamos National Laboratory; Ams, D [Los Alamos National Laboratory

    2010-12-02

    The mobility and potential release of actinides into the accessible environment continues to be the key performance assessment concern of nuclear repositories. Actinide, in particular plutonium speciation under the wide range of conditions that can exist in the subsurface is complex and depends strongly on the coupled effects of redox conditions, inorganic/organic complexation, and the extent/nature of aggregation. Understanding the key factors that define the potential for actinide migration is, in this context, an essential and critical part of making and sustaining a licensing case for a nuclear repository. Herein we report on recent progress in a concurrent modeling and experimental study to determine the speciation of plutonium, uranium and americium in high ionic strength Na-CI-Mg brines. This is being done as part of the ongomg recertification effort m the Waste Isolation Pilot Plant (WIPP). The oxidation-state specific solubility of actinides were established in brine as function of pC{sub H+}, brine composition and the presence and absence of organic chelating agents and carbonate. An oxidation-state invariant analog approach using Nd{sup 3+} and Th{sup 4+} was used for An{sup 3+} and An{sup 4+} respectively. These results show that organic ligands and hydrolysis are key factors for An(III) solubility, hydrolysis at pC{sub H+} above 8 is predominate for An(IV) and carbonates are the key factor for U(VI) solubility. The effect of high ionic strength and brine components measured in absence of carbonates leads to measurable increased in overall solubility over analogous low ionic strength groundwater. Less is known about the bioreduction of actinides by halo-tolerant microorganisms, but there is now evidence that bioreduction does occur and is analogous, in many ways, to what occurs with soil bacteria. Results of solubility studies that focus on Pitzer parameter corrections, new species (e.g. borate complexation), and the thermodynamic parameters for

  18. Polyamines and cancer: implications for chemotherapy and chemoprevention.

    Science.gov (United States)

    Nowotarski, Shannon L; Woster, Patrick M; Casero, Robert A

    2013-02-22

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.

  19. Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention.

    Science.gov (United States)

    Battaglia, Valentina; DeStefano Shields, Christina; Murray-Stewart, Tracy; Casero, Robert A

    2014-03-01

    Polyamines, including spermine, spermidine, and the precursor diamine, putrescine, are naturally occurring polycationic alkylamines that are required for eukaryotic cell growth, differentiation, and survival. This absolute requirement for polyamines and the need to maintain intracellular levels within specific ranges require a highly regulated metabolic pathway primed for rapid changes in response to cellular growth signals, environmental changes, and stress. Although the polyamine metabolic pathway is strictly regulated in normal cells, dysregulation of polyamine metabolism is a frequent event in cancer. Recent studies suggest that the polyamine catabolic pathway may be involved in the etiology of some epithelial cancers. The catabolism of spermine to spermidine utilizes either the one-step enzymatic reaction of spermine oxidase (SMO) or the two-step process of spermidine/spermine N (1)-acetyltransferase (SSAT) coupled with the peroxisomal enzyme N (1)-acetylpolyamine oxidase. Both catabolic pathways produce hydrogen peroxide and a reactive aldehyde that are capable of damaging DNA and other critical cellular components. The catabolic pathway also depletes the intracellular concentrations of spermidine and spermine, which are free radical scavengers. Consequently, the polyamine catabolic pathway in general and specifically SMO and SSAT provide exciting new targets for chemoprevention and/or chemotherapy.

  20. Polyamines and cancer: Implications for chemoprevention and chemotherapy

    Science.gov (United States)

    Nowotarski, Shannon L.; Woster, Patrick M.; Casero, Robert A.

    2013-01-01

    Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes and a poorly characterized transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate, and skin cancers, and altered levels of the rate limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway specific drugs, and ongoing clinical trials targeting polyamine biosynthesis. PMID:23432971

  1. Cancer chemoprevention with green tea catechins: from bench to bed.

    Science.gov (United States)

    Shirakami, Yohei; Shimizu, Masahito; Moriwaki, Hisataka

    2012-12-01

    Many epidemiological studies and a large number of experimental studies using a variety of animal models have observed that consumption or administration of green tea appears to exert cancer chemopreventive activity. Based on the results of numerous laboratory cell culture investigations, several mechanisms have been hypothesized to underlie the anti-cancer activity of green tea catechins, especially that of (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active constituent in green tea. These mechanisms include promotion of anti-oxidant activity, inhibition of NF-κB and AP-1, regulation of the cell cycle, inhibition of receptor tyrosine kinase pathways, control of epigenetic modifications, and modulation of the immune system. Several recent interventional studies examining the anti-carcinogenic properties of green tea catechins in humans have yielded promising results that suggest the possibility of their application to human clinical trials. This review article analyzes the results of these studies to explicate the effects of consumption or administration of green tea and its constituents on malignancies observed to date and discuss future directions in this research field.

  2. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)

    Anna HERMAN-ANTOSIEWICZ; Anna A POWOLNY; Shivendra V SINGH

    2007-01-01

    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  3. Chemopreventive effect of apple and berry fruits against colon cancer.

    Science.gov (United States)

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-12-07

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.

  4. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review.

    Science.gov (United States)

    Bhandari, Prasan R

    2015-04-01

    Cancer is one of the most feared diseases globally and there has been a sustained rise in its incidence in both developing and developed countries. Despite the growing therapeutic options for patients with cancer, their efficacy is time-limited and non-curative. Hence to overcome these drawbacks, an incessant screening for superior and safer drugs has been ongoing for numerous decades, resulting in the detection of anti-cancer properties of several phytochemicals. Chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Among the spices, Crocus sativus L. (saffron; fān hóng huā) has generated interest because pharmacological experiments have established numerous beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients. This review provides a brief insight into the anticancer properties of saffron and its components.

  5. Chemopreventive functions and molecular mechanisms of garlic organosulfur compounds.

    Science.gov (United States)

    Trio, Phoebe Zapanta; You, Sixiang; He, Xi; He, Jianhua; Sakao, Kozue; Hou, De-Xing

    2014-05-01

    Garlic (Allium sativum L.) has long been used both for culinary and medicinal purposes by many cultures. Population and preclinical investigations have suggested that dietary garlic intake has health benefits, such as lowering the risk of esophageal, stomach and prostate cancers. Extensive studies from laboratory and animal models have revealed that garlic has a wide range of biological activities, and garlic organosulfur compounds (OSCs) are responsible for the biological activities. However, the presence and potency of garlic OSCs vary with respect to the mode of garlic preparation and extraction. Cooked or processed garlic products showed different kinds of garlic OSCs, some of which are highly unstable and instantly decomposed. These facts, possibly gave paradoxical results on the garlic effects. In this review, we first summarized the biotransformation processes of garlic alliin into different garlic OSCs as well as the garlic OSCs compositions from different garlic preparations. Next, we reviewed the chemopreventive functions and molecular mechanisms focusing on the anti-inflammation, antioxidation, anti-diabetes and anticancer activity behind different garlic OSCs.

  6. SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    C.J. Fernado

    1998-09-17

    The purpose of this document is to develop preliminary high-level functional and physical control system architectures for the proposed subsurface repository at Yucca Mountain. This document outlines overall control system concepts that encompass and integrate the many diverse systems being considered for use within the subsurface repository. This document presents integrated design concepts for monitoring and controlling the diverse set of subsurface operations. The subsurface repository design will be composed of a series of diverse systems that will be integrated to accomplish a set of overall functions and objectives. The subsurface repository contains several Instrumentation and Control (I&C) related systems including: waste emplacement systems, ventilation systems, communication systems, radiation monitoring systems, rail transportation systems, ground control monitoring systems, utility monitoring systems (electrical, lighting, water, compressed air, etc.), fire detection and protection systems, retrieval systems, and performance confirmation systems. Each of these systems involve some level of I&C and will typically be integrated over a data communication network. The subsurface I&C systems will also integrate with multiple surface-based site-wide systems such as emergency response, health physics, security and safeguards, communications, utilities and others. The scope and primary objectives of this analysis are to: (1) Identify preliminary system level functions and interface needs (Presented in the functional diagrams in Section 7.2). (2) Examine the overall system complexity and determine how and on what levels these control systems will be controlled and integrated (Presented in Section 7.2). (3) Develop a preliminary subsurface facility-wide design for an overall control system architecture, and depict this design by a series of control system functional block diagrams (Presented in Section 7.2). (4) Develop a series of physical architectures that

  7. CANCER CHEMOPREVENTIVE ACTIVITIES OF S-3-1,A SYNTHETIC DERIVATIVE OF DANSHINONE

    Institute of Scientific and Technical Information of China (English)

    XIAO-GUANG CHEN; YAN LI; CHUN-HONG YAN; LIAN-NIANG LI; RUI HAN

    2001-01-01

    Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[a]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[α]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promo tion agents through reversing the biochemical alterations induced by carcinogen during carcino genesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1inhibited the benzo[a]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts.At 10-40 mg/kg, S-3-1 was found to inhibit the development of DM BA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.

  8. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

    Directory of Open Access Journals (Sweden)

    Murthy N

    2009-01-01

    Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

  9. Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

    Institute of Scientific and Technical Information of China (English)

    Richard Jaszewski; Adhip PN Majumdar; Sabeena Misra; Martin Tobi; Nadeem Ullah; Jo Ann Naumoff; Omer Kucuk; Edi Levi; Bradley N Axelrod; Bhaumik B Patel

    2008-01-01

    AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas,the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps.METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years.RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation.CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.

  10. jPOSTrepo: an international standard data repository for proteomes

    Science.gov (United States)

    Okuda, Shujiro; Watanabe, Yu; Moriya, Yuki; Kawano, Shin; Yamamoto, Tadashi; Matsumoto, Masaki; Takami, Tomoyo; Kobayashi, Daiki; Araki, Norie; Yoshizawa, Akiyasu C.; Tabata, Tsuyoshi; Sugiyama, Naoyuki; Goto, Susumu; Ishihama, Yasushi

    2017-01-01

    Major advancements have recently been made in mass spectrometry-based proteomics, yielding an increasing number of datasets from various proteomics projects worldwide. In order to facilitate the sharing and reuse of promising datasets, it is important to construct appropriate, high-quality public data repositories. jPOSTrepo (https://repository.jpostdb.org/) has successfully implemented several unique features, including high-speed file uploading, flexible file management and easy-to-use interfaces. This repository has been launched as a public repository containing various proteomic datasets and is available for researchers worldwide. In addition, our repository has joined the ProteomeXchange consortium, which includes the most popular public repositories such as PRIDE in Europe for MS/MS datasets and PASSEL for SRM datasets in the USA. Later MassIVE was introduced in the USA and accepted into the ProteomeXchange, as was our repository in July 2016, providing important datasets from Asia/Oceania. Accordingly, this repository thus contributes to a global alliance to share and store all datasets from a wide variety of proteomics experiments. Thus, the repository is expected to become a major repository, particularly for data collected in the Asia/Oceania region. PMID:27899654

  11. Chemopreventive potential of Triphala (a composite Indian drug) on Benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system

    Energy Technology Data Exchange (ETDEWEB)

    Deep, G.; Dhirman, M.; Rao, A.R.; Kale, R.K. [Jawaharlan Nehru Univ., New Delhi (India). Radiation and Cancer Biology Laboratory

    2005-12-15

    The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27{+-}1.16 in the B(a)P treated control group, whereas it reduced to 3.00{+-}0.82 (p<0.005) by 2.5% dose and 2.33 +/- 1.03 (p<0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17{+-}0.75 (p<0.001) and 2.00{+-}0.71 (p<0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential.

  12. Chemopreventive effects of diverse dietary phytochemicals against DMBA-induced hamster buccal pouch carcinogenesis via the induction of Nrf2-mediated cytoprotective antioxidant, detoxification, and DNA repair enzymes.

    Science.gov (United States)

    Kavitha, K; Thiyagarajan, P; Rathna Nandhini, J; Mishra, Rajakishore; Nagini, S

    2013-08-01

    Identifying agents that activate nuclear factor erythroid-2 related factor-2 (Nrf2), a key regulator of various cytoprotective antioxidant, and detoxifying enzymes has evolved as a promising strategy for cancer chemoprevention. In the present study, we investigated the effect of dietary supplementation of structurally diverse phytochemicals- astaxanthin, blueberry, chlorophyllin, ellagic acid, and theaphenon-E on Nrf2 signaling, and xenobiotic-metabolizing and antioxidant enzymes in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model. We observed that these phytochemicals induce nuclear accumulation of Nrf2 while downregulating its negative regulator, Keap-1. This was associated with reduced expression of CYP1A1 and CYP1B1, the cytochrome P450 isoforms involved in the activation of DMBA, and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine coupled with upregulation of the phase II detoxification enzymes glutathione S-transferases and NAD(P)H:quinone oxidoreductase 1 and the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. In addition, these dietary phytochemicals also enhanced the DNA repair enzymes 8-oxoguanine glycosylase 1 (OGG1), xeroderma pigmentosum D (XPD), xeroderma pigmentosum G (XPG), and x-ray repair cross complementing group 1 (XRCC1). Our data provide substantial evidence that the dietary phytochemicals inhibit the development of HBP carcinomas through the activation of Nrf2/Keap-1 signaling and by upregulating cytoprotective enzymes. The extent of the chemopreventive effects of the phytochemicals was in the order: chlorophyllin > blueberry > ellagic acid > astaxanthin > theaphenon-E. Thus these dietary phytochemicals that function as potent activators of Nrf2 and its orchestrated response are novel candidates for cancer chemoprevention.

  13. Role of alpha class glutathione transferases (GSTs) in chemoprevention: GSTA1 and A4 overexpressing human leukemia (HL60) cells resist sulforaphane and curcumin induced toxicity.

    Science.gov (United States)

    Sharma, Rajendra; Ellis, Bryan; Sharma, Abha

    2011-04-01

    Alpha-class glutathione transferases (α-GSTs) have been shown to protect cells from the harmful effects of reactive oxygen species (ROS) induced lipid peroxidation (LPO) during oxidative stress caused by various physico-chemical agents. While GSTA1-1/A2-2 isozymes exhibit high activity towards lipid and fatty acid hydroperoxides through their selenium independent glutathione peroxidase (GPx) activity, the GSTA4-4 isozyme efficiently metabolizes the LPO product 4-hydroxynonenal (4-HNE) by conjugating it with glutathione (GSH). Because of the fact that ROS generated by the chemopreventive agents, sulforaphane (SFN) and curcumin (Cur), are implicated in the mechanisms of cancer cell killing, the present studies were designed to investigate the contribution of ROS induced LPO in the cytotoxic effects of these agents and the role of α-class GSTs in modulating their toxicity. Human erythroleukemic (HL60) cells were stably transfected with the cDNA encoding the hGSTA1-1 and mGsta4-4 isozymes. After analysing the expression and activities of the respective GST isozymes, the effects of SFN and Cur on the extent of LPO, cytotoxicity and apoptosis were compared in empty vector (VT), hGSTA1-1 and mGsta4-4 expressing HL60 cells. These studies demonstrate that when compared with SFN, Cur was relatively more cytotoxic to HL60 cells. The ectopic expression of hGSTA1-1 and mGsta4-4 isozymes provided resistance to SFN and Cur induced cytotoxicity and apoptosis through a significant suppression of LPO in these cells. Overall, the results suggest that the expression of α-class GSTs in cancer cells can modulate the therapeutic efficacy of chemopreventive agents.

  14. The French Geological Repository Project Cigeo - 12023

    Energy Technology Data Exchange (ETDEWEB)

    Harman, Alain; Labalette, Thibaud; Dupuis, Marie-Claude; Ouzounian, Gerald [ANDRA, Chatenay-Malabry (France)

    2012-07-01

    The French Agency for Radioactive Waste Management, ANDRA, was launched by law in 1991 to perform and develop the research programme for managing high level and intermediate level long-lived radioactive waste generated by the French nuclear fleet. After a 15-year intensive research programme, including the study of alternative solutions, an overall review and assessment of the results was organized, including a national public debate. As a result, the Parliament passed a Planning Act on radioactive waste management in 2006. Commissioning of a geological repository by 2025 was one of the most important decisions taken at that time. To reach this goal, a license application must be submitted and reviewed by the competent authorities by 2015. A detailed review and consultation process is, as well, defined in the Planning Act. Beside the legal framework the project needs to progress on two fronts. The first one is on siting. A significant milestone was reached in 2009 with the definition of a defined area to locate the underground repository facilities. This area was approved in March 2010 by the Government, after having collected the opinions and positions of all the interested parties, at both National and local levels. A new phase of dialogue with local players began to refine the implementation scenarios of surface facilities. The final site selection will be approved after a public debate planned for 2013. The second one is the industrial organization, planning and costing. The industrial project of this geological repository was called Cigeo (Centre Industriel de Stockage Geologique). Given the amount of work to be done to comply with the given time framework, a detailed organization with well-defined milestones must be set-up. Cigeo will be a specific nuclear facility, built and operated underground for over a hundred years. The consequence of this long duration is that the development of the repository facilities will take place in successive operational phases

  15. Russian Geologic Repository Technical Papers and Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jardine, L

    2002-02-18

    Lawrence Livermore National Laboratory (LLNL) has been actively and continuously engaged in Russian geologic disposal activities since 1995. The first joint US-Russian meeting on Disposition of Excess Weapons Plutonium was held in January 1995 at Los Alamos National Laboratory (LANL). The meeting resulted in the appointment of Dr. L. J. Jardine from LLNL and Dr. T. A. Gupalo from the All-Russian Research and Design Institute of Production Engineering (VNIPIPT) as the US-Russian Federation (RF) joint co-chairs for geologic disposal of plutonium-containing materials, respectively. The initial joint studies focused on the geologic disposal of plutonium-containing materials and immobilized plutonium waste forms. These studies started in 1995, and continue in 2002. The first joint work of LLNL and VNIPIPT was documented in the October 1996 Paris P8 Nuclear Experts Meeting [1]. In summary, LLNL has been actively and continuously involved in various ways since 1995 in developing and participating in the current Russian geologic disposal program activities near the Mayak and MCC K-26 sites. Figure 1 illustrates how these various LLNL activities have been integrated, coordinated, and focused on developing geologic disposal in Russia. The various LLNL contracts are shown in the figure with the specific LLNL contract number. Reference 13 provides a summary of the status in 2000 of the past Russian repository program activities for the K-26 and Mayak sites. Because of this unique continuous and direct participation in the RF geologic disposal program activities, LLNL has either obtained or generated numerous technical papers and reports documenting various aspects of the RF geologic repository activities for the two sites near the Minatom industrial sites at Mayak and K-26. As a result, LLNL decided to collect these unique documents into one referenceable set and generated this report. This report collects these technical papers, technical reports, plans, and proposals for

  16. Status of Proposed Repository for Latin-American Spent Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Ferrada, J.J.

    2004-10-04

    This report compiles preliminary information that supports the premise that a repository is needed in Latin America and analyzes the nuclear situation (mainly in Argentina and Brazil) in terms of nuclear capabilities, inventories, and regional spent-fuel repositories. The report is based on several sources and summarizes (1) the nuclear capabilities in Latin America and establishes the framework for the need of a permanent repository, (2) the International Atomic Energy Agency (IAEA) approach for a regional spent-fuel repository and describes the support that international institutions are lending to this issue, (3) the current situation in Argentina in order to analyze the Argentinean willingness to find a location for a deep geological repository, and (4) the issues involved in selecting a location for the repository and identifies a potential location. This report then draws conclusions based on an analysis of this information. The focus of this report is mainly on spent fuel and does not elaborate on other radiological waste sources.

  17. Selection of Corrosion Resistant Materials for Nuclear Waste Repositories

    Energy Technology Data Exchange (ETDEWEB)

    R.B. Rebak

    2006-08-28

    Several countries are considering geological repositories to dispose of nuclear waste. The environment of most of the currently considered repositories will be reducing in nature, except for the repository in the US, which is going to be oxidizing. For the reducing repositories, alloys such as carbon steel, stainless steels and titanium are being evaluated. For the repository in the US, some of the most corrosion resistant commercially available alloys are being investigated. This paper presents a summary of the behavior of the different materials under consideration for the repositories and the current understanding of the degradation modes of the proposed alloys in ground water environments from the point of view of general corrosion, localized corrosion and environmentally assisted cracking.

  18. Selection of Corrosion Resistant Materials for Nuclear Waste Repositories

    Energy Technology Data Exchange (ETDEWEB)

    Rebak, R B

    2006-06-01

    Several countries are considering geological repositories to dispose of nuclear waste. The environment of most of the currently considered repositories will be reducing in nature, except for the repository in the US, which is going to be oxidizing. For the reducing repositories alloys such as carbon steel, stainless steels and titanium are being evaluated. For the repository in the US, some of the most corrosion resistant commercially available alloys are being investigated. This paper presents a summary of the behavior of the different materials under consideration for the repositories and the current understanding of the degradation modes of the proposed alloys in ground water environments from the point of view of general corrosion, localized corrosion and environmentally assisted cracking.

  19. Monitored Geologic Repository Project Description Document

    Energy Technology Data Exchange (ETDEWEB)

    P. M. Curry

    2001-01-30

    The primary objective of the Monitored Geologic Repository Project Description Document (PDD) is to allocate the functions, requirements, and assumptions to the systems at Level 5 of the Civilian Radioactive Waste Management System (CRWMS) architecture identified in Section 4. It provides traceability of the requirements to those contained in Section 3 of the ''Monitored Geologic Repository Requirements Document'' (MGR RD) (YMP 2000a) and other higher-level requirements documents. In addition, the PDD allocates design related assumptions to work products of non-design organizations. The document provides Monitored Geologic Repository (MGR) technical requirements in support of design and performance assessment in preparing for the Site Recommendation (SR) and License Application (LA) milestones. The technical requirements documented in the PDD are to be captured in the System Description Documents (SDDs) which address each of the systems at Level 5 of the CRWMS architecture. The design engineers obtain the technical requirements from the SDDs and by reference from the SDDs to the PDD. The design organizations and other organizations will obtain design related assumptions directly from the PDD. These organizations may establish additional assumptions for their individual activities, but such assumptions are not to conflict with the assumptions in the PDD. The PDD will serve as the primary link between the technical requirements captured in the SDDs and the design requirements captured in US Department of Energy (DOE) documents. The approved PDD is placed under Level 3 baseline control by the CRWMS Management and Operating Contractor (M and O) and the following portions of the PDD constitute the Technical Design Baseline for the MGR: the design characteristics listed in Table 1-1, the MGR Architecture (Section 4.1), the Technical Requirements (Section 5), and the Controlled Project Assumptions (Section 6).

  20. Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

    2013-01-01

    Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model....

  1. Un repository semantico per la Special Education

    Directory of Open Access Journals (Sweden)

    Vincenza Benigno

    2013-08-01

    Full Text Available La ricerca nella mole sconfinata di informazioni e risorse disponibili in rete rappresenta sicuramente un problema che oggi viene riconosciuto come sovraccarico informativo . Una possibile soluzione arriva dalle tecnologie di knowledge e dalla semantica. Nell’ambito del presente contributo verrà descritta la metodologia per lo sviluppo dello user modelling finalizzato a descrivere il profilo e il contesto di riferimento degli utenti nell’utilizzo di un repository semantico sviluppato per la Special Education, il Knowledge Hub (KH. In relazione al KH verranno descritte le principali funzionalità e le tipologie di risorse presenti.

  2. Digital Archive Policies and Trusted Digital Repositories

    Directory of Open Access Journals (Sweden)

    MacKenzie Smith

    2007-07-01

    Full Text Available The MIT Libraries, the San Diego Supercomputer Center, and the University of California San Diego Libraries are conducting the PLEDGE Project to determine the set of policies that affect operational digital preservation archives and to develop standardized means of recording and enforcing them using rules engines. This has the potential to allow for automated assessment of “trustworthiness” of digital preservation archives. We are also evaluating the completeness of other efforts to define policies for digital preservation such as the RLG/NARA Trusted Digital Repository checklist and the PREMIS metadata schema. We present our results to date.

  3. Microbial processes in a clay repository

    Energy Technology Data Exchange (ETDEWEB)

    Canniere, Pierre de [Federal Agency of Nuclear Control (FANC), Brussels (Belgium); Meleshyn, Artur [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Braunschweig (Germany)

    2013-07-01

    The safety of a deep geologic repository (DGR) for nuclear waste must be ensured for geological times exceeding human imagination taking into account large uncertainties. The long-term effects of complex biogeochemical processes potentially affecting the integrity and the long-term safety of engineered barriers might still be unknown. The aim of this presentation is to give a general overview of some microbial processes which have contributed to shape the Earth since probably billions of years and whose unexpected consequences for nuclear waste disposal should be appropriately tackled. (orig.)

  4. DAR: A Modern Institutional Repository with a Scalability Twist

    OpenAIRE

    Mikhail, Youssef; Adly, Noha; Nagi, Magdy

    2012-01-01

    The Digital Assets Repository (DAR) is an Institutional Repository developed at the Bibliotheca Alexandrina to manage the full lifecycle of a digital asset: its creation and ingestion, its metadata management, storage and archival in addition to the necessary mechanisms for publishing and dissemination. DAR was designed with a focus on integrating DAR with different sources of digital objects and metadata in addition to integration with applications built on top of the repository. As a modern...

  5. Oral chemoprevention with acetyl salicylic Acid, vitamin d and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, J; Rosenberg, J

    2013-01-01

    , and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet...

  6. Is There a Role for Research Students in an Institutional Repository? Some Repository Managers' Views

    Science.gov (United States)

    Pickton, Margaret; McKnight, Cliff

    2007-01-01

    Although a number of studies have investigated the attitudes of published academic authors with respect to open access (OA) publishing and institutional repositories (IRs), none have considered the views of other institutional stakeholders. Research students, in particular, are a group that could make a major contribution to an IR, both currently…

  7. National Geoscience Data Repository System, Phase III: Implementation and Operation of the Repository

    Energy Technology Data Exchange (ETDEWEB)

    American Geological Institute

    1999-11-09

    The NGDRS steering committee met at Unocal's offices on October 1, 1998 in Sugar Land, Texas to review and discuss issues of data transfer and the continued development of the Stapleton prospect for establishment of a national core repository. Company representatives reaffirmed their commitment to donate geoscience data to the NGDRS once appropriate facilities are available.

  8. New content in digital repositories the changing research landscape

    CERN Document Server

    Simons, Natasha

    2013-01-01

    Research institutions are under pressure to make their outputs more accessible in order to meet funding requirements and policy guidelines. Libraries have traditionally played an important role by exposing research output through a predominantly institution-based digital repository, with an emphasis on storing published works. New publishing paradigms are emerging that include research data, huge volumes of which are being generated globally. Repositories are the natural home for managing, storing and describing institutional research content. New Content in Digital Repositories explores the diversity of content types being stored in digital repositories with a focus on research data, creative works, and the interesting challenges they pose.

  9. Digital Repositories An investigation of best practices for content recruitment to academic digital repositories and the conditions for their livelihood

    CERN Document Server

    Hagen, Reidun Anette

    2009-01-01

    A digital repository is a web accessible database, aimed at preserving the research material of an institution or scientific community. A digital repository serves as a tool for dissemination of research material and can increase the impact of the research by making it freely accessible. Digital repositories are often mentioned as a possible aid in relation to the Open Access debate; how research material should be freely accessible to anyone, anywhere at any time. However, for a digital repository to fully unleash its potential as a crucial component of Open Access, it is reliant on the ability to successfully collect and organize content. To a large extent this involves initiating self-archiving of research material by scientists throughout the academic world. This is not a trivial task, and many current repositories are inadequate in this respect, remaining empty, unvisited shelves. This thesis explores best practices for content recruitment to digital repositories, through the review of literature, and an...

  10. 绿茶对前列腺癌的化学预防作用%Green tea in chemoprevention of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    贾晓龙; 秦杰

    2008-01-01

    绿茶是许多国家和地区的重要饮料之一,近年来不断有体外和动物体内实验表明绿茶可以诱导前列腺癌细胞凋亡、抑制前列腺癌浸润及转移,流行病学调查及临床试验也发现绿茶对前列腺癌具有预防作用,可减少高分级前列腺上皮内瘤发展成为前列腺癌的概率,将有可能成为良好的前列腺癌化学预防物质.%Green tea as a main beverage is consumed worldwide. In the last few years, .green tea has been shown to induce apoptosis and to inhibit the infiltration and metastasis of prostate cancer by in vitro and in vivo experiments. Epidemiologic investigations and clinical trials also have demonstrated the chemopreventive role of green tea in prostate cancer, such as reducing the possibility of carcinogenesis of high-grade prostatic in-traepithelial neoplasia, and is hopeful to be applied as chemopreventive agent of prostate cancer in the future.

  11. Learning object repositories as knowledge management systems

    Directory of Open Access Journals (Sweden)

    Demetrios G. Sampson

    2013-06-01

    Full Text Available Over the past years, a number of international initiatives that recognize the importance of sharing and reusing digital educational resources among educational communities through the use of Learning Object Repositories (LORs have emerged. Typically, these initiatives focus on collecting digital educational resources that are offered by their creators for open access and potential reuse. Nevertheless, most of the existing LORs are designed more as digital repositories, rather than as Knowledge Management Systems (KMS. By exploiting KMSs functionalities in LORs would bare the potential to support the organization and sharing of educational communities’ explicit knowledge (depicted in digital educational resources constructed by teachers and/or instructional designers and tacit knowledge (depicted in teachers’ and students’ experiences and interactions of using digital educational resources available in LORs. Within this context, in this paper we study the design and the implementation of fourteen operating LORs from the KMSs’ perspective, so as to identify additional functionalities that can support the management of educational communities’ explicit and tacit knowledge. Thus, we propose a list of essential LORs’ functionalities, which aim to facilitate the organization and sharing of educational communities’ knowledge. Finally, we present the added value of these functionalities by identifying their importance towards addressing the current demands of web-facilitated educational communities, as well as the knowledge management activities that they execute.

  12. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

    Science.gov (United States)

    Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V.; Schultz, David J.; Gupta, Ramesh C.

    2017-01-01

    Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in control

  13. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

    Directory of Open Access Journals (Sweden)

    Farrukh Aqil

    2017-02-01

    Full Text Available Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish rat model. Female ACI rats were given either control diet (AIN 93M or diet supplemented with 7.5% (w/w of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα. The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92

  14. 非甾体类抗炎药与消化道肿瘤的化学预防%Non-steroidal Anti-inflammatory Drugs and Chemoprevention of Digestive Cancer

    Institute of Scientific and Technical Information of China (English)

    魏文强; 乔友林

    2001-01-01

    Recent epidemiology and laboratory studies indicate that regular taking of aspirin and other non-steroidal anti-inflammatory drugs(NSAIDs) may reduce the risk of colorectal, esophageal, stomach and pancreatic cancers and other digestive cancers. Thus, aspirin and other NSAIDs may be an effective chemoprevention agent for digestive cancers. On the other hand, this protection effort may be benefitial to the course of the intervention, regression and prevention of cancer lesions. The possible mechanism of NSAIDs chemoprevention may be: (1)reducing the synthesis of prostaglandin(PG) and inhibiting cyclo-oxygenase(COX) activity; (2) inducing apoptosis in epithelial cells of the gastro-intestinal origin; (3)obstructing signaling transduction pathways of COX and PG. Now, chemoprevention of NSAIDs has become focus of research on cancer secondary prevention, as its protective effects of chemoprevention of digesrive cancer have been determined. NSAIDs, especially selective COX-2 inhibitor may be a novel useful chemoprevention agents for digestive cancer and their precursor lesions in future.%近年来,流行病学及实验室研究表明,长期使用阿斯匹林或其它非甾体类抗炎药(NSAIDs),可降低结、直肠癌、食管癌、胃癌、胰腺癌等消化道肿瘤的发病危险性,提示NSAIDs可能对消化道肿瘤具有一定的化学预防作用。同时,这一保护作用也很有可能在肿瘤的前期病变过程中发挥有益的阻断、逆转或预防作用。NSAIDs化学预防作用的可能机制:(1)抑制前列腺素(PG)合成和细胞环氧化酶(COX)活性;(2)诱导胃肠道来源的上皮细胞凋亡;(3)引起PG和COX调节通路的障碍。目前,NSAIDs的化学预防作用已经成为肿瘤二级预防领域的研究热点并已基本肯定了它在消化道肿瘤预防中的作用。NSAIDs,尤其是特异性环氧化酶-2抑制剂,有望成为肿瘤以及癌前病变新的化学预防的药物。

  15. Science Is the First Step to Siting Nuclear Waste Repositories

    Science.gov (United States)

    Neuzil, C. E.

    2014-02-01

    As Shaw [2014] notes, U.S. research on shale as a repository host was halted before expending anything close to the effort devoted to studying crystalline rock, salt, and—most notably—tuff at Yucca Mountain. The new political reality regarding Yucca Mountain may allow reconsideration of the decision to abandon research on shale as a repository host.

  16. Structure, Features, and Faculty Content in ARL Member Repositories

    Science.gov (United States)

    Mercer, Holly; Koenig, Jay; McGeachin, Robert B.; Tucker, Sandra L.

    2011-01-01

    Questions about the optimal way to present repository content to authors, submitters, and end-users, prompted this study. The authors examined, through an observation and a survey, the institutional repositories of peer institutions in the ARL for good practices related to the presentation and organization of faculty-authored institutional…

  17. Collaboration Nation: The Building of the Welsh Repository Network

    Science.gov (United States)

    Knowles, Jacqueline

    2010-01-01

    Purpose: The purpose of this paper is to disseminate information about the Welsh Repository Network (WRN), innovative work being undertaken to build an integrated network of institutional digital repositories. A collaborative approach, in particular through the provision of centralised technical and organisational support, has demonstrated…

  18. Exploring the Coming Repositories of Reproducible Experiments: Challenges and Opportunities

    DEFF Research Database (Denmark)

    Freire, Juliana; Bonnet, Philippe; Shasha, Dennis

    2011-01-01

    Computational reproducibility efforts in many communities will soon give rise to validated software and data repositories of high quality. A scientist in a field may want to query the components of such repositories to build new software workflows, perhaps after adding the scientist’s own algorithm...

  19. 10 CFR 51.67 - Environmental information concerning geologic repositories.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Environmental information concerning geologic repositories... information concerning geologic repositories. (a) In lieu of an environmental report, the Department of Energy... if it makes a substantial change in its proposed action that is relevant to environmental concerns...

  20. 15 CFR 1180.10 - NTIS permanent repository.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false NTIS permanent repository. 1180.10... ENGINEERING INFORMATION TO THE NATIONAL TECHNICAL INFORMATION SERVICE § 1180.10 NTIS permanent repository. A product, or category of product, will normally be accepted and maintained as part of NTIS'...

  1. Evolution of a Digital Repository: One Institution's Experience

    Science.gov (United States)

    Owen, Terry M.

    2011-01-01

    In this article, the development of a digital repository is examined, specifically how the focus on acquiring content for the repository has transitioned from faculty-published research to include the gray literature produced by the research centers on campus, including unpublished technical reports and undergraduate research from honors programs.…

  2. Digital Preservation in the Context of Institutional Repositories

    Science.gov (United States)

    Hockx-Yu, Helen

    2006-01-01

    Purpose: To discuss the issues and challenges of digital preservation facing institutional repositories and to illustrate the Joint Information Systems Committee's (JISC) view on institutional repositories and its key initiatives in helping UK institutions address these issues. Design/methodology/approach: A combination of published work and JISC…

  3. Neural network-based retrieval from software reuse repositories

    Science.gov (United States)

    Eichmann, David A.; Srinivas, Kankanahalli

    1992-01-01

    A significant hurdle confronts the software reuser attempting to select candidate components from a software repository - discriminating between those components without resorting to inspection of the implementation(s). We outline an approach to this problem based upon neural networks which avoids requiring the repository administrators to define a conceptual closeness graph for the classification vocabulary.

  4. Current developments in container design testing for the Konrad repository

    Energy Technology Data Exchange (ETDEWEB)

    Voelzke, Holger; Nieslony, Gregor; Noack, Volker; Hagenow, Peter; Kovacs, Oliver [Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin (Germany)

    2012-05-15

    In 2002, the Konrad repository was licensed as a repository for radioactive waste generating no heat. That permit subsequently became the object of litigation and was confirmed by a court of last resort as late as in 2007. The Federal Office of Radiation Protection (BfS) then started planning and converting the former iron ore mine into a repository. The licensed repository volume is 303,000 m{sup 3} based on estimates of expected waste arisings. The mine proper would offer a much larger volume. However, cask emplacement can be started only after completion of the repository which, according to the present status, will not be before the end of this decade. Nevertheless, there is great interest even now in conditioning and packaging for repository storage of the radioactive waste planned for Konrad, which also requires casks type tested by the Federal Institute of Materials Testing (BAM) and approved by the BfS. The key items in the license for the repository are comprehensive requirements to be met by waste forms and casks. As far as continuous revision of repository requirements and consideration of materials hazardous to water are concerned, it is assumed that the key requirements applying to type tests of casks with respect to waste forms and casks will be affected by this either not at all or only very slightly. (orig.)

  5. Digital Libraries and Repositories in India: An Evaluative Study

    Science.gov (United States)

    Mittal, Rekha; Mahesh, G.

    2008-01-01

    Purpose: The purpose of this research is to identify and evaluate the collections within digital libraries and repositories in India available in the public domain. Design/methodology/approach: The digital libraries and repositories were identified through a study of the literature, as well as internet searching and browsing. The resulting digital…

  6. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention

    Science.gov (United States)

    Johnson, Jeremy J.; Syed, Deeba N.; Suh, Yewseok; Heren, Chenelle R.; Saleem, Mohammad; Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Emerging data is suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of non-toxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling we found carnosol, a dietary diterpene fits within the ligand binding domain of both AR and ER-α. Using a TR-FRET assay we found that carnosol interacts with both AR and ER-α and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20–40 µM) showed decreased protein expression of AR and ER-α. Oral administration of carnosol at 30 mg/kg five days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (p = 0.028) and was associated with a decrease in serum PSA by 26% (p=0.0042). These properties make carnosol unique to any known anti-androgen or anti-estrogen investigated so far for the simultaneous disruption of AR and ER-α. We suggest that carnosol may be developed or chemically modified through more rigorous structure activity relationship studies for a new class of investigational agents - a dual AR/ER modulator. PMID:20736335

  7. Repositories in an institutional context : Technical discussion Group 4

    CERN Document Server

    CERN. Geneva

    2007-01-01

    Repositories are starting to take their place within an institution¹s infrastructure, sitting alongside portals, course management systems, virtual research environments and others. But in considering how a repository can best serve an institution it is important to consider how this technology will integrate with existing systems, so that it doesn¹t become a standalone white elephant that is a nuisance to use. This breakout will consider the technical ways in which repositories can be presented as a system that is easy to use and interact with, from the searcher¹s, depositor¹s and administrator¹s perspectives. It will look at potential interaction through other institutional environments and seek to identify ways in which repositories can become a more integral part of the technical landscape. Bring along your examples of how repositories are being technically embedded within institutions to help share experience and ideas.

  8. [The subject repositories of strategy of the Open Access initiative].

    Science.gov (United States)

    Soares Guimarães, M C; da Silva, C H; Horsth Noronha, I

    2012-11-01

    The subject repositories are defined as a set of digital objects resulting from the research related to a specific disciplinary field and occupy a still restricted space in the discussion agenda of the Free Access Movement when compared to amplitude reached in the discussion of Institutional Repositories. Although the Subject Repository comes to prominence in the field, especially for the success of initiatives such as the arXiv, PubMed and E-prints, the literature on the subject is recognized as very limited. Despite its roots in the Library and Information Science, and focus on the management of disciplinary collections (subject area literature), there is little information available about the development and management of subject repositories. The following text seeks to make a brief summary on the topic as a way to present the potential to develop subject repositories in order to strengthen the initiative of open access.

  9. Design and production of the KBS-3 repository

    Energy Technology Data Exchange (ETDEWEB)

    Moren, Lena

    2010-12-15

    The report contains the common basis for a set of Production reports, presenting how the KBS-3 repository is designed, produced and inspected. The set of reports is included in the safety report for the KBS-3 repository and repository facility. The report presents the role of the Production reports within the safety report and their common purposes and objectives. An important part of the report is to present the background and sources to the principles to be applied in the design, the functions of the KBS-3 repository and the barrier functions the engineered barriers and rock. Further, the methodology to substantiate detailed design premises for the engineered barriers, underground openings and other parts of the KBS-3 repository is presented. The report also gives an overview of the KBS-3 system and its facilities and the production lines for the spent fuel, the engineered barriers and underground openings. Finally, an introduction to quality management, safety classification and their application is given

  10. Space Telecommunications Radio System (STRS) Application Repository Design and Analysis

    Science.gov (United States)

    Handler, Louis M.

    2013-01-01

    The Space Telecommunications Radio System (STRS) Application Repository Design and Analysis document describes the STRS application repository for software-defined radio (SDR) applications intended to be compliant to the STRS Architecture Standard. The document provides information about the submission of artifacts to the STRS application repository, to provide information to the potential users of that information, and for the systems engineer to understand the requirements, concepts, and approach to the STRS application repository. The STRS application repository is intended to capture knowledge, documents, and other artifacts for each waveform application or other application outside of its project so that when the project ends, the knowledge is retained. The document describes the transmission of technology from mission to mission capturing lessons learned that are used for continuous improvement across projects and supporting NASA Procedural Requirements (NPRs) for performing software engineering projects and NASAs release process.

  11. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  12. Chemoprevention of intestinal tumorigenesis by nabumetone: induction of apoptosis and Bcl-2 downregulation.

    Science.gov (United States)

    Roy, H K; Karoski, W J; Ratashak, A; Smyrk, T C

    2001-05-18

    Treatment of MIN mice with the nonsteroidal anti-inflammatory drug, nabumetone, resulted in a dose-dependent suppression of intestinal tumorigenesis. In both the uninvolved MIN mouse colonic epithelium and HT-29 colon cancer cells, nabumetone downregulated the anti-apoptotic protein, Bcl-2, with concomitant induction of apoptosis, suggesting a potential mechanism for colon cancer chemoprevention.

  13. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2007-01-01

    Resveratrol, a naturally occurring compound of various fruits such as grapes, is thought to possess chemopreventive properties. The levels of resveratrol in grapes and grape products including wine, varies from region to region and from one year to another. This paper reviews the resveratrol...

  14. Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis.

    Science.gov (United States)

    Zhang, Ling; Ren, Xiaoyang; Alt, Eckhard; Bai, Xiaowen; Huang, Shaoyi; Xu, Zhengming; Lynch, Patrick M; Moyer, Mary P; Wen, Xian-Feng; Wu, Xiangwei

    2010-04-15

    Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.

  15. Effect of a vegan diet on biomarkers of chemoprevention in females

    NARCIS (Netherlands)

    Verhagen, H.; Rauma, A.L.; Törrönen, R.; Vogel, N. de; Bruijntjes-Rozier, G.C.D.M.; Dreve, M.A.; Bogaards, J.J.P.; Mykkänen, H.

    1996-01-01

    1. In order to study the potential beneficial effects of a vegan diet, a cross-sectional study was performed and several biomarkers of chemoprevention were measured in a population of female 'living food' eaters ('vegans'; n = 20) vs matched omnivorous controls (n = 20). 2. White blood cells obtaine

  16. A Study of Scala Repositories on Github

    Directory of Open Access Journals (Sweden)

    Ron Coleman

    2014-08-01

    Full Text Available Functional programming appears to be enjoying a renaissance of interest for developing practical, “real-world” applications. Proponents have long maintained that the functional style is a better way to modularize programs and reduce complexity. What is new in this paper is we test this claim by studying the complexity of open source codes written in Scala, a modern language that unifies functional and object programming. We downloaded from GitHub, Inc., a portfolio of mostly “trending” Scala repositories that included the Scala compiler and standard library, much of them written in Scala; the Twitter, Inc., server and its support libraries; and many other repositories, several of them production-oriented and commercially inspired. In total we investigated approximately 22,000 source files with 2 millions lines of code and 223,000 methods written by hundreds of programmers. To analyze these sources, we developed a novel compiler kit that measures lines of code and adaptively learns to estimate the cyclomatic complexity of functional-object codes. The data show, first, lines of code and cyclomatic complexity are positively correlated as we expected but only weakly which we did not expect with Kendall’s t=0.258–0.274. Second, 75% of the Scala methods are straight-line, that is, they have the lowest possible cyclomatic complexity. Third, nearly 70% of methods have three or fewer lines. Fourth, the distributions of lines of code and cyclomatic complexity are both non-Gaussian (P<0.01, which is as surprising as it is interesting. These data may offer new insights into software complexity and the large-scale structure of applications including but not necessarily limited to Scala.

  17. The PBase Scientific Workflow Provenance Repository

    Directory of Open Access Journals (Sweden)

    Víctor Cuevas-Vicenttín

    2014-10-01

    Full Text Available Scientific workflows and their supporting systems are becoming increasingly popular for compute-intensive and data-intensive scientific experiments. The advantages scientific workflows offer include rapid and easy workflow design, software and data reuse, scalable execution, sharing and collaboration, and other advantages that altogether facilitate “reproducible science”. In this context, provenance – information about the origin, context, derivation, ownership, or history of some artifact – plays a key role, since scientists are interested in examining and auditing the results of scientific experiments. However, in order to perform such analyses on scientific results as part of extended research collaborations, an adequate environment and tools are required. Concretely, the need arises for a repository that will facilitate the sharing of scientific workflows and their associated execution traces in an interoperable manner, also enabling querying and visualization. Furthermore, such functionality should be supported while taking performance and scalability into account. With this purpose in mind, we introduce PBase: a scientific workflow provenance repository implementing the ProvONE proposed standard, which extends the emerging W3C PROV standard for provenance data with workflow specific concepts. PBase is built on the Neo4j graph database, thus offering capabilities such as declarative and efficient querying. Our experiences demonstrate the power gained by supporting various types of queries for provenance data. In addition, PBase is equipped with a user friendly interface tailored for the visualization of scientific workflow provenance data, making the specification of queries and the interpretation of their results easier and more effective.

  18. The Open Data Repository's Data Publisher

    Science.gov (United States)

    Stone, N.; Lafuente, B.; Downs, R. T.; Bristow, T.; Blake, D. F.; Fonda, M.; Pires, A.

    2015-12-01

    Data management and data publication are becoming increasingly important components of research workflows. The complexity of managing data, publishing data online, and archiving data has not decreased significantly even as computing access and power has greatly increased. The Open Data Repository's Data Publisher software (http://www.opendatarepository.org) strives to make data archiving, management, and publication a standard part of a researcher's workflow using simple, web-based tools and commodity server hardware. The publication engine allows for uploading, searching, and display of data with graphing capabilities and downloadable files. Access is controlled through a robust permissions system that can control publication at the field level and can be granted to the general public or protected so that only registered users at various permission levels receive access. Data Publisher also allows researchers to subscribe to meta-data standards through a plugin system, embargo data publication at their discretion, and collaborate with other researchers through various levels of data sharing. As the software matures, semantic data standards will be implemented to facilitate machine reading of data and each database will provide a REST application programming interface for programmatic access. Additionally, a citation system will allow snapshots of any data set to be archived and cited for publication while the data itself can remain living and continuously evolve beyond the snapshot date. The software runs on a traditional LAMP (Linux, Apache, MySQL, PHP) server and is available on GitHub (http://github.com/opendatarepository) under a GPLv2 open source license. The goal of the Open Data Repository is to lower the cost and training barrier to entry so that any researcher can easily publish their data and ensure it is archived for posterity. We gratefully acknowledge the support for this study by the Science-Enabling Research Activity (SERA), and NASA NNX11AP82A

  19. The Open Data Repositorys Data Publisher

    Science.gov (United States)

    Stone, N.; Lafuente, B.; Downs, R. T.; Blake, D.; Bristow, T.; Fonda, M.; Pires, A.

    2015-01-01

    Data management and data publication are becoming increasingly important components of researcher's workflows. The complexity of managing data, publishing data online, and archiving data has not decreased significantly even as computing access and power has greatly increased. The Open Data Repository's Data Publisher software strives to make data archiving, management, and publication a standard part of a researcher's workflow using simple, web-based tools and commodity server hardware. The publication engine allows for uploading, searching, and display of data with graphing capabilities and downloadable files. Access is controlled through a robust permissions system that can control publication at the field level and can be granted to the general public or protected so that only registered users at various permission levels receive access. Data Publisher also allows researchers to subscribe to meta-data standards through a plugin system, embargo data publication at their discretion, and collaborate with other researchers through various levels of data sharing. As the software matures, semantic data standards will be implemented to facilitate machine reading of data and each database will provide a REST application programming interface for programmatic access. Additionally, a citation system will allow snapshots of any data set to be archived and cited for publication while the data itself can remain living and continuously evolve beyond the snapshot date. The software runs on a traditional LAMP (Linux, Apache, MySQL, PHP) server and is available on GitHub (http://github.com/opendatarepository) under a GPLv2 open source license. The goal of the Open Data Repository is to lower the cost and training barrier to entry so that any researcher can easily publish their data and ensure it is archived for posterity.

  20. Monitored Geologic Repository Project Description Document

    Energy Technology Data Exchange (ETDEWEB)

    P. Curry

    2001-06-26

    The primary objective of the Monitored Geologic Repository Project Description Document (PDD) is to allocate the functions, requirements, and assumptions to the systems at Level 5 of the Civilian Radioactive Waste Management System (CRWMS) architecture identified in Section 4. It provides traceability of the requirements to those contained in Section 3 of the Yucca Mountain Site Characterization Project Requirements Document (YMP RD) (YMP 2001a) and other higher-level requirements documents. In addition, the PDD allocates design related assumptions to work products of non-design organizations. The document provides Monitored Geologic Repository (MGR) technical requirements in support of design and performance assessment in preparing for the Site Recommendation (SR) and License Application (LA) milestones. The technical requirements documented in the PDD are to be captured in the System Description Documents (SDDs) which address each of the systems at Level 5 of the CRWMS architecture. The design engineers obtain the technical requirements from the SDDs and by reference from the SDDs to the PDD. The design organizations and other organizations will obtain design related assumptions directly from the PDD. These organizations may establish additional assumptions for their individual activities, but such assumptions are not to conflict with the assumptions in the PDD. The PDD will serve as the primary link between the technical requirements captured in the SDDs and the design requirements captured in US Department of Energy (DOE) documents. The approved PDD is placed under Level 3 baseline control by the CRWMS Management and Operating Contractor (M&O) and the following portions of the PDD constitute the Technical Design Baseline for the MGR: the design characteristics listed in Table 1-1, the MGR Architecture (Section 4.1), the Technical Requirements (Section 5), and the Controlled Project Assumptions (Section 6).

  1. Repository surface design site layout analysis

    Energy Technology Data Exchange (ETDEWEB)

    Montalvo, H.R.

    1998-02-27

    The purpose of this analysis is to establish the arrangement of the Yucca Mountain Repository surface facilities and features near the North Portal. The analysis updates and expands the North Portal area site layout concept presented in the ACD, including changes to reflect the resizing of the Waste Handling Building (WHB), Waste Treatment Building (WTB), Carrier Preparation Building (CPB), and site parking areas; the addition of the Carrier Washdown Buildings (CWBs); the elimination of the Cask Maintenance Facility (CMF); and the development of a concept for site grading and flood control. The analysis also establishes the layout of the surface features (e.g., roads and utilities) that connect all the repository surface areas (North Portal Operations Area, South Portal Development Operations Area, Emplacement Shaft Surface Operations Area, and Development Shaft Surface Operations Area) and locates an area for a potential lag storage facility. Details of South Portal and shaft layouts will be covered in separate design analyses. The objective of this analysis is to provide a suitable level of design for the Viability Assessment (VA). The analysis was revised to incorporate additional material developed since the issuance of Revision 01. This material includes safeguards and security input, utility system input (size and location of fire water tanks and pump houses, potable water and sanitary sewage rates, size of wastewater evaporation pond, size and location of the utility building, size of the bulk fuel storage tank, and size and location of other exterior process equipment), main electrical substation information, redundancy of water supply and storage for the fire support system, and additional information on the storm water retention pond.

  2. The Research Library's Role in Digital Repository Services: Final Report of the ARL Digital Repository Issues Task Force

    Science.gov (United States)

    Association of Research Libraries, 2009

    2009-01-01

    Libraries are making diverse contributions to the development of many types of digital repositories, particularly those housing locally created digital content, including new digital objects or digitized versions of locally held works. In some instances, libraries are managing a repository and its related services entirely on their own, but often…

  3. Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention

    Science.gov (United States)

    Ziv, Elad; Tice, Jeffrey A.; Sprague, Brian; Vachon, Celine M.; Cummings, Steven R.; Kerlikowske, Karla

    2017-01-01

    Background Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. Methods We used the risk distribution among women ages 35–69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. Results We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women), ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women), ~90% of the benefit of testing all women would be derived. Conclusion SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention. PMID:28107349

  4. Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone.

    Science.gov (United States)

    Roy, H K; Karolski, W J; Ratashak, A

    2001-05-15

    Use of non-steroidal anti-inflammatory drugs (NSAIDs) for chemoprevention of colon cancer has been hindered by their potential gastro-intestinal toxicity. Nabumetone, which is approximately 10 to 36 times safer than conventional NSAIDs, was evaluated in 2 models of experimental colon carcinogenesis. In azoxymethane (AOM)-treated Fisher 344 rats, nabumetone caused dose-dependent inhibition of aberrant crypt foci (ACF), with 750 and 1,500 ppm resulting in 15% and 37% reductions, respectively (p nabumetone, with 900 ppm suppressing approximately half of the intestinal tumors. Interestingly, inhibition of intermediate biomarkers in both models was markedly greater in the distal than the proximal bowel. To mechanistically evaluate this regional selectivity, we assessed cyclo-oxygenase-2 (COX-2) expression in the uninvolved mucosa and demonstrated a 3- to 4-fold excess in the distal relative to the proximal bowel in both MIN mice and AOM-treated rats. We then investigated another putative NSAID target, peroxisome proliferator-activated receptor-delta (PPAR-delta) and demonstrated up-regulation during AOM-induced colonic tumorigenesis. Furthermore, in pre-neoplastic mucosa, there was a 3-fold excess of PPAR-delta in the distal colon. We demonstrate that nabumetone is an effective protective agent in both experimental models of colon carcinogenesis. The striking distal predilection of nabumetone may be, at least partially, explained by distal bowel over-expression of COX-2 and PPAR-delta.

  5. Chemopreventive action of non-steroidal anti-inflammatory drugs on the inflammatory pathways in colon cancer.

    Science.gov (United States)

    Ghanghas, Preety; Jain, Shelly; Rana, Chandan; Sanyal, S N

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-κB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-κB and suppression of anti-inflammatory transcription factor PPAR-γ, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm.

  6. Chemopreventive potential of fungal taxol against 7, 12-dimethylbenz[a]anthracene induced mammary gland carcinogenesis in Sprague Dawley rats.

    Science.gov (United States)

    Gokul Raj, Kathamuthu; Chidambaram, Ranganathan; Varunkumar, Krishnamoorthy; Ravikumar, Vilwanathan; Pandi, Mohan

    2015-11-15

    Breast cancer is the second most prevalent cancer and foremost global public health problem. The present study was designed to appraise the chemopreventive potential of fungal taxol against 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland carcinogenesis in Sprague Dawley rats. After 90 days of tumor induction, fungal and authentic taxol were given intraperitoneally once in a week for four weeks. Infrared thermal imaging analysis, serum biochemical parameters such as lipid peroxidase (LPO), creatinine, enzymic and non enzymic antioxidants, liver markers tests such as alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG) and lipoproteins was analysed. In addition, histopathological observation (breast, kidney and liver), immunohistochemical analysis (p53 and Her2/neu) and western blotting experiments (bcl-2, bax and caspase-9) were performed both in control and experimental animals. In thermal imaging, decreased temperature was observed in rat treated with fungal and authentic taxol when compared to tumor induced rats. The significant decrease in LPO, creatinine, ALT, AST, TC, TG, lipoproteins and increase in enzymic, non-enzymic antioxidants were exemplified in serum of treated groups. Further histopathology, immunohistochemical and western blot analysis (bax, cas-9 and bcl-2) of apoptotic markers in breast tissues clearly showed the anti-carcinogenic property of fungal taxol. Our findings implement that fungal taxol is a potential chemo preventive agent against DMBA induced mammary gland carcinogenesis.

  7. A gene expression signature that can predict green tea exposure and chemopreventive efficacy of lung cancer in mice.

    Science.gov (United States)

    Lu, Yan; Yao, Ruisheng; Yan, Ying; Wang, Yian; Hara, Yukihiko; Lubet, Ronald A; You, Ming

    2006-02-15

    Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Previously, we found that treatment of A/J mice with either green tea (0.6% in water) or a defined green tea catechin extract (polyphenon E; 2.0 g/kg in diet) inhibited lung tumor tumorigenesis. Here, we described expression profiling of lung tissues derived from these studies to determine the gene expression signature that can predict the exposure and efficacy of green tea in mice. We first profiled global gene expressions in normal lungs versus lung tumors to determine genes which might be associated with the tumorigenic process (TUM genes). Gene expression in control tumors and green tea-treated tumors (either green tea or polyphenon E) were compared to determine those TUM genes whose expression levels in green tea-treated tumors returned to levels seen in normal lungs. We established a 17-gene expression profile specific for exposure to effective doses of either green tea or polyphenon E. This gene expression signature was altered both in normal lungs and lung adenomas when mice were exposed to green tea or polyphenon E. These experiments identified patterns of gene expressions that both offer clues for green tea's potential mechanisms of action and provide a molecular signature specific for green tea exposure.

  8. Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605

    Directory of Open Access Journals (Sweden)

    Ralph A. Pietrofesa

    2016-03-01

    Full Text Available The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605 in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs were exposed to crocidolite asbestos fibers (20 µg/cm2 and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA, and levels of 8-iso Prostaglandin F2α (8-isoP. We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM 4-h prior to asbestos exposure. We observed a significant (p < 0.0001, time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time. LGM2605 treatment significantly (p < 0.0001 reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%–88% and 41%–73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment. LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.

  9. Groundwater flow modelling of an abandoned partially open repository

    Energy Technology Data Exchange (ETDEWEB)

    Bockgaard, Niclas (Golder Associates AB (Sweden))

    2010-12-15

    As a part of the license application, according to the nuclear activities act, for a final repository for spent nuclear fuel at Forsmark, the Swedish Nuclear Fuel and Waste Management Company (SKB) has undertaken a series of groundwater flow modelling studies. These represent time periods with different hydraulic conditions and the simulations carried out contribute to the overall evaluation of the repository design and long-term radiological safety. The modelling study presented here serves as an input for analyses of so-called future human actions that may affect the repository. The objective of the work was to investigate the hydraulic influence of an abandoned partially open repository. The intention was to illustrate a pessimistic scenario of the effect of open tunnels in comparison to the reference closure of the repository. The effects of open tunnels were studied for two situations with different boundary conditions: A 'temperate' case with present-day boundary conditions and a generic future 'glacial' case with an ice sheet covering the repository. The results were summarized in the form of analyses of flow in and out from open tunnels, the effect on hydraulic head and flow in the surrounding rock volume, and transport performance measures of flow paths from the repository to surface

  10. Rock and Core Repository Coming Digital

    Science.gov (United States)

    Maicher, Doris; Fleischer, Dirk; Czerniak, Andreas

    2016-04-01

    In times of whole city centres being available by a mouse click in 3D to virtually walk through, reality sometimes becomes neglected. The reality of scientific sample collections not being digitised to the essence of molecules, isotopes and electrons becomes unbelievable to the upgrowing generation of scientists. Just like any other geological institute the Helmholtz Centre for Ocean Research GEOMAR accumulated thousands of specimen. The samples, collected mainly during marine expeditions, date back as far as 1964. Today GEOMAR houses a central geological sample collection of at least 17 000 m of sediment core and more than 4 500 boxes with hard rock samples and refined sample specimen. This repository, having been dormant, missed the onset of the interconnected digital age. Physical samples without barcodes, QR codes or RFID tags need to be migrated and reconnected, urgently. In our use case, GEOMAR opted for the International Geo Sample Number IGSN as the persistent identifier. Consequentially, the software CurationDIS by smartcube GmbH as the central component of this project was selected. The software is designed to handle acquisition and administration of sample material and sample archiving in storage places. In addition, the software allows direct embedding of IGSN. We plan to adopt IGSN as a future asset, while for the initial inventory taking of our sample material, simple but unique QR codes act as "bridging identifiers" during the process. Currently we compile an overview of the broad variety of sample types and their associated data. QR-coding of the boxes of rock samples and sediment cores is near completion, delineating their location in the repository and linking a particular sample to any information available about the object. Planning is in progress to streamline the flow from receiving new samples to their curation to sharing samples and information publically. Additionally, interface planning for linkage to GEOMAR databases Ocean

  11. Characteristics of potential repository wastes. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    1992-07-01

    The LWR spent fuels discussed in Volume 1 of this report comprise about 99% of all domestic non-reprocessed spent fuel. In this report we discuss other types of spent fuels which, although small in relative quantity, consist of a number of diverse types, sizes, and compositions. Many of these fuels are candidates for repository disposal. Some non-LWR spent fuels are currently reprocessed or are scheduled for reprocessing in DOE facilities at the Savannah River Site, Hanford Site, and the Idaho National Engineering Laboratory. It appears likely that the reprocessing of fuels that have been reprocessed in the past will continue and that the resulting high-level wastes will become part of defense HLW. However, it is not entirely clear in some cases whether a given fuel will be reprocessed, especially in cases where pretreatment may be needed before reprocessing, or where the enrichment is not high enough to make reprocessing attractive. Some fuels may be canistered, while others may require special means of disposal. The major categories covered in this chapter include HTGR spent fuel from the Fort St. Vrain and Peach Bottom-1 reactors, research and test reactor fuels, and miscellaneous fuels, and wastes generated from the decommissioning of facilities.

  12. The National Ignition Facility Data Repository

    Energy Technology Data Exchange (ETDEWEB)

    Carey, R W; Adams, P A; Azevedo, S G; Beeler, R G; Foxworthy, C B; Frazier, T M; Hutton, M S; Lagin, L J; Townsend, S L

    2009-09-24

    NIF is the world's largest and most energetic laser experimental system, providing a scientific center to study inertial confinement fusion and matter at extreme energy densities and pressures. This presentation discusses the design, architecture, and implementation of the NIF Data Repository (NDR), which provides for the capture and long-term digital storage of peta-scale datasets produced by conducting experimental campaigns. The NDR is a federated database that provides for the capture of: experimental campaign plans, machine configuration & calibration data, raw experimental results and the processed results produced by scientific workflows. The NDR provides for metadata, pedigree, quality, effectivity, versioning and access control for each of the data categories. A critical capability of the NDR is its extensive data provisioning capabilities and protocols that enable scientists, local and remote alike, to review the results of analysis produced by the NDR's analysis pipeline or to download datasets for offline analysis. The NDR provides for the capture of these locally-produced analysis results to enable both peer review and follow-on automated analysis.

  13. Data sharing, small science and institutional repositories.

    Science.gov (United States)

    Cragin, Melissa H; Palmer, Carole L; Carlson, Jacob R; Witt, Michael

    2010-09-13

    Results are presented from the Data Curation Profiles project research, on who is willing to share what data with whom and when. Emerging from scientists' discussions on sharing are several dimensions suggestive of the variation in both what it means 'to share' and how these processes are carried out. This research indicates that data curation services will need to accommodate a wide range of subdisciplinary data characteristics and sharing practices. As part of a larger set of strategies emerging across academic institutions, institutional repositories (IRs) will contribute to the stewardship and mobilization of scientific research data for e-Research and learning. There will be particular types of data that can be managed well in an IR context when characteristics and practices are well understood. Findings from this study elucidate scientists' views on 'sharable' forms of data-the particular representation that they view as most valued for reuse by others within their own research areas-and the anticipated duration for such reuse. Reported sharing incidents that provide insights into barriers to sharing and related concerns on data misuse are included.

  14. Traits and types of health data repositories.

    Science.gov (United States)

    Wade, Ted D

    2014-01-01

    We review traits of reusable clinical data and offer a typology of clinical repositories with a range of known examples. Sources of clinical data suitable for research can be classified into types reflecting the data's institutional origin, original purpose, level of integration and governance. Primary data nearly always come from research studies and electronic medical records. Registries collect data on focused populations primarily to track outcomes, often using observational research methods. Warehouses are institutional information utilities repackaging clinical care data. Collections organize data from more organizations than a data warehouse, and more original data sources than a registry. Therefore even if they are heavily curated, their level of internal integration, and thus ease of use, can be less than other types. Federations are like collections except that physical control over data is distributed among donor organizations. Federations sometimes federate, giving a second level of organization. While the size, in number of patients, varies widely within each type of data source, populations over 10 K are relatively numerous, and much larger populations can be seen in warehouses and federations. One imagined ideal structure for research progress has been called an "Information Commons". It would have longitudinal, multi-leveled (environmental through molecular) data on a large population of identified, consenting individuals. These are qualities whose achievement would require long term commitment on the part of many data donors, including a willingness to make their data public.

  15. Evolution of near-field physico-chemical characteristics of the SFR repository

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D. [Quintessa Ltd., Nottingham (United Kingdom); Stenhouse, M. [Monitor Scientific LLC, Denver, CO (United States); Benbow, S. [Quintessa Ltd., Henley-on-Thames (United Kingdom)

    2000-08-01

    The evaluation of the post-closure performance of the SFR repository needs to consider time dependent evolution of the repository environment. Time-dependent reaction of near-field barriers (cement, steel, bentonite) with saturating groundwater will lead to the development of hyper alkaline repository pore fluids, chemically reducing conditions, and ultimately, the generation of gas through anaerobic corrosion of metals. Cement and concrete will act as chemical conditioning agents to minimise metal corrosion and ultimately, maximise radioelement sorption. The chemical and physical evolution of cement and concrete through reaction with ambient groundwater will thus affect sorption processes through changes in pH, complexing ligands, and solid surface properties. It is desirable that these changes be incorporated into the safety assessment. The sorption behaviour of radionuclides in cementitious systems has been reviewed in detail. The available evidence from experimental work carried out on the influence of organic materials on the sorption behaviour of radionuclides, indicates that most organic degradation products will not affect sorption significantly at the concentrations expected in a cementitious repository. The notable exception to this conclusion involves the degradation products of cellulose and, in particular, polycarboxylic acids represented by iso-saccharinic acid (ISA). Results using ISA indicate a significant reduction in sorption of Pu, by several orders of magnitude, for an ISA concentration of about 10{sup -3} M. More recent data indicate that the negative effect is not as great, though still significant. Therefore, some scoping calculations are advisable to determine how realistic an ISA concentration of about 10{sup -3} M would be for the SFR repository and to estimate concentrations of other relevant organic compounds, in particular EDTA, for comparison. Scoping calculations relevant to the longevity of hyper alkaline pore fluid conditions at SFR

  16. An evaluation of repository-induced disturbances for a KBS-3 type repository

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D.; McLeod, R.; McEwen, T. [QuantiSci, Melton Mowbray (United Kingdom)

    1998-03-01

    This report considers the potential physical and chemical perturbations caused by the excavation, operation and backfilling and sealing of a KBS-3 type repository for spent fuel in Sweden. Parts of the underground excavations are likely to remain open to the atmosphere for up to several decades. Time-dependent changes to the chemical environment and the properties of the geological formation will be occurring as well as the initial disturbance of construction and subsequent changes after backfilling. In addition, this report also discusses issues that arise from the co-disposal of spent fuel and intermediate level waste. The processes which are likely to act during each stage of a repository from construction through to backfilling and sealing have been reviewed and the degree to which these processes are understood and represented within the performance assessment is discussed. The areas of particular interest are: The coupling of thermal, hydrogeological and mechanical processes with particular reference to the development of the near-field; Understanding the transient process of re-saturation with particular reference to the buffer material surrounding the waste canisters, including chemical changes to the material; The impact of accidental events during the construction and operational phases of work and their possible consequence on the long term performance of the repository; Chemical issues relating to the co-disposal of spent fuel and intermediate level wastes within a single facility. When consideration of transient processes and coupling is discussed, it is apparent that numerical tools and a complete understanding to provide quantitative information is lacking. The importance of the engineered barrier system within the performance assessment for spent fuel disposal is recognised and the emphasis is placed on the understanding of the coupled processes in the evolution in the near-field of the geosphere 45 refs, 4 fig, 2 tabs

  17. Feeding the fledgling repository: starting an institutional repository at an academic health sciences library.

    Science.gov (United States)

    Koopman, Ann; Kipnis, Dan

    2009-01-01

    In 2005, the Scott Memorial Library at Thomas Jefferson University started an institutional repository (IR), the Jefferson Digital Commons (JDC) . Originally intended as a showcase for faculty scholarship, it has evolved to serve also as a university press for original journals and newsletters, and as an institutional archive. Many lessons have been learned about marketing techniques, common IR issues, and advantages of an IR for a library. IR recruitment has come to be viewed as yet another form of collection development and has been integrated into all forms of the Library's outreach. Jefferson's academic health sciences environment has proven similar to other academic environments on issues of acceptance and participation.

  18. National Geoscience Data Repository System, Phase III: Implementation and operation of the repository

    Energy Technology Data Exchange (ETDEWEB)

    American Geological Institute

    2000-03-13

    The American Geological Institute's (AGI) National Geoscience Data Repository System (NGDRS) was initiated in response to the fact that billions of dollars worth of domestic geoscience data are in jeopardy of being irrevocably lost or destroyed as a consequence of the ongoing downsizing of the U.S. energy and minerals industry. Preservation and access to domestic geological and geophysical data are critical to the energy security and economic prosperity of the nation. There is a narrow window of opportunity to act before valuable data are destroyed. The data truly represent a national treasure and immediate steps must be taken to assure their preservation.

  19. Waste package/repository impact study: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1985-09-01

    The Waste Package/Repository Impact Study was conducted to evaluate the feasibility of using the current reference salt waste package in the salt repository conceptual design. All elements of the repository that may impact waste package parameters, i.e., (size, weight, heat load) were evaluated. The repository elements considered included waste hoist feasibility, transporter and emplacement machine feasibility, subsurface entry dimensions, feasibility of emplacement configuration, and temperature limits. The evaluations are discussed in detail with supplemental technical data included in Appendices to this report, as appropriate. Results and conclusions of the evaluations are discussed in light of the acceptability of the current reference waste package as the basis for salt conceptual design. Finally, recommendations are made relative to the salt project position on the application of the reference waste package as a basis for future design activities. 31 refs., 11 figs., 11 tabs.

  20. Study of Womens Health Across the Nation (SWAN) Biospecimen Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The SWAN Repository is the biospecimen bank of the SWAN study. All stored specimens are from the 3,302 SWAN participants, collected across the 14 clinic visits...

  1. On-line repository of audiovisual material feminist research methodology

    Directory of Open Access Journals (Sweden)

    Lena Prado

    2014-12-01

    Full Text Available This paper includes a collection of audiovisual material available in the repository of the Interdisciplinary Seminar of Feminist Research Methodology SIMReF (http://www.simref.net.

  2. Biological General Repository for Interaction Datasets (BioGRID)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BioGRID is an online interaction repository with data on raw protein and genetic interactions from major model organism species. All interaction data are freely...

  3. DRIVER: Building a Sustainable Infrastructure of European Scientific Repositories

    CERN Document Server

    CERN. Geneva

    2007-01-01

    The acronym DRIVER stands for “Digital Repository Infrastructure Vision for European Research”. Ten partners from eight countries have entered into an international partnership, to connect and network as a first step more than 50 physically distributed institutional repositories to one, large-scale, virtual Knowledge Base of European research. Universities and research organisations around the world currently build repositories, whose overall number is estimated to exceed 600 by far. As the academic information landscape is already highly fragmented, DRIVER is the trans-national catalyst to overcome local, isolated efforts and to stop fragmentation by offering one harmonised, virtual knowledge resource. DRIVER currently builds a production quality test-bed to assist the development of a knowledge infrastructure across Europe. DRIVER as a project, funded by the “Research Infrastructure” unit of the European Commission, is also preparing for the future expansion and upgrade of the Digital Repository in...

  4. Spent nuclear fuel for disposal in the KBS-3 repository

    Energy Technology Data Exchange (ETDEWEB)

    Grahn, Per; Moren, Lena; Wiborgh, Maria

    2010-12-15

    The report is included in a set of Production reports, presenting how the KBS-3 repository is designed, produced and inspected. The set of reports is included in the safety report for the KBS-3 repository and repository facility. The report provides input to the assessment of the long-term safety, SR-Site as well as to the operational safety report, SR-Operation. The report presents the spent fuel to be deposited, and the requirements on the handling and selection of fuel assemblies for encapsulation that follows from that it shall be deposited in the KBS-3 repository. An overview of the handling and a simulation of the encapsulation and the resulting canisters to be deposited are presented. Finally, the initial state of the encapsulated spent nuclear fuel is given. The initial state comprises the radionuclide inventory and other data required for the assessment of the long-term safety

  5. Enforcing Interoperability with the Open Archives Initiative Repository Explorer

    OpenAIRE

    2001-01-01

    This presentation gives an overview of the Open Archives Initiative (OAI), protocol validation procedures, interactive browsing, and the OAI repository explorer tool. Presented at the ACM/IEEE JCDL 2001 Conference

  6. Interdisciplinary differences in attitudes towards deposit in institutional repositories

    OpenAIRE

    Allen, James

    2005-01-01

    The attitudes and behaviours of academics from different disciplines towards depositing their work in institutional repositories are compared. This is achieved through the use of a survey strategy, and by examination of the contents of a twenty-five UK institutional repositories. The survey targets humanities academics, and the data is compared to that from previous surveys focusing on scientific, technical and medical (STM) disciplines. The number of humanities documents in institutiona...

  7. NIDDK data repository: a central collection of clinical trial data

    Directory of Open Access Journals (Sweden)

    Hall R David

    2006-04-01

    Full Text Available Abstract Background The National Institute of Diabetes and Digestive and Kidney Diseases have established central repositories for the collection of DNA, biological samples, and clinical data to be catalogued at a single site. Here we present an overview of the site which stores the clinical data and links to biospecimens. Description The NIDDK Data repository is a web-enabled resource cataloguing clinical trial data and supporting information from NIDDK supported studies. The Data Repository allows for the co-location of multiple electronic datasets that were created as part of clinical investigations. The Data Repository does not serve the role of a Data Coordinating Center, but rather as a warehouse for the clinical findings once the trials have been completed. Because both biological and genetic samples are collected from many of the studies, a data management system for the cataloguing and retrieval of samples was developed. Conclusion The Data Repository provides a unique resource for researchers in the clinical areas supported by NIDDK. In addition to providing a warehouse of data, Data Repository staff work with the users to educate them on the datasets as well as assist them in the acquisition of multiple data sets for cross-study analysis. Unlike the majority of biological databases, the Data Repository acts both as a catalogue for data, biosamples, and genetic materials and as a central processing point for the requests for all biospecimens. Due to regulations on the use of clinical data, the ultimate release of that data is governed under NIDDK data release policies. The Data Repository serves as the conduit for such requests.

  8. WORKSHOP ON DEVELOPMENT OF RADIONUCLIDE GETTERS FOR THE YUCCA MOUNTAIN WASTE REPOSITORY

    Energy Technology Data Exchange (ETDEWEB)

    K.C. Holt

    2006-03-13

    One of the important that the U.S. Department of Energy (DOE) is currently undertaking is the development of a high-level nuclear waste repository to be located at Yucca Mountain, Nevada. Concern is generated by the Yucca Mountain Project (YMP) is due to potential releases as groundwater contamination, as described in the Total System Performance Assessment (TSPA). The dose to an off-site individual using this groundwater for drinking and irrigation is dominated by four radionuclides: Tc-99, I-127, Np-237, and U-238. Ideally, this dose would be limited to a single radionuclide, U-238; in other words, YMP would resemble a uranium ore body, a common geologic feature in the Western U.S. For this reason and because of uncertainties in the behavior of Tc-99, I-127, and Np-237, it would be helpful to limit the amount of Tc, I, and Np leaving the repository, which would greatly increase the confidence in the long-term performance of YMP. An approach to limiting the migration of Tc, I, and Np that is complementary to the existing YMP repository design plans is to employ sequestering agents or ''getters'' for these radionuclides such that their migration is greatly hindered, thus decreasing the amount of radionuclide leaving the repository. Development of such getters presents a number of significant challenges. The getter must have a high affinity and high selectivity for the radionuclide in question since there is approximately a 20- to 50-fold excess of other fission products and a 1000-fold excess of uranium in addition to the ions present in the groundwater. An even greater challenge is that the getters must function over a period greater than the half-life of the radionuclide (greater than 5 half-lives would be ideal). Typically, materials with a high affinity for Tc, I, or Np are not sufficiently durable. For example, strong-base ion exchange resins have a very high affinity for TcO{sub 4}{sup -} but are not expected to be durable. On the other

  9. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.

    Science.gov (United States)

    Aviello, Gabriella; Romano, Barbara; Borrelli, Francesca; Capasso, Raffaele; Gallo, Laura; Piscitelli, Fabiana; Di Marzo, Vincenzo; Izzo, Angelo A

    2012-08-01

    Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.

  10. Training Librarians for 21st Century Repository Services: Emerging Trends

    Directory of Open Access Journals (Sweden)

    Helen Emasealu

    2016-05-01

    Full Text Available The paper reviewed the emerging roles of the 21st century librarians, charged with the responsibility to manage repository services across libraries in present-day information technology environment. Librarians need to be trained and empowered with requisite skills and knowledge needed for successful management of the ICT driven repository initiatives that the 21st century demands. Literature was reviewed on the roles and responsibilities of librarians, training needs and opportunities, career path and recruitment of librarians, and community support necessary for effective and efficient implementation and management of repository initiatives. This entails the ability to comprehend trends and change patterns which are essential for providing research focused and user-friendly models in open repository services that are based on thorough analytical understanding of the challenges of emerging trends. To achieve this requires the training and retraining of librarians to reposition them as information specialists in their career path. The role of the library as an integral part of its social environment is to educate the community about the existence of an open repository by building partnership with community-oriented research centres through seminars, workshops, symposium, training, and awareness programmes. The study recommends that librarians should strategize and collaborate with researchers to make open repository an essential research tool.

  11. Chemoprevention of intestinal tumorigenesis by nabumetone: induction of apoptosis and Bcl-2 downregulation

    OpenAIRE

    Roy, H K; Karoski, W J; Ratashak, A; Smyrk, T. C.

    2001-01-01

    Treatment of MIN mice with the nonsteroidal anti-inflammatory drug, nabumetone, resulted in a dose-dependent suppression of intestinal tumorigenesis. In both the uninvolved MIN mouse colonic epithelium and HT-29 colon cancer cells, nabumetone downregulated the anti-apoptotic protein, Bcl-2, with concomitant induction of apoptosis, suggesting a potential mechanism for colon cancer chemoprevention. © 2001 Cancer Research Campaign www.bjcancer.com

  12. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    Science.gov (United States)

    2012-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore... acids effects on PIN development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer...compared to FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing

  13. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

  14. Biomarkers in phase I–II chemoprevention trials: lessons from the NCI experience

    OpenAIRE

    Szabo, Eva

    2015-01-01

    Early phase clinical trials are an essential component of chemopreventive drug development to identify signals of drug efficacy that can subsequently be explored definitively in phase III trials. Whereas phase I trials focus on safety and identification of optimal dose and schedule for cancer prevention, phase II trials focus on intermediate endpoints that are variably related to cancer development. The United States National Cancer Institute supports a programme devoted to early phase cancer...

  15. Quimioprevenção do câncer de mama Current status of breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Vilmar Marques de Oliveira

    2006-12-01

    Full Text Available Quimioprevenção é definida como o uso de agentes químicos naturais ou sintéticos para reverter, suprimir ou prevenir a progressão carcinogênica para carcinoma invasor. Os fármacos que agem como agentes quimiopreventivos contra o câncer de mama são divididos em dois grupos principais: os que previnem cânceres de mama receptor de estrogênio (RE positivos, como os moduladores seletivos do receptor de estrogênio (SERM, inibidores de aromatase, agonistas de GnRH e fitoestrogênios; e os fármacos que previnem os cânceres RE-negativos, como os inibidores da ciclooxigenase-2 (COX-2, retinóides, as estatinas, os inibidores do receptor tirosina quinase, o anticorpo monoclonal contra HER-2 e os inbidores da telomerase. Resultados do estudo conduzido pelo NSABP que comparou o tamoxifeno com o raloxifeno (STAR, avaliando a eficácia na redução de risco, assim como a toxicidade desses dois SERMs em uma população similar e de alto risco para câncer de mama, demonstrou que o raloxifeno é tão efetivo quanto o tamoxifeno na redução de risco de câncer de mama invasor (p=0,83 e apresentou menor risco de eventos tromboembólicos e catarata; todavia, exibiu maior risco de carcinoma não invasor, porém sem significância estatística. Baseado nos dados promissores que revelaram diminuição de risco de câncer de mama contralateral em estudos de adjuvância, alguns inibidores de aromatase, incluindo o letrozol, anastrazol e exemestane, estão sendo incorporados em investigações para avaliar sua eficácia como agentes preventivos de alto risco em mulheres. Os inibidores de COX-2 demonstraram sua eficácia na prevenção do câncer de mama em estudos caso-controle e coorte, sendo necessários estudos aleatórios para atestar sua eficácia. O resultado positivo de alguns ensaios clínicos na prevenção do câncer de mama em populações de alto risco sugere que a quimioprevenção é uma estratégia racional e atraente.Chemoprevention is

  16. International perspective on repositories for low level waste

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, Ulla; Pers, Karin; Almen, Ylva (SKB International AB (Sweden))

    2011-12-15

    Nuclear energy production gives rise to different types of radioactive waste. The use of nuclear isotopes within the research, industry and medical sectors also generates radioactive waste. To protect man and the environment from radiation the waste is isolated and contained by deposition in repositories. These repositories may have various designs regarding location, barriers etc depending on the potential danger of the waste. In Sweden, low- and intermediate level waste (LILW) is disposed of in the SFR repository in Forsmark. The repository is located 60 metres down into the bedrock under the bottom of the sea and covered by 6 metres of water. It is planned to extend SFR to accommodate decommissioning waste from the dismantling of the Swedish nuclear power facilities and also for the additional operation waste caused by the planned prolonged operation time. When planning the extension consultations will be carried out with the host municipality, authorities, organisations and general public. In planning the extension, SKB has performed a worldwide compilation of how other countries have, or plan to, handle the final disposal of similar wastes. The aim of this report is to give a brief description of LILW repositories worldwide; including general brief descriptions of many facilities, descriptions of the waste and the barriers as well as safety assessments for a few chosen repositories which represent different designs. The latter is performed, where possible, to compare certain features against the Swedish SFR. To provide a background and context to this study, international organisations and conventions are also presented along with internationally accepted principles regarding the management of radioactive waste. Similar to SFR, suitable locations for the repositories have, in many countries, been found at sites that already have, or used to have nuclear activities, such as reactor sites. Abandoned and disused mines, such as the salt mines in Germany, also

  17. IMPLEMENTATION AND OPERATION OF THE REPOSITORY

    Energy Technology Data Exchange (ETDEWEB)

    Marcus Milling

    2003-10-01

    The NGDRS has facilitated 85% of cores, cuttings, and other data identified available for transfer to the public sector. Over 12 million linear feet of cores and cuttings, in addition to large numbers of paleontological samples and are now available for public use. To date, with industry contributions for program operations and data transfers, the NGDRS project has realized a 6.5 to 1 return on investment to Department of Energy funds. Large-scale transfers of seismic data have been evaluated, but based on the recommendation of the NGDRS steering committee, cores have been given priority because of the vast scale of the seismic data problem relative to the available funding. The rapidly changing industry conditions have required that the primary core and cuttings preservation strategy evolve as well. Additionally, the NGDRS clearinghouse is evaluating the viability of transferring seismic data covering the western shelf of the Florida Gulf Coast. AGI remains actively involved in working to realize the vision of the National Research Council's report of geoscience data preservation. GeoTrek has been ported to Linux and MySQL, ensuring a purely open-source version of the software. This effort is key in ensuring long-term viability of the software so that is can continue basic operation regardless of specific funding levels. Work has been on a major revision of GeoTrek, using the open-source MapServer project and its related MapScript language. This effort will address a number of key technology issues that appear to be rising for 2003, including the discontinuation of the use of Java in future Microsoft operating systems. The recent donation of BPAmoco's Houston core facility to the Texas Bureau of Economic Geology has provided substantial short-term relief of the space constraints for public repository space.

  18. Eprints Institutional Repository Software: A Review

    Directory of Open Access Journals (Sweden)

    Mike R. Beazley

    2011-01-01

    Full Text Available Setting up an institutional repository (IR can be a daunting task. There are many software packages out there, some commercial, some open source, all of which offer different features and functionality. This article will provide some thoughts about one of these software packages: Eprints. Eprints was one of the first IR software packages to appear and has been available for 10 years. It is under continual development by its creators at the University of Southampton and the current version is v3.2.3. Eprints is open-source, meaning that anyone can download and make use of the software for free and the software can be modified however the user likes. This presents clear advantages for institutions will smaller budgets and also for institutions that have programmers on staff. Eprints requires some additional software to run: Linux, Apache, MySQL, and Perl. This software is all open-source and already present on the servers of many institutions. There is now a version of Eprints that will run on Windows servers as well, which will make the adoption of Eprints even easier for some. In brief, Eprints is an excellent choice for any institution looking to get an IR up and running quickly and easily. Installation is straightforward as is the initial configuration. Once the IR is up and running, users may upload documents and provide the necessary metadata for the records by filling out a simple web form. Embargoes on published documents are handled elegantly by the software, and the software links to the SHERPA/RoMEO database so authors can easily verify their rights regarding IR submissions. Eprints has some drawbacks, which will be discussed later in the review, but on the whole it is easy to recommend to anyone looking to start an IR. However, It is less clear that an institution with an existing IR based on another software package should migrate to Eprints.

  19. Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds.

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin

    2011-09-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

  20. Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

    Science.gov (United States)

    Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

    2016-02-01

    Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption.

  1. LIFE Materials: Fuel Cycle and Repository Volume 11

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, H; Blink, J A

    2008-12-12

    The fusion-fission LIFE engine concept provides a path to a sustainable energy future based on safe, carbon-free nuclear power with minimal nuclear waste. The LIFE design ultimately offers many advantages over current and proposed nuclear energy technologies, and could well lead to a true worldwide nuclear energy renaissance. When compared with existing and other proposed future nuclear reactor designs, the LIFE engine exceeds alternatives in the most important measures of proliferation resistance and waste minimization. The engine needs no refueling during its lifetime. It requires no removal of fuel or fissile material generated in the LIFE engine. It leaves no weapons-attractive material at the end of life. Although there is certainly a need for additional work, all indications are that the 'back end' of the fuel cycle does not to raise any 'showstopper' issues for LIFE. Indeed, the LIFE concept has numerous benefits: (1) Per unit of electricity generated, LIFE engines would generate 20-30 times less waste (in terms of mass of heavy metal) requiring disposal in a HLW repository than does the current once-through fuel cycle. (2) Although there may be advanced fuel cycles that can compete with LIFE's low mass flow of heavy metal, all such systems require reprocessing, with attendant proliferation concerns; LIFE engines can do this without enrichment or reprocessing. Moreover, none of the advanced fuel cycles can match the low transuranic content of LIFE waste. (3) The specific thermal power of LIFE waste is initially higher than that of spent LWR fuel. Nevertheless, this higher thermal load can be managed using appropriate engineering features during an interim storage period, and could be accommodated in a Yucca-Mountain-like repository by appropriate 'staging' of the emplacement of waste packages during the operational period of the repository. The planned ventilation rates for Yucca Mountain would be sufficient for LIFE waste

  2. Have digital repositories come of age? The views of library directors

    Directory of Open Access Journals (Sweden)

    David Nicholas

    2013-12-01

    Full Text Available This survey of approximately 150 repositories assessed the achievements, impact, and success of digital repositories. Results show that while the size and use of repositories has been relatively modest, almost half of all institutions either have, or are planning, a repository mandate requiring deposit and small gains have been made in raising the profile of the library within the institution. Repositories, then, have made a good deal of progress, but they have not quite come of age.

  3. Principal organic materials in a repository for spent nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Hallbeck, Lotta (Microbial Analytics Sweden AB, Moelnlycke (Sweden))

    2010-01-15

    The largest pool of organic material in a repository at closure is the organic material in the bentonite in buffer and backfill. It is impossible to make any assumptions as to how much of this material will be available for biodegradation, since the character of the material is unknown. However, it is unlikely that this organic material can dissolve in groundwater unless the bentonite loses its swelling capacity. The second largest pool will be the biofilms formed on the rock surfaces. This assumption presupposes that no cleaning is undertaken before repository closure. The third largest pool is the organic material produced by microorganisms using hydrogen from the anaerobic corrosion of iron in steel as an energy source. The following provides summary descriptions of the different pools of organic material that will remain in the repository: 1. Microorganisms. Their effect would mainly be to reduce the redox potential soon after repository closure. They may contribute to the depletion of the oxygen entrapped during repository construction, an effect that would not jeopardise repository stability. If the dominant microorganisms in the anaerobic environment are sulphate-reducing bacteria, oxidation of organic material would lead to the formation of HS-. The produced sulphide could corrode the copper canisters under anaerobic conditions if it reaches them. Another effect of microorganisms would be to increase the complexing capacity of the groundwater due to excreted metabolites. The impact of these compounds is not yet clear, although it will surely not be very important, due to the small amounts of such substances. 2. Materials in the ventilation air. Their effect will probably be to help maintain reducing conditions in the area, although this effect will likely be minimal or negligible. 3. Construction materials. Among these materials, we emphasise the organic materials present in concrete, asphalt, bentonite, and wood. Hydrocarbons from asphalt may help reduce

  4. Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.

    Directory of Open Access Journals (Sweden)

    Nancy C Sambol

    Full Text Available The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children.Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability of candidate chemoprevention regimens for a reference population of 1-2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose.Once daily doses of 320 mg for three days (960 mg total at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%, while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention.Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field-based clinical studies of young

  5. An open data repository and a data processing software toolset of an equivalent Nordic grid model matched to historical electricity market data.

    Science.gov (United States)

    Vanfretti, Luigi; Olsen, Svein H; Arava, V S Narasimham; Laera, Giuseppe; Bidadfar, Ali; Rabuzin, Tin; Jakobsen, Sigurd H; Lavenius, Jan; Baudette, Maxime; Gómez-López, Francisco J

    2017-04-01

    This article presents an open data repository, the methodology to generate it and the associated data processing software developed to consolidate an hourly snapshot historical data set for the year 2015 to an equivalent Nordic power grid model (aka Nordic 44), the consolidation was achieved by matching the model׳s physical response w.r.t historical power flow records in the bidding regions of the Nordic grid that are available from the Nordic electricity market agent, Nord Pool. The model is made available in the form of CIM v14, Modelica and PSS/E (Siemens PTI) files. The Nordic 44 model in Modelica and PSS/E were first presented in the paper titled "iTesla Power Systems Library (iPSL): A Modelica library for phasor time-domain simulations" (Vanfretti et al., 2016) [1] for a single snapshot. In the digital repository being made available with the submission of this paper (SmarTSLab_Nordic44 Repository at Github, 2016) [2], a total of 8760 snapshots (for the year 2015) that can be used to initialize and execute dynamic simulations using tools compatible with CIM v14, the Modelica language and the proprietary PSS/E tool are provided. The Python scripts to generate the snapshots (processed data) are also available with all the data in the GitHub repository (SmarTSLab_Nordic44 Repository at Github, 2016) [2]. This Nordic 44 equivalent model was also used in iTesla project (iTesla) [3] to carry out simulations within a dynamic security assessment toolset (iTesla, 2016) [4], and has been further enhanced during the ITEA3 OpenCPS project (iTEA3) [5]. The raw, processed data and output models utilized within the iTesla platform (iTesla, 2016) [4] are also available in the repository. The CIM and Modelica snapshots of the "Nordic 44" model for the year 2015 are available in a Zenodo repository.

  6. Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma.

    Science.gov (United States)

    Nihal, Minakshi; Ahmad, Nihal; Mukhtar, Hasan; Wood, Gary S

    2005-04-20

    Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

  7. Proceedings of the scientific visit on crystalline rock repository development.

    Energy Technology Data Exchange (ETDEWEB)

    Mariner, Paul E.; Hardin, Ernest L.; Miksova, Jitka [RAWRA, Czech Republic

    2013-02-01

    A scientific visit on Crystalline Rock Repository Development was held in the Czech Republic on September 24-27, 2012. The visit was hosted by the Czech Radioactive Waste Repository Authority (RAWRA), co-hosted by Sandia National Laboratories (SNL), and supported by the International Atomic Energy Agency (IAEA). The purpose of the visit was to promote technical information exchange between participants from countries engaged in the investigation and exploration of crystalline rock for the eventual construction of nuclear waste repositories. The visit was designed especially for participants of countries that have recently commenced (or recommenced) national repository programmes in crystalline host rock formations. Discussion topics included repository programme development, site screening and selection, site characterization, disposal concepts in crystalline host rock, regulatory frameworks, and safety assessment methodology. Interest was surveyed in establishing a %E2%80%9Cclub,%E2%80%9D the mission of which would be to identify and address the various technical challenges that confront the disposal of radioactive waste in crystalline rock environments. The idea of a second scientific visit to be held one year later in another host country received popular support. The visit concluded with a trip to the countryside south of Prague where participants were treated to a tour of the laboratory and underground facilities of the Josef Regional Underground Research Centre.

  8. Federated repositories of X-ray diffraction images.

    Science.gov (United States)

    Androulakis, Steve; Schmidberger, Jason; Bate, Mark A; DeGori, Ross; Beitz, Anthony; Keong, Cyrus; Cameron, Bob; McGowan, Sheena; Porter, Corrine J; Harrison, Andrew; Hunter, Jane; Martin, Jennifer L; Kobe, Bostjan; Dobson, Renwick C J; Parker, Michael W; Whisstock, James C; Gray, Joan; Treloar, Andrew; Groenewegen, David; Dickson, Neil; Buckle, Ashley M

    2008-07-01

    There is a pressing need for the archiving and curation of raw X-ray diffraction data. This information is critical for validation, methods development and improvement of archived structures. However, the relatively large size of these data sets has presented challenges for storage in a single worldwide repository such as the Protein Data Bank archive. This problem can be avoided by using a federated approach, where each institution utilizes its institutional repository for storage, with a discovery service overlaid. Institutional repositories are relatively stable and adequately funded, ensuring persistence. Here, a simple repository solution is described, utilizing Fedora open-source database software and data-annotation and deposition tools that can be deployed at any site cheaply and easily. Data sets and associated metadata from federated repositories are given a unique and persistent handle, providing a simple mechanism for search and retrieval via web interfaces. In addition to ensuring that valuable data is not lost, the provision of raw data has several uses for the crystallographic community. Most importantly, structure determination can only be truly repeated or verified when the raw data are available. Moreover, the availability of raw data is extremely useful for the development of improved methods of image analysis and data processing.

  9. Criticality issues with highly enriched fuels in a repository environment

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, L.L. [Lockheed Martin Idaho Technologies Co., Idaho Falls, ID (United States); Sanchez, L.C.; Rath, J.S. [Sandia National Labs., Albuquerque, NM (United States)

    1998-03-01

    This paper presents preliminary analysis of a volcanic tuff repository containing a combination of low enrichment commercial spent nuclear fuels (SNF) and DOE-owned SNF packages. These SNFs were analyzed with respect to their criticality risks. Disposal of SNF packages containing significant fissile mass within a geologic repository must comply with current regulations relative to criticality safety during transportation and handling within operational facilities. However, once the repository is closed, the double contingency credits for criticality safety are subject to unremediable degradation, (e.g., water intrusion, continued presence of neutron absorbers in proximity to fissile material, and fissile material reconfiguration). The work presented in this paper focused on two attributes of criticality in a volcanic tuff repository for near-field and far-field scenarios: (1) scenario conditions necessary to have a criticality, and (2) consequences of a nuclear excursion that are components of risk. All criticality consequences are dependent upon eventual water intrusion into the repository and subsequent breach of the disposal package. Key criticality parameters necessary for a critical assembly are: (1) adequate thermal fissile mass, (2) adequate concentration of fissile material, (3) separation of neutron poison from fissile materials, and (4) sufficient neutron moderation (expressed in units of moderator to fissile atom ratios). Key results from this study indicated that the total energies released during a single excursion are minimal (comparable to those released in previous solution accidents), and the maximum frequency of occurrence is bounded by the saturation and temperature recycle times, thus resulting in small criticality risks.

  10. Implementing digital preservation in repositories: Knowledge and practices

    Directory of Open Access Journals (Sweden)

    Caterina Groposo Pavão

    2016-09-01

    Full Text Available Digital preservation has to be undertaken by institutional repositories, which are responsible for the preservation of the scientific output from academic institutions. However, due to the constant evolution of the field, to gain domain knowledge and recognise best practices is a complex task for people responsible for digital preservation in those institutions. Digital preservation research, practices and solutions address specific problems, such as formats, curation, reference models, authenticity, policies and preservation plans, tools, etc., while stakeholders need an integrated, contextualized and applicable overview. This paper focuses on the implementation of digital preservation in repositories, from the perspective of the team responsible for the project, regarding the necessary knowledge and best practices. Initially, it defines and contextualizes digital preservation repositories. The following section presents a conceptual model of digital preservation, synthesized from conceptual models developed in influential projects in the field, which allows us to identify the domain knowledge in digital preservation. Finally, aspects represented in the model are discussed in the light of the performance of teams implementing digital preservation repositories. It provides recommendations, guides and examples that may be useful for the implementation of digital preservation. It points to the need to strengthen the relationship between domain knowledge in digital preservation repositories with practices developed in numerous projects developed worldwide.

  11. Digital repositories certification: the Data Seal of Approval

    Directory of Open Access Journals (Sweden)

    Stefano Allegrezza

    2015-09-01

    Full Text Available In recent years, it has become increasingly common to entrust records to digital repositories; this assumes an implicit confidence in the repositories reliability, and therefore is urgent to identify the criteria on which to evaluate them. The Data Seal of Approval is a set of sixteen criteria that can be used to ensure that archived data can still be found, understood and used in the future. It is a basic level of certification but it is very useful to highlight the strengths and weaknesses of the deposit; in any case, it constitutes a solid basis for further certification of compliance to ISO 16363 or DIN 31644. The aim of this article is to provide an overview of Data Seal of Approval in the wider context of digital repositories' certification.

  12. Functional requirements for a central research imaging data repository.

    Science.gov (United States)

    Franke, Thomas; Gruetz, Romanus; Dickmann, Frank

    2013-01-01

    The current situation at many university medical centers regarding the management of biomedical research imaging data leaves much to be desired. In contrast to the recommendations of the German Research Foundation (DFG) and the German Council of Sciences and Humanities regarding the professional management of research data, there are commonly many individual data pools for research data in each institute and the management remains the responsibility of the researcher. A possible solution for this situation would be to install local central repositories for biomedical research imaging data. In this paper, we developed a scenario based on abstracted use-cases for institutional research undertakings as well as collaborative biomedical research projects and analyzed the functional requirements that a local repository would have to fulfill. We determined eight generic categories of functional requirements, which can be viewed as a basic guideline for the minimum functionality of a central repository for biomedical research imaging data.

  13. Archaeological data as a basis for repository marker design

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, M.F.

    1982-10-01

    This report concerns the development of a marking system for a nuclear waste repository which is very likely to survive for 10,000 years. In order to provide a background on the subject, and for the preliminary design presented in this report, a discussion is presented about the issues involved in human interference with the repository system and the communication of information. A separate chapter summarizes six ancient man-made monuments including: materials, effects of associated textual information on our understanding of the monument, and other features of the ancient monument relevant to marking a repository site. The information presented in the two chapters is used to provide the basis and rationale for a preliminary marker system design presented in a final chapter. 86 refs., 22 figs., 1 tab.

  14. Reliable predictions of waste performance in a geologic repository

    Energy Technology Data Exchange (ETDEWEB)

    Pigford, T.H.; Chambre, P.L.

    1985-08-01

    Establishing reliable estimates of long-term performance of a waste repository requires emphasis upon valid theories to predict performance. Predicting rates that radionuclides are released from waste packages cannot rest upon empirical extrapolations of laboratory leach data. Reliable predictions can be based on simple bounding theoretical models, such as solubility-limited bulk-flow, if the assumed parameters are reliably known or defensibly conservative. Wherever possible, performance analysis should proceed beyond simple bounding calculations to obtain more realistic - and usually more favorable - estimates of expected performance. Desire for greater realism must be balanced against increasing uncertainties in prediction and loss of reliability. Theoretical predictions of release rate based on mass-transfer analysis are bounding and the theory can be verified. Postulated repository analogues to simulate laboratory leach experiments introduce arbitrary and fictitious repository parameters and are shown not to agree with well-established theory. 34 refs., 3 figs., 2 tabs.

  15. Interaction of Plutonium with Bacteria in the Repository Environment

    Energy Technology Data Exchange (ETDEWEB)

    Gillow, J. B.; Francis, A. J.; Lucero, D. A.; Papenguth, H. W.

    2000-07-01

    Microorganisms in the nuclear waste repository environment may interact with plutonium through (1) sorption, (2) intracellular accumulation, and (3) transformation speciation. These interactions may retard or enhance the mobility of Pu by precipitation reactions, biocolloid formation, or production of more soluble species. Current and planned radioactive waste repository environments, such as deep subsurface halite and granite formations, are considered extreme relative to life processes in the near-surface terrestrial environment. There is a paucity of information on the biotransformation of radionuclides by microorganisms present in such extreme environments. In order to gain a better understanding of the interaction of plutonium with microorganisms present in the waste repository sites we investigated a pure culture (Halomonas sp.) and a mixed culture of bacteria (Haloarcula sinaiiensis, Marinobacter hydrocarbonoclasticus, Altermonas sp., and a {gamma}-proteobacterium) isolated from the Waste Isolation Pilot Plant (WIPP) site and an Acetobacterium sp. from alkaline groundwater at the Grimsel Test Site in Switzerland.

  16. Institutional Repository saber.ula.ve: A testimonial perspective

    CERN Document Server

    Briceno, Y; Nunez, L A; Salager-Meyer, F; Rojas, A; Torrens, R

    2009-01-01

    In this paper, we describe our decade-long experience of building and operating one of the most active Institutional Repository in the world: www.saber.ula.ve (University of the Andes, Merida-Venezuela). In order to share our experience with other institutions, we firstly explain the steps we followed to preserve and disseminate the scientific production of the University of Los Andes' researchers. We then present some recent quantitative results about our repository activities and we outline some methodological guidelines that could be applied in order to replicate similar experiences. These guidelines list the ingredients or building blocks as well as the processes followed for developing and maintaining the services of an Institutional Repository. These include technological infrastructure; institutional policies on preservation, publication and dissemination of knowledge; recommendations on incentives for open access publication; the process of selection, testing and adaptation of technological tools; th...

  17. Public concerns and choices regarding nuclear waste repositories

    Energy Technology Data Exchange (ETDEWEB)

    Rankin, W.L.; Nealey, S.M.

    1981-06-01

    Survey research on nuclear power issues conducted in the late 1970's has determined that nuclear waste management is now considered to be one of the most important nuclear power issues both by the US public and by key leadership groups. The purpose of this research was to determine the importance placed on specific issues associated with high-level waste disposal. In addition, policy option choices were asked regarding the siting of both low-level and high-level nuclear waste repositories. A purposive sampling strategy was used to select six groups of respondents. Averaged across the six respondent groups, the leakage of liquid wastes from storage tanks was seen as the most important high-level waste issue. There was also general agreement that the issue regarding water entering the final repository and carrying radioactive wastes away was second in importance. Overall, the third most important issue was the corrosion of the metal containers used in the high-level waste repository. There was general agreement among groups that the fourth most important issue was reducing safety to cut costs. The fifth most important issue was radioactive waste transportation accidents. Overall, the issues ranked sixth and seventh were, respectively, workers' safety and earthquakes damaging the repository and releasing radioactivity. The eighth most important issue, overall, was regarding explosions in the repository from too much radioactivity, which is something that is not possible. There was general agreement across all six respondent groups that the two least important issues involved people accidentally digging into the site and the issue that the repository might cost too much and would therefore raise electricity bills. These data indicate that the concerns of nuclear waste technologists and other public groups do not always overlap.

  18. Final repository for Denmark's low- and intermediate level radioactive waste

    Science.gov (United States)

    Nilsson, B.; Gravesen, P.; Petersen, S. S.; Binderup, M.

    2012-12-01

    Bertel Nilsson*, Peter Gravesen, Stig A. Schack Petersen, Merete Binderup Geological Survey of Denmark and Greenland (GEUS), Øster Voldgade 10, 1350 Copenhagen, Denmark, * email address bn@geus.dk The Danish Parliament decided in 2003 that the temporal disposal of the low- and intermediate level radioactive waste at the nuclear facilities at Risø should find another location for a final repository. The Danish radioactive waste must be stored on Danish land territory (exclusive Greenland) and must hold the entire existing radioactive waste, consisting of the waste from the decommissioning of the nuclear facilities at Risø, and the radioactive waste produced in Denmark from hospitals, universities and industry. The radioactive waste is estimated to a total amount of up to 10,000 m3. The Geological Survey of Denmark and Greenland, GEUS, is responsible for the geological studies of suitable areas for the repository. The task has been to locate and recognize non-fractured Quaternary and Tertiary clays or Precambrian bedrocks with low permeability which can isolate the radioactive waste from the surroundings the coming more than 300 years. Twenty two potential areas have been located and sequential reduced to the most favorable two to three locations taking into consideration geology, hydrogeology, nature protection and climate change conditions. Further detailed environmental and geology investigations will be undertaken at the two to three potential localities in 2013 to 2015. This study together with a study of safe transport of the radioactive waste and an investigation of appropriate repository concepts in relation to geology and safety analyses will constitute the basis upon which the final decision by the Danish Parliament on repository concept and repository location. The final repository is planned to be established and in operation at the earliest 2020.

  19. Implementation of the Brazilian National Repository - RBMN Project - 13008

    Energy Technology Data Exchange (ETDEWEB)

    Cassia Oliveira de Tello, Cledola [CDTN - Center for Development of Nuclear Technology, Av. Presidente Antonio Carlos, 6.627 - Campus UFMG - Pampulha, CEP 31270-901 - Belo Horizonte - MG (Brazil)

    2013-07-01

    Ionizing radiation in Brazil is used in electricity generation, medicine, industry, agriculture and for research and development purposes. All these activities can generate radioactive waste. At this point, in Brazil, the use of nuclear energy and radioisotopes justifies the construction of a national repository for radioactive wastes of low and intermediate-level. According to Federal Law No. 10308, Brazilian National Commission for Nuclear Energy (CNEN) is responsible for designing and constructing the intermediate and final storages for radioactive wastes. Additionally, a restriction on the construction of Angra 3 is that the repository is under construction until its operation start, attaining some requirements of the Brazilian Environmental Regulator (IBAMA). Besides this NPP, in the National Energy Program is previewed the installation of four more plants, by 2030. In November 2008, CNEN launched the Project RBMN (Repository for Low and Intermediate-Level Radioactive Wastes), which aims at the implantation of a National Repository for disposal of low and intermediate-level of radiation wastes. This Project has some aspects that are unique in the Brazilian context, especially referring to the time between its construction and the end of its institutional period. This time is about 360 years, when the area will be released for unrestricted uses. It means that the Repository must be safe and secure for more than three hundred years, which is longer than half of the whole of Brazilian history. This aspect is very new for the Brazilian people, bringing a new dimension to public acceptance. Another point is this will be the first repository in South America, bringing a real challenge for the continent. The current status of the Project is summarized. (authors)

  20. The Proposed Yucca Mountain Repository From A Corrosion Perspective

    Energy Technology Data Exchange (ETDEWEB)

    J.H. Payer

    2005-03-10

    Corrosion is a primary determinant of waste package performance at the proposed Yucca Mountain Repository and will control the delay time for radionuclide transport from the waste package. Corrosion is the most probable and most likely degradation process that will determine when packages will be penetrated and the shape size and distribution of those penetrations. The general issues in corrosion science, materials science and electrochemistry are well defined, and the knowledge base is substantial for understanding corrosion processes. In this paper, the Yucca Mountain Repository is viewed from a corrosion perspective.

  1. DRIVER: Building a Sustainable Infrastructure of European Scientific Repositories

    Directory of Open Access Journals (Sweden)

    Norbert Lossau

    2008-11-01

    Full Text Available DRIVER has a clear vision: All research institutions in Europe and worldwide make all their research publications openly accessible through institutional repositories. The vision follows the Berlin Declaration, which called in October 2003 for ‘free and unrestricted access to sciences and human knowledge representation worldwide’. Initiated by the internationally renowned German research organisation the Max-Planck-Society, and signed by many international research organisations and institutes, the Berlin Declaration has set a political statement. In building a sustainable infrastructure for scientific repositories, DRIVER brings to this statement the reality of scholarly communication in the future.

  2. Analytical performance models for geologic repositories. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Chambre, P.L.; Pigford, T.H.; Fujita, A.; Kanki, T.; Kobayashi, A.; Lung, H.; Ting, D.; Sato, Y.; Zavoshy, S.J.

    1982-10-01

    This report presents analytical solutions of the dissolution and hydrogeologic transport of radionuclides in geologic repositories. Numerical examples are presented to demonstrate the equations resulting from these analyses. The subjects treated in this report are: solubility-limited transport with transverse dispersion (chapter 2); transport of a radionuclide chain with nonequilibrium chemical reactions (chapter 3); advective transport in a two-dimensional flow field (chapter 4); radionuclide transport in fractured media (chapter 5); a mathematical model for EPA's analysis of generic repositories (chapter 6); and dissolution of radionuclides from solid waste (chapter 7). Volume 2 contains chapters 5, 6, and 7.

  3. Corrosion of the copper canister in the repository environment

    Energy Technology Data Exchange (ETDEWEB)

    Hermansson, H.P.; Eriksson, Sture [Studsvik Material AB, Nykoeping (Sweden)

    1999-12-01

    The present report accounts for studies on copper corrosion performed at Studsvik Material AB during 1997-1999 on commission by SKI. The work has been focused on localised corrosion and electrochemistry of copper in the repository environment. The current theory of localised copper corrosion is not consistent with recent practical experiences. It is therefore desired to complete and develop the theory based on knowledge about the repository environment and evaluations of previous as well as recent experimental and field results. The work has therefore comprised a thorough compilation and up-date of literature on copper corrosion and on the repository environment. A selection of a 'working environment', defining the chemical parameters and their ranges of variation has been made and is used as a fundament for the experimental part of the work. Experiments have then been performed on the long-range electrochemical behaviour of copper in selected environments simulating the repository. Another part of the work has been to further develop knowledge about the thermodynamic limits for corrosion in the repository environment. Some of the thermodynamic work is integrated here. Especially thermodynamics for the system Cu-Cl-H-O up to 150 deg C and high chloride concentrations are outlined. However, there is also a rough overview of the whole system Cu-Fe-Cl-S-C-H-O as a fundament for the discussion. Data are normally accounted as Pourbaix diagrams. Some of the conclusions are that general corrosion on copper will probably not be of significant importance in the repository as far as transportation rates are low. However, if such rates were high, general corrosion could be disastrous, as there is no passivation of copper in the highly saline environment. The claim on knowledge of different kinds of localised corrosion and pitting is high, as pitting damages can shorten the lifetime of a canister dramatically. Normal pitting can happen in oxidising environment, but

  4. Chemopreventive Effect of Tadalafil in Cisplatin-Induced Nephrotoxicity in Rats.

    Science.gov (United States)

    Adeneye, A A; Benebo, A S

    2016-08-30

    Nephrotoxicity remains a common untoward effect of cisplatin therapy with limited effective chemopreventive options available till date. This study aims to evaluate the possible chemopreventive effect and mechanism(s) of action of 2 mgkg-1 and 5 mgkg-1 of Tadalafil in cisplatin-induced nephrotoxic rats. In this study, twenty-five male Wistar rats were randomly divided into five groups (n = 5 rats per group) and daily pretreated with oral doses of distilled water (10 mLkg-1), ascorbic acid (100 mgkg-1), Tadalafil (2 mgkg-1 and 5 mgkg-1) for 7 days before cisplatin (5 mgkg-1, intraperitoneal) was administered. 72 hours post-cisplatin injections, rats were sacrificed humanely and blood samples for serum electrolytes, urea and creatinine and renal tissues for reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malonialdehyde dehydrogenase (MAD) assays and histopathology were collected. Results showed that cisplatin injection caused significant decreases in the serum sodium (Na+), potassium (K+), bicarbonate (HCO3-), calcium (Ca2+), phosphate (PO42-) and concomitant significant increases in the serum urea and creatinine levels. In addition, there were significant decreases in the renal tissue GSH, SOD, CAT and increased MAD and GSH-Px levels which were corroborated by histopathological features of tubulonephritis. However, these histo-biochemical alterations were significantly attenuated by ascorbic acid and Tadalafil pretreatments. Overall, results of this study showed the chemopreventive potential of Tadalafil against cisplatin-induced nephrotoxicity which was possibly mediated via antioxidant and anti-lipoperoxidation mechanisms.

  5. Antiproliferative and cancer-chemopreventive properties of sulfated glycosylated extract derived from Leucaena leucocephala

    Directory of Open Access Journals (Sweden)

    Gamal-Eldeen Amira

    2007-01-01

    Full Text Available This work aimed to prove that simple chemical modification could provide new cancer chemopreventive and/or anticancer properties to the inactive extracted polysaccharide derived from Leucaena leucocephala . Polysaccharides were extracted from Leucaena leucocephala seeds and its 2,4-pentanedione-treated derivative (glycosylated form was prepared, which is further sulphated to give sulphated glycosylated form. Estimation of their anti-initiation activity, modulation of carcinogen metabolism, was indicated by the inhibition cytochrome P450 1A (CYP1A and the induction of glutathione-S-transferases (GSTs. Anti-proliferation activity was investigated by MTT assay against human hepatocarcinoma (HepG2, breast carcinoma (MCF-7 and lymphoblastic leukemia (1301. Apoptosis/necrosis and cell cycle were analyzed by flow cytometry. The results revealed that glycosylated form inhibited both CYP1A and GSTs, while sulphated glycosylated form not only inhibited CYP1A, but also induced the GSTs. Unlike GE, sulphated glycosylated form possessed a significant anti-proliferative activity against different cell lines. Analysis of HepG2 cell cycle phases demonstrated that glycosylated form led to a delay of G2/M-phase, while sulphated glycosylated form led to a concomitant arrest in S- and G2/M-phases. Investigation of apoptosis/necrosis ratio demonstrated that both of glycosylated form and sulphated glycosylated form induced HepG2 cell death by necrosis, but not apoptosis. Unmodified crude extract was neither active as cancer chemopreventive nor as anti-proliferative. In conclusion, chemical modification of Leucaena gum induced its cancer chemopreventive and anti-proliferative activities.

  6. Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer.

    Science.gov (United States)

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Al-Tantawy, Samar M

    2017-02-01

    Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as

  7. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

    LENUS (Irish Health Repository)

    Doherty, Glen A

    2009-02-01

    COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.

  8. Revision history aware repositories of computational models of biological systems

    Directory of Open Access Journals (Sweden)

    Nickerson David P

    2011-01-01

    Full Text Available Abstract Background Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. Results We have extended the Physiome Model

  9. Chemopreventive effects of Cuminum cyminum in chemically induced forestomach and uterine cervix tumors in murine model systems.

    Science.gov (United States)

    Gagandeep; Dhanalakshmi, Sivanandhan; Méndiz, Ester; Rao, Agra Ramesha; Kale, Raosaheb Kathalupant

    2003-01-01

    Lately, a strong correlation has been established between diet and cancer. For ages, cumin has been a part of the diet. It is a popular spice regularly used as a flavoring agent in a number of ethnic cousins. In the present study, cancer chemopreventive potentials of different doses of a cumin seed-mixed diet were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholanthrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumor burden (tumors per mouse) by cumin. Tumor burden was 7.33 +/- 2.10 in the B(a)P-treated control group, whereas it reduced to 3.10 +/- 0.57 (P < 0.001) by a 2.5% dose and 3.11 +/- 0.60 (P <0.001) by a 5% dose of cumin seeds. Cervical carcinoma incidence, compared with the MCA-treated control group (66.67%), reduced to 27.27% (P < 0.05) by a diet of 5% cumin seeds and to 12.50% (P < 0.05) by a diet of 7.5% cumin seeds. The effect of 2.5 and 5% cumin seed-mixed diets was also examined on carcinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH), and lipid peroxidation in the liver of Swiss albino mice. Levels of cytochrome P-450 (cyt P-450) and cytochrome b5 (cyt b(5)) were significantly augmented (P < 0.05) by the 2.5% dose of cumin seed diet. The levels of cyt P-450 reductase and cyt b(5) reductase were increased (significance level being from P < 0.05 to P < 0.01) by both doses of cumin. Among the phase II enzymes, glutathione S-transferase specific activity increased (P < 0.005) by the 5% dose, whereas that of DT-diaphorase increased significantly (P < 0.05) by both doses used (2.5 and 5%). In the antioxidant system, significant elevation of the specific activities of superoxide dismutase (P < 0.01) and catalase (P < 0.05) was observed with the 5% dose of cumin. The activities of glutathione peroxidase and glutathione reductase remained unaltered by both doses of cumin. The level

  10. A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    Science.gov (United States)

    2006-02-01

    479.76 583.65 425.47 448.57 n 127 43 42 42 f) Determination of each subiect’s baseline history of smoking, diet and tea intake, plasma catechins ...AD Award Number: DAMD17-03-1-0053 TITLE: A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress...2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking- 5b. GRANT NUMBER Related

  11. Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention

    DEFF Research Database (Denmark)

    Tine, Roger Ck; Ndiaye, Pascal; Ndour, Cheikh T;

    2013-01-01

    Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken...... to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs).......Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken...

  12. National Geoscience Data Repository System, Phase III: Implementation and Operation of the Repository

    Energy Technology Data Exchange (ETDEWEB)

    American Geological Institute

    1999-05-14

    The NGDRS steering committee met at Chevron's office on March 2, 1999 in Houston, Texas to review and discuss issues of data transfer and the future of the Stapleton prospect for establishment of a national core repository. Company representatives reaffirmed their commitment in principal to the NGDRS project. Given the downturn in oil prices and final results from the due diligence of the Stapleton property, AGI has decided to forego pursuing acquisition and build-out of the Stapleton Airport property. The major petroleum companies indicated that rising the $10-12 million endowment would be difficult in the current climate. The completion of the due diligence of the property also revealed major concerns about the environmental liability associated with the property, which would require indemnification of the AGI by the City of Denver. Given these complicating results, AGI officially terminated efforts regarding the Stapleton property effective March 31, 1999. Several steering committee members put forth a proposal that the companies make their non-proprietary holdings public and list them in the NGDRS GeoTrek metadata catalog. Most of these holdings are at C&M Storage in Schulemburg, Texas. The companies are discussing methods to allow for public access to these data with C&M.

  13. A Miniature Data Repository on a Raspberry Pi

    NARCIS (Netherlands)

    Samourkasidis, Argyrios; Athanasiadis, Ioannis N.

    2017-01-01

    This work demonstrates a low-cost, miniature data repository proof-of-concept. Such a system needs to be resilient to power and network failures, and expose adequate processing power for persistent, long-term storage. Additional services are required for interoperable data sharing and visualization.

  14. /facet: A Browser for Heterogeneous Semantic Web Repositories

    NARCIS (Netherlands)

    Hildebrand, M.; Ossenbruggen, J.R. van; Hardman, L.

    2006-01-01

    Facet browsing has become popular as a user friendly interface to data repositories. The Semantic Web raises new challenges due to the heterogeneous character of the data. First, users should be able to select and navigate through facets of resources of any type and to make selections based on prope

  15. /facet: A browser for heterogeneous semantic web repositories

    NARCIS (Netherlands)

    Hildebrand, M.; Ossenbruggen, J.R. van; Hardman, L.

    2006-01-01

    Facet browsing has become popular as a user friendly interface to data repositories. We extend facet browsing of Semantic Web data in four ways. First, users are able to select and navigate through facets of resources of any type and to make selections based on properties of other, semantically rela

  16. INSTITUTIONAL REPOSITORY FOR ACCOUNTING RESEARCH RESULTS (PART 1

    Directory of Open Access Journals (Sweden)

    Volkova L. M.

    2014-03-01

    Full Text Available Increasing of the number of consumers using the advancements in technology search and delivery of scientific information, creates a need for institutional repositories that manage, preserve and maintain digital assets and intellectual products, as well as multiply the speed and convenience of obtaining the necessary information

  17. Understanding Faculty to Improve Content Recruitment for Institutional Repositories

    Science.gov (United States)

    Foster, Nancy Fried.; Gibbons, Susan

    2005-01-01

    Institutional repositories (IRs) offer many clear benefits yet faculty authors have not demonstrated much interest in depositing their content into them. Without the content, IRs will not succeed, because institutions will sustain IRs for only so long without evidence of success. A yearlong study of faculty members at the University of Rochester…

  18. Institutional Repositories at Small Institutions in America: Some Current Trends

    Science.gov (United States)

    Nykanen, Melissa

    2011-01-01

    The research reported in this article was undertaken to determine the level of implementation of institutional repositories (IRs) at small institutions enrolling fewer than 10,000 students. The study analyzed quantitative and qualitative data from IRs at a number of small institutions with the aim of observing relevant patterns and trends that may…

  19. Institutional Repositories: The Experience of Master's and Baccalaureate Institutions

    Science.gov (United States)

    Markey, Karen; St. Jean, Beth; Soo, Young Rieh; Yakel, Elizabeth; Kim, Jihyun

    2008-01-01

    In 2006, MIRACLE Project investigators censused library directors at all U.S. academic institutions about their activities planning, pilot testing, and implementing the institutional repositories on their campuses. Out of 446 respondents, 289 (64.8 percent) were from master's and baccalaureate institutions (M&BIs) where few operational…

  20. Assessment of Self-Archiving in Institutional Repositories: Across Disciplines

    Science.gov (United States)

    Xia, Jingfeng

    2007-01-01

    This research examined self-archiving practices by four disciplines in seven institutional repositories. By checking each individual item for its metadata and deposition status, the research found that a disciplinary culture is not obviously presented. Rather, self-archiving is regulated by a liaison system and a mandate policy.

  1. Evaluation of storage mechanisms for a content repository

    NARCIS (Netherlands)

    Beekman, C.G.M.

    2011-01-01

    In this thesis, we describe and evaluate different storage mechanisms for the content repository powering a content platform. In certain usage scenarios the current RDBMS-based implementation exhibits severe performance degradation. The evaluation will focus on performance and implementation complex

  2. Environmental assessment: Reference repository location, Hanford site, Washington

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1986-05-01

    In February 1983, the US Department of Energy (DOE) identified a reference repository location at the Hanford Site in Washington as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. The site is in the Columbia Plateau, which is one of five distinct geohydrologic settings considered for the first repository. To determine their suitability, the Hanford site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EAs. On the basis of the evaluations reported in this EA, the DOE has found that the Hanford site is not disqualified under the guidelines. The DOE has also found that is is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Hanford site as one of five sites available for characterization.

  3. Indian Institutional Repositories: A Study of User's Perspective

    Science.gov (United States)

    Sawant, Sarika

    2012-01-01

    Purpose: The present study aims to investigate the experience, contribution and opinions of users of respective institutional repositories (IRs) developed in India. Design/methodology/approach: The survey method was used. The data collection tool was a web questionnaire, which was created with the help of software provided by surveymonkey.com…

  4. User Oriented Platform for Data Analytics in Medical Imaging Repositories.

    Science.gov (United States)

    Valerio, Miguel; Godinho, Tiago Marques; Costa, Carlos

    2016-01-01

    The production of medical imaging studies and associated data has been growing in the last decades. Their primary use is to support medical diagnosis and treatment processes. However, the secondary use of the tremendous amount of stored data is generally more limited. Nowadays, medical imaging repositories have turned into rich databanks holding not only the images themselves, but also a wide range of metadata related to the medical practice. Exploring these repositories through data analysis and business intelligence techniques has the potential of increasing the efficiency and quality of the medical practice. Nevertheless, the continuous production of tremendous amounts of data makes their analysis difficult by conventional approaches. This article proposes a novel automated methodology to derive knowledge from medical imaging repositories that does not disrupt the regular medical practice. Our method is able to apply statistical analysis and business intelligence techniques directly on top of live institutional repositories. It is a Web-based solution that provides extensive dashboard capabilities, including complete charting and reporting options, combined with data mining components. Moreover, it enables the operator to set a wide multitude of query parameters and operators through the use of an intuitive graphical interface.

  5. Environmental effects on corrosion in the Tuff repository

    Energy Technology Data Exchange (ETDEWEB)

    Beavers, J.A.; Thompson, N.G. [Cortest Columbus, Inc., OH (USA)

    1990-02-01

    Cortest Columbus is investigating the long-term performance of container materials used for high-level waste packages as part of the information needed by the Nuclear Regulatory Commission to assess the Department of Energy`s application to construct a geologic repository for high-level radioactive waste. The scope of work consists of employing short-term techniques, to examine a wide range of possible failure modes. Long-term tests are being used to verify and further examine specific failure modes identified as important by the short-term studies. The original focus of the program was on the salt repository but the emphasis was shifted to the Tuff repository. This report summarizes the results of a literature survey performed under Task 1 of the program. The survey focuses on the influence of environmental variables on the corrosion behavior of candidate container materials for the Tuff repository. Environmental variables considered include: radiation, thermal and microbial effects. 80 refs., 44 figs., 44 tabs.

  6. Preservation Health Check: Monitoring Threats to Digital Repository Content

    Science.gov (United States)

    Kool, Wouter; van der Werf, Titia; Lavoie, Brian

    2014-01-01

    The Preservation Health Check (PHC) project, undertaken as a joint effort by Open Planets Foundation (OPF) and OCLC Research, aims to evaluate the usefulness of the preservation metadata created and maintained by operational repositories for assessing basic preservation properties. The PHC project seeks to develop an implementable logic to support…

  7. Test case for a near-surface repository

    Energy Technology Data Exchange (ETDEWEB)

    Elert, M.; Jones, C. [Kemakta Konsult AB, Stockholm (Sweden); Nilsson, L.B. [Swedish Nuclear Fuel and Waste Co, Stockholm (Sweden); Skagius, K.; Wiborgh, M. [Kemakta Konsult AB, Stockholm (Sweden)

    1998-09-01

    A test case is presented for assessment of a near-surface disposal facility for radioactive waste. The case includes waste characterization and repository design, requirements and constraints in an assessment context, scenario development, model description and test calculations 6 refs, 12 tabs, 16 figs

  8. Digital Repository for Life-long Competence Development

    NARCIS (Netherlands)

    Grigorov, Alexander; Georgiev, Atanas; Petrov, Milen; Stefanov, Krassen

    2009-01-01

    Grigorov, A., Georgiev, A., Petrov, M., & Stefanov, K. (2009). Digital Repository for Life-long Competence Development. Paper presented at the 'Open workshop of TENCompetence - Rethinking Learning and Employment at a Time of Economic Uncertainty-event'. November, 19-20, 2009, Manchester, UK: TENComp

  9. Motivations of Faculty Self-Archiving in Institutional Repositories

    Science.gov (United States)

    Kim, Jihyun

    2011-01-01

    Professors contribute to Institutional Repositories (IRs) to make their materials widely accessible in keeping with the benefits of Open Access. However, universities' commitment to IRs depends on building trust with faculty and solving copyright concerns. Digital preservation and copyright management in IRs should be strengthened to increase…

  10. Environmental assessment: Reference repository location, Hanford site, Washington

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1986-05-01

    In February 1983, the US Department of Energy (DOE) identified a reference repository location at the Hanford Site in Washington as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. The site is in the Columbia Plateau, which is one of five distinct geohydrologic settings considered for the first repository. To determine their suitability, the Hanford Site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EAs. On the basis of the evaluations reported in this EA, the DOE has found that the Hanford site is not disqualified under the guidelines. The DOE has also found that it is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Hanford site as one of five sites suitable for characterization.

  11. Usability Evaluation of a Research Repository and Collaboration Web Site

    Science.gov (United States)

    Zhang, Tao; Maron, Deborah J.; Charles, Christopher C.

    2013-01-01

    This article reports results from an empirical usability evaluation of Human-Animal Bond Research Initiative Central as part of the effort to develop an open access research repository and collaboration platform for human-animal bond researchers. By repurposing and altering key features of the original HUBzero system, Human-Animal Bond Research…

  12. Modeling transient heat transfer in nuclear waste repositories.

    Science.gov (United States)

    Yang, Shaw-Yang; Yeh, Hund-Der

    2009-09-30

    The heat of high-level nuclear waste may be generated and released from a canister at final disposal sites. The waste heat may affect the engineering properties of waste canisters, buffers, and backfill material in the emplacement tunnel and the host rock. This study addresses the problem of the heat generated from the waste canister and analyzes the heat distribution between the buffer and the host rock, which is considered as a radial two-layer heat flux problem. A conceptual model is first constructed for the heat conduction in a nuclear waste repository and then mathematical equations are formulated for modeling heat flow distribution at repository sites. The Laplace transforms are employed to develop a solution for the temperature distributions in the buffer and the host rock in the Laplace domain, which is numerically inverted to the time-domain solution using the modified Crump method. The transient temperature distributions for both the single- and multi-borehole cases are simulated in the hypothetical geological repositories of nuclear waste. The results show that the temperature distributions in the thermal field are significantly affected by the decay heat of the waste canister, the thermal properties of the buffer and the host rock, the disposal spacing, and the thickness of the host rock at a nuclear waste repository.

  13. An approach to improve Romanian geological repository planning

    Energy Technology Data Exchange (ETDEWEB)

    Andrei, Veronica [Romanian Association for Nuclear Energy, Bucharest-Magurele (Romania); Prisecaru, Ilie [University Politehnica of Bucharest, Bucharest (Romania)

    2016-04-15

    International standards recommend typical phases to be included within any national program for the development of a geological repository dedicated to disposal of the high level radioactive wastes generated in countries using nuclear power. However, these are not universally applicable and the content of each of these phases may need to be adapted for each national situation and regulatory and institutional framework. Several national geological repository programs have faced failures in schedules and have revised their programs to consider an adapted phased management approach. The authors have observed that in the case of those countries in the early phases of a geological repository program where boundary conditions have not been fully defined, international recommendations for handling delays/failures in the national program might not immediately help. This paper considers a case study of the influences of the national context risks on the current planning schedule of the Romanian national geological repository. It proposes an optimum solution for an integrated response to any significant adverse impact arising from these risks, enabling sustainable program planning.

  14. Performance assessment implementation plan for the geologic repository program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-01-01

    Performance assessment is a major constituent of the program being conducted in the Civilian Radioactive Waste Management (CRWM) Program of the US Department of Energy (DOE) to develop a geologic repository. Performance assessment is the set of activities needed for quantitative evaluations of repository-system performance to access compliance with regulations and to support the development of the geologic repository. To define the strategy for these evaluations, the DOE has developed this performance assessment strategy plan. This document discusses the need for such a strategy, the objectives and scope of the strategy plan, the relationship of the plan to other program plans. Additionally, it defines performance assessment and describes the roles of performance assessment in this program, discusses concepts and general strategies needed for performance assessment, outlines the content of the Safety Analysis Report, summarizes the requirements for the repository Environmental Impact Statement, discusses the requirements that apply to the site-suitability analyses and describes the site characterization. 10 figs., 7 tabs.

  15. Malaysian Education Index (MEI): An Online Indexing and Repository System

    Science.gov (United States)

    Kabilan, Muhammad Kamarul; Ismail, Hairul Nizam; Yaakub, Rohizani; Yusof, Najeemah Mohd; Idros, Sharifah Noraidah Syed; Umar, Irfan Naufal; Arshad, Muhammad Rafie Mohd.; Idrus, Rosnah; Rahman, Habsah Abdul

    2010-01-01

    This "Project Sheet" describes an on-going project that is being carried out by a group of educational researchers, computer science researchers and librarians from Universiti Sains Malaysia, Penang. The Malaysian Education Index (MEI) has two main functions--(1) Online Indexing System, and (2) Online Repository System. In this brief…

  16. Site suitability criteria for solidified high level waste repositories

    Energy Technology Data Exchange (ETDEWEB)

    Heckman, R.A.; Holdsworth, T.; Towse, D.F.

    1979-03-07

    Activities devoted to development of regulations, criteria, and standards for storage of solidified high-level radioactive wastes are reported. The work is summarized in sections on site suitability regulations, risk calculations, geological models, aquifer models, human usage model, climatology model, and repository characteristics. Proposed additional analytical work is also summarized. (JRD)

  17. Assessing the Quality of a Student-Generated Question Repository

    Science.gov (United States)

    Bates, Simon P.; Galloway, Ross K.; Riise, Jonathan; Homer, Danny

    2014-01-01

    We present results from a study that categorizes and assesses the quality of questions and explanations authored by students in question repositories produced as part of the summative assessment in introductory physics courses over two academic sessions. Mapping question quality onto the levels in the cognitive domain of Bloom's taxonomy, we find…

  18. ERM Ideas and Innovations: Digital Repository Management as ERM

    Science.gov (United States)

    Pinkas, María M.; Lin, Na

    2014-01-01

    This article describes the application of electronic resources management (ERM) to digital repository management at the Health Sciences and Human Services Library at the University of Maryland, Baltimore. The authors discuss electronic resources management techniques, through the application of "Techniques for Electronic Management,"…

  19. Viability assessment of a repository at Yucca Mountain: Overview

    Energy Technology Data Exchange (ETDEWEB)

    none,

    1998-12-01

    Based on the viability assessment, DOE believes that Yucca Mountain remains a promising site for a geologic repository and that work should proceed to support a decision in 2001 on whether to recommend the site to the President for development as a repository. Over 15 years, extensive research has validated many of the expectations of the scientists who first suggested that remote, desert regions of the Southwest are well-suited for a geologic repository. Engineered barriers can be designed to contain waste for thousands of years, and the natural barriers can delay and dilute any radioactive material that migrates from the waste packages. Current models indicate that the possible radiation exposure to future populations living nearby could be comparable to present-day exposure levels from natural background radiation. Design alternatives that may improve performance and reduce remaining uncertainties are now being evaluated. The performance of a geologic repository over such long time periods--longer than recorded human history--cannot be proven beyond all doubt. Forecasts about future geologic and climatic conditions and engineering estimates of how long the waste packages will remain intact cannot be directly validated. The mathematical models used in the performance assessment are subject to uncertainties that can be reduced but never completely eliminated. The Nuclear Regulatory Commission's general standard for meeting geologic repository regulatory criteria and objectives is reasonable assurance. While considerable uncertainties remain today, DOE believes that reasonable assurance should be achievable in the licensing process after the planned work is completed. The DOE believes, therefore, that ongoing work at Yucca Mountain should proceed as planned.

  20. Nevada potential repository preliminary transportation strategy Study 2. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    The objectives of this study were to build on the findings of the Nevada Potential Repository Preliminary Transportation Strategy Study 1 (CRWMS M&O 1995b), and to provide additional information for input to the repository environmental impact statement (EIS) process. In addition, this study supported the future selection of a preferred rail corridor and/or heavy haul route based on defensible data, methods, and analyses. Study research did not consider proposed legislation. Planning was conducted according to the Civilian Radioactive Waste Management Program Plan (DOE 1994a). The specific objectives of Study 2 were to: eliminate or reduce data gaps, inconsistencies, and uncertainties, and strengthen the analysis performed in Study 1; develop a preliminary list of rail route evaluation criteria that could be used to solicit input from stakeholders during scoping meetings. The evaluation criteria will be revised based on comments received during scoping; restrict and refine the width of the four rail corridors identified in Study 1 to five miles or less, based on land use constraints and engineering criteria identified and established in Study 2; evaluate national-level effects of routing spent nuclear fuel and high-level waste to the four identified branch lines, including the effects of routing through or avoiding Las Vegas; continue to gather published land use information and environmental data to support the repository EIS; continue to evaluate heavy haul truck transport over three existing routes as an alternative to rail and provide sufficient information to support the repository EIS process; and evaluate secondary uses for rail (passenger use, repository construction, shared use).

  1. [Structure, use, and risks of biomaterial repositories of embryonal tumors].

    Science.gov (United States)

    Ernestus, K; Pietsch, T; Gessler, M; Simon, T; Hero, B; Berthold, F

    2006-01-01

    Availability of statistically sufficient numbers of tumor samples and other biomaterials in high quality together with corresponding clinical data is crucial for biomedical research. Tumor repositories from individual scientists are mostly not sufficient to satisfy these criteria, especially since pediatric tumors are rare. In 2000 three centralized tumor repositories (neuroblastoma in Cologne, nephroblastoma in Würzburg, hepatoblastoma, brain tumors in Bonn) have been established by the "German Competence Net Pediatric Oncology und Hematology". The aim was to collect biomaterial including tumor samples, normal tissue, and blood in high quality for research and diagnostic purposes at a central institution. Informed consent of the parents or patients is a prerequisite for scientific use of the samples and is requested by the therapy trial. The samples are collected according to accepted standards and shipped in the specially designed Tumorbox. The tumor repository organizes the distribution of the samples to the cooperating diagnostic laboratories. The number of collected tumor samples has increased over the years. In 2000, samples from 200 patients were collected while the patient number increased to 321 in 2005. Over the years the tumor repositories collected more than 7,150 samples (fresh frozen tumor, fresh frozen normal tissue, and blood). Through links with clinical trial databases the samples can be connected with clinical data. 12 of 14 applications for tumor material to be used in specific scientific projects have been approved by an independent supervisory board. The establishment of central tumor repositories represents a major step for biomedical research activities and quality control in pediatric oncology.

  2. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study.

    Science.gov (United States)

    Shakeel, Faiyaz; Haq, Nazrul; Al-Dhfyan, Abdullah; Alanazi, Fars K; Alsarra, Ibrahim A

    2015-01-01

    Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.

  3. Cancer chemoprevention activity of labdane diterpenes from rhizomes of Hedychium coronarium

    Directory of Open Access Journals (Sweden)

    Denise C. Endringer

    2014-08-01

    Full Text Available Hedychium coronarium J. Koenig, Zingiberaceae, is a medicinal plant popularly used to treat inflammatory conditions in different countries. Three labdane diterpenes [isocoronarin D (1, methoxycoronarin D (2, ethoxycoronarin D (3] and benzoyl eugenol (4 were isolated from rhizomes and their chemopreventive potential was evaluated using in vitro assays, namely the inhibition of NF-κB, COX-1 and -2, the induction of antioxidant response element (ARE, and the inhibition of cell proliferation. Diterpene 1 activated ARE (EC50 57.6 ± 2.4 µM, while 2, 3 and 4 significantly inhibited NF-κB (IC50 of 7.3 ± 0.3, 3.2 ± 0.3 and 32.5 ± 4.9 µM, respectively. In addition, 2 and 3 selectively inhibited COX-1 (IC50 values of 0.9 ± 0.0 and 3.8 ± 0.0 µM, respectively. These data support the potential chemopreventive activity of constituents from H. coronarium rhizomes.

  4. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    Science.gov (United States)

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

  5. In Vitro Chemopreventive Properties of Green Tea, Rooibos and Honeybush Extracts in Skin Cells

    Directory of Open Access Journals (Sweden)

    Tandeka U. Magcwebeba

    2016-11-01

    Full Text Available The chemopreventive properties of the herbal teas rooibos (Aspalathus linearis and honeybush (Cyclopia spp. have been demonstrated on mouse skin in vivo but the underlying mechanisms are not clear. The aim of the current study was to determine the anti-proliferative and pro-apoptotic activity of methanol and aqueous extracts of rooibos and two Cyclopia species in different skin cells, using green tea (Camellia sinensis as a benchmark. Extracts were also characterised for their major individual polyphenols by high performance liquid chromatography and spectroscopically for the total polyphenol (TP groups. The methanol extract of rooibos, containing higher levels of polyphenols than its aqueous extract, displayed similar activity to green tea as it selectively targeted premalignant cells by inhibiting cell proliferation at lower concentrations whilst inducing apoptosis via membrane depolarisation at higher concentrations. Specific roles of the major rooibos dihydrochalcones and flavanol/proanthocyanidin-type (FLAVA compounds are likely to be involved. The aqueous extracts of the Cyclopia species were more active against cell proliferation and at inducing apoptosis which was associated with a higher FLAVA content and a reduced TP/FLAVA ratio. In contrast, their methanol extracts exhibited a cytoprotective effect against apoptosis which was related to their monomeric xanthone and flavanone content. The underlying chemopreventive properties of green tea and the herbal teas appear to be associated with diverse and complex monomeric/polymeric polyphenolic cell interactions.

  6. 10 CFR 60.131 - General design criteria for the geologic repository operations area.

    Science.gov (United States)

    2010-01-01

    ... Repository Operations Area § 60.131 General design criteria for the geologic repository operations area. (a... 10 Energy 2 2010-01-01 2010-01-01 false General design criteria for the geologic repository operations area. 60.131 Section 60.131 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF...

  7. [Uricosuric agent].

    Science.gov (United States)

    Ohno, Iwao

    2008-04-01

    Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.

  8. The Effect of Cancer Chemopreventive Agents on DNA Adduct Formation by the Dietary Prostate Carcinogen PhIP

    Science.gov (United States)

    2001-04-01

    lycopene (Hoffman meat cooked at high temperatures , may be a risk factor for colon and prostate cancers. roviding 161 mg lycopene /kg diet) as well as diet...tomato powder 2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine formed in diet providing 13 mg lycopene /kg diet) or...rats, but its utility in humans needs icer. We concluded that the consumption of lycopene beadlets, further study. Conducted under auspices of US DOE

  9. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis.

    Science.gov (United States)

    Chaudhary, Sandeep C; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A; Kopelovich, Levy; Athar, Mohammad

    2013-05-01

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (psulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial-mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways.

  10. Growing location has a pronounced effect on the accumulation of cancer chemopreventive agent Bowman-Birk inhibitor in soybean seeds

    Science.gov (United States)

    Soybeans contain several health promoting compounds including phytosterols, isoflavones, phytic acid, and protease inhibitors. The two abundant protease inhibitors of soybean seeds are the Kunitz trypsin inhibitor and the Bowman-Birk inhibitor (BBI). BBI is a serine protease inhibitor that can inhi...

  11. Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.

    Science.gov (United States)

    Chilampalli, Chandeshwari; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Chandrasekher, Gudiseva; Fahmy, Hesham; Dwivedi, Chandradhar

    2011-11-01

    Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 μmol/L concentration induced G0/G1 cell cycle arrest significantly (P Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis.

  12. Evolution of near-field physico-chemical characteristics of the SFR repository

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D. [Quintessa Ltd., Nottingham (United Kingdom); Stenhouse, M. [Monitor Scientific LLC, Denver, CO (United States); Benbow, S. [Quintessa Ltd., Henley-on-Thames (United Kingdom)

    2000-08-01

    The evaluation of the post-closure performance of the SFR repository needs to consider time dependent evolution of the repository environment. Time-dependent reaction of near-field barriers (cement, steel, bentonite) with saturating groundwater will lead to the development of hyper alkaline repository pore fluids, chemically reducing conditions, and ultimately, the generation of gas through anaerobic corrosion of metals. Cement and concrete will act as chemical conditioning agents to minimise metal corrosion and ultimately, maximise radioelement sorption. The chemical and physical evolution of cement and concrete through reaction with ambient groundwater will thus affect sorption processes through changes in pH, complexing ligands, and solid surface properties. It is desirable that these changes be incorporated into the safety assessment. The sorption behaviour of radionuclides in cementitious systems has been reviewed in detail. The available evidence from experimental work carried out on the influence of organic materials on the sorption behaviour of radionuclides, indicates that most organic degradation products will not affect sorption significantly at the concentrations expected in a cementitious repository. The notable exception to this conclusion involves the degradation products of cellulose and, in particular, polycarboxylic acids represented by iso-saccharinic acid (ISA). Results using ISA indicate a significant reduction in sorption of Pu, by several orders of magnitude, for an ISA concentration of about 10{sup -3} M. More recent data indicate that the negative effect is not as great, though still significant. Therefore, some scoping calculations are advisable to determine how realistic an ISA concentration of about 10{sup -3} M would be for the SFR repository and to estimate concentrations of other relevant organic compounds, in particular EDTA, for comparison. Scoping calculations relevant to the longevity of hyper alkaline pore fluid conditions at SFR

  13. Principal organic materials in a repository for spent nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Hallbeck, Lotta (Microbial Analytics Sweden AB, Moelnlycke (Sweden))

    2010-01-15

    The largest pool of organic material in a repository at closure is the organic material in the bentonite in buffer and backfill. It is impossible to make any assumptions as to how much of this material will be available for biodegradation, since the character of the material is unknown. However, it is unlikely that this organic material can dissolve in groundwater unless the bentonite loses its swelling capacity. The second largest pool will be the biofilms formed on the rock surfaces. This assumption presupposes that no cleaning is undertaken before repository closure. The third largest pool is the organic material produced by microorganisms using hydrogen from the anaerobic corrosion of iron in steel as an energy source. The following provides summary descriptions of the different pools of organic material that will remain in the repository: 1. Microorganisms. Their effect would mainly be to reduce the redox potential soon after repository closure. They may contribute to the depletion of the oxygen entrapped during repository construction, an effect that would not jeopardise repository stability. If the dominant microorganisms in the anaerobic environment are sulphate-reducing bacteria, oxidation of organic material would lead to the formation of HS-. The produced sulphide could corrode the copper canisters under anaerobic conditions if it reaches them. Another effect of microorganisms would be to increase the complexing capacity of the groundwater due to excreted metabolites. The impact of these compounds is not yet clear, although it will surely not be very important, due to the small amounts of such substances. 2. Materials in the ventilation air. Their effect will probably be to help maintain reducing conditions in the area, although this effect will likely be minimal or negligible. 3. Construction materials. Among these materials, we emphasise the organic materials present in concrete, asphalt, bentonite, and wood. Hydrocarbons from asphalt may help reduce

  14. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  15. Vasoactive Agents

    OpenAIRE

    Husedzinovic, Ino; Bradic, Nikola; Goranovic, Tanja

    2006-01-01

    This article is a short review of vasoactive drugs which are in use in todays clinical practice. In the past century, development of vasoactive drugs went through several phases. All of these drugs are today divided into several groups, depending on their place of action, pharmacological pathways and/or effects on target organ or organ system. Hence, many different agents are today in clinical practice, we have shown comparison between them. These agents provide new directions in the treatmen...

  16. Chemoprevention activity of 25-hydroxyvitamin D in the MMTV-PyMT mouse model of breast cancer

    Science.gov (United States)

    Development of oncologic conditions is often linked to inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Current effective vitamin D analogs including the naturally occurring active metabol...

  17. Data Publication: The Role of Community-Based, Disciplinary Repositories

    Science.gov (United States)

    Lehnert, Kerstin; Hsu, Leslie

    2013-04-01

    Data publication is increasingly recognized as a new paradigm to achieve broad and open access to data for their re-use while ensuring proper citation and attribution of the data to their creator. Current models of data publication include special data journals, institutional repositories, and programmatic or disciplinary repositories. This presentation focuses on the critical role that community-based disciplinary repositories should play, using the example of the IEDA data facility (www.iedadata.org). Disciplinary repositories ensure that data publication is successfully implemented and adopted by the science community, so that it can fulfill its promise to advance data reuse, enhance reproducibility of scientific results, and offer new opportunities for scientific discoveries. Disciplinary repositories are ideally poised to address the challenges that can lead to 'data reuse failure' (Rees 2010), which in turn obstruct the successful development and implementation of new data infrastructures for the sciences. Among these challenges are: professional motivation for investigators to publish the data; effort and economic burden of publication; discovery and long-term accessibility of data; adequate documentation of data provenance (measured parameters, uncertainty, reproducibility, materials, methods, data manipulation); and usability (file formats, interfaces to software tools for data analysis, visualization, modeling). The relevant function of a disciplinary repository is to coordinate and bridge the needs of its community with recognized requirements for data curation and demands of evolving technologies. IEDA meets that function, gathering regular guidance from the community, developing community-approved best practices and guidelines; providing guidance and tools to investigators that facilitate the process of data publication; and performing data quality control. IEDA's sustainable infrastructure supports the discovery and access of the data, and IEDA

  18. [Inotropic agents].

    Science.gov (United States)

    Sasayama, Shigetake

    2003-05-01

    Depression of myocardial contractility plays an important role in the development of heart failure and many inotropic agents were developed to improve the contractile function of the failing heart. Agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exerted dramatic short-term hemodynamic benefits, but these acute effects were not extrapolated into long-term improvement of the clinical outcome of heart failure patients. Administration of these agents to an energy starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, however, the recent large scale clinical trial has ironically proved that digoxin reduced the rate of hospitalization both overall and for worsening heart failure. More recently, attention was paid to other inotropic agents that have a complex and diversified mechanism. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including cytokine inhibitors, immunomodulators, or calcium sensitizers. In the Western Societies these agents were again shown to increase mortality of patients with severe heart failure in a dose dependent manner with the long-term administration. However, it may not be the case in the Japanese population in whom mortality is relatively low. Chronic treatment with inotropic agent may be justified in Japanese, as it allows optimal care in the context of relief of symptoms and an improved quality of life. Therefore, each racial group should obtain specific evidence aimed at developing its own guidelines for therapy rather than translating major guidelines developed for other populations.

  19. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    Science.gov (United States)

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans.

  20. A Miniature Data Repository on a Raspberry Pi

    Directory of Open Access Journals (Sweden)

    Argyrios Samourkasidis

    2016-12-01

    Full Text Available This work demonstrates a low-cost, miniature data repository proof-of-concept. Such a system needs to be resilient to power and network failures, and expose adequate processing power for persistent, long-term storage. Additional services are required for interoperable data sharing and visualization. We designed and implemented a software tool called Airchive to run on a Raspberry Pi, in order to assemble a data repository for archiving and openly sharing timeseries data. Airchive employs a relational database for storing data and implements two standards for sharing data (namely the Sensor Observation Service by the Open Geospatial Consortium and the Protocol for Metadata Harvesting by the Open Archives Initiative. The system is demonstrated in a realistic indoor air pollution data acquisition scenario in a four-month experiment evaluating its autonomy and robustness under power and network disruptions. A stress test was also conducted to evaluate its performance against concurrent client requests.

  1. Lithophysal Rock Mass Mechanical Properties of the Repository Host Horizon

    Energy Technology Data Exchange (ETDEWEB)

    D. Rigby

    2004-11-10

    The purpose of this calculation is to develop estimates of key mechanical properties for the lithophysal rock masses of the Topopah Spring Tuff (Tpt) within the repository host horizon, including their uncertainties and spatial variability. The mechanical properties to be characterized include an elastic parameter, Young's modulus, and a strength parameter, uniaxial compressive strength. Since lithophysal porosity is used as a surrogate property to develop the distributions of the mechanical properties, an estimate of the distribution of lithophysal porosity is also developed. The resulting characterizations of rock parameters are important for supporting the subsurface design, developing the preclosure safety analysis, and assessing the postclosure performance of the repository (e.g., drift degradation and modeling of rockfall impacts on engineered barrier system components).

  2. The convection cooling system of the Yakutsk permafrost seed repository

    Institute of Scientific and Technical Information of China (English)

    Vladimir N.Panin; Georgii P.Kuzmin

    2014-01-01

    Temperature is critical to maintaining seed viability under long term storage conditions. It has been common practice to use refrigeration systems to maintain required storage temperatures. A seed repository constructed in permafrost in Ya kutsk, Russia is the first seed storage facility that relies solely on natural cold. This paper describes the design and per formance of the cooling system of the repository. An innovative aspect of the cooling system is that it utilizes the patterns of temperature wave propagation in permafrost. Predicted and measured ground temperatures for the first year of operation are presented and analyzed. Results indicate that convection air cooling systems can be used to control the temperature regime in underground facilities in permafrost.

  3. The study on safety facility criteria for radioactive waste repository

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. H.; Choi, M. H.; Han, S. H. and others [Dongbang Electron Industry Corporation, (Korea, Republic of)

    1992-12-15

    The radioactive waste repository are necessary to install the engineered safety systems to secure the safety for operation of the repository in the event of fire and earthquake. Since the development of safety facility criteria requires a thorough understanding about the characteristics of the engineered safety systems, we should investigate by means of literature survey and visit SKB. In particular, definition, composition of the systems, functional requirement of the systems, engineered safety systems of foreign countries, system design, operation and maintenance requirement should be investigated : fire protection system, ventilation system, drainage system, I and C system, electric system, radiation monitoring system. This proposed criteria consist of purpose, scope of application, ventilation system, fire protection system, drainage system, electric system and this proposed criteria can be applied as a basic reference for the final criteria.

  4. Monitored Geologic Repository Operations Monitoring and Control System Description Document

    Energy Technology Data Exchange (ETDEWEB)

    E.F. Loros

    2000-06-29

    The Monitored Geologic Repository Operations Monitoring and Control System provides supervisory control, monitoring, and selected remote control of primary and secondary repository operations. Primary repository operations consist of both surface and subsurface activities relating to high-level waste receipt, preparation, and emplacement. Secondary repository operations consist of support operations for waste handling and treatment, utilities, subsurface construction, and other selected ancillary activities. Remote control of the subsurface emplacement operations, as well as, repository performance confirmation operations are the direct responsibility of the system. In addition, the system monitors parameters such as radiological data, air quality data, fire detection status, meteorological conditions, unauthorized access, and abnormal operating conditions, to ensure a safe workplace for personnel. Parameters are displayed in a real-time manner to human operators regarding surface and subsurface conditions. The system performs supervisory monitoring and control for both important to safety and non-safety systems. The system provides repository operational information, alarm capability, and human operator response messages during emergency response situations. The system also includes logic control to place equipment, systems, and utilities in a safe operational mode or complete shutdown during emergency response situations. The system initiates alarms and provides operational data to enable appropriate actions at the local level in support of emergency response, radiological protection response, evacuation, and underground rescue. The system provides data communications, data processing, managerial reports, data storage, and data analysis. This system's primary surface and subsurface operator consoles, for both supervisory and remote control activities, will be located in a Central Control Center (CCC) inside one of the surface facility buildings. The system

  5. Multinational repositories: Ethical, legal and political/public aspects

    Energy Technology Data Exchange (ETDEWEB)

    Boutellier, C. [ARiUS - Association for Regional and International Underground Storage, Tafernstrasse 11, CH-5405 Baden, Dattwil (Switzerland)]. E-mail: Christine.Boutellier@arius-world.org; McCombie, C. [ARiUS - Association for Regional and International Underground Storage, Tafernstrasse 11, CH-5405 Baden, Dattwil (Switzerland)]. E-mail: Charles.McCombie@arius-world.org; Mele, I. [ARAO - Agency for Radwaste Management, Parmova 53, SI-1000 Ljubljana (Slovenia)]. E-mail: irena.mele@gov.si

    2006-07-01

    Concepts for shared multinational repositories face a great challenge in achieving acceptance, despite the fact that they promise advantages in safety, security, environmental protection and costs. When considering advantages of shared multinational repositories, it is instructive to examine which are the ethical, legal and political issues that mostly affect the feasibility of implementing such facilities. This paper addresses the key questions from two opposite sides. The early part takes a 'top-down' view, looking at the international debate on ethical issues, summarising a wide range of national political attitudes and identifying relevant international legislation and treaties. The latter looks 'bottom-up' at the problem, by discussing the situation of a small country, Slovenia. Slovenia has limited financial resources for implementing disposal - but it has a firm commitment to fulfilling its responsibilities for safely managing all Radioactive Wastes (RAW) arising in the country. Strategies considered to do so are laid out in this paper. (author)

  6. Simulated geophysical monitoring of radioactive waste repository barriers

    Science.gov (United States)

    Biryukov, Anton

    Estimation of attenuation of the elastic waves in clays and high clay-content rocks is important for the quality of geophysical methods relying on processing the recorded waveforms. Time-lapse imaging is planned to be employed for monitoring of the condition of high-radioactive waste repositories. Engineers can analyze and optimize configuration of the monitoring system using numerical modelling tools. The reliability of modeling requires proper calibration. The purpose of this thesis is threefold: (i) propose a calibration methodology for the wave propagation tools based on the experimental data, (ii) estimate the attenuation in bentonite as a function of temperature and water content, and (iii) investigate the feasibility of active sonic monitoring of the engineered barriers. The results suggest that pronounced inelastic behavior of bentonite has to be taken into account in geophysical modeling and analysis. The repository--scale models confirm that active sonic monitoring is capable of depicting physical changes in the bentonite barrier.

  7. Cross Institutional Cooperation on a Shared Bit Repository

    DEFF Research Database (Denmark)

    Zierau, Eld; Kejser, Ulla Bøgvad

    2010-01-01

    This paper explores how independent institutions, such as archives and libraries, can cooperate on managing a shared bit repository with bit preservation in order to use their resources for preservation n in a more cost-effective way. It uses the OAIS Reference Model to provide a framework......, and confidentiality. This study further revealed that requirements for the level of bit safety must be supplemented by risk analysis, which needs to involve elements of the architecture; for example, the number of copies and how independence between the copies is ensured. The paper describes bit repository...... architecture and its strengths in being flexible in order to offer differentiated services with respect to, among other things, bit safety and cost. Furthermore, the challenges in formulating various aspects, such as risk requirements, are described....

  8. Cross Institutional Cooperation on a Shared Bit Repository

    DEFF Research Database (Denmark)

    Zierau, Eld; Kejser, Ulla Bøgvad

    2013-01-01

    This paper explores how independent institutions, such as archives and libraries, can cooperate on managing a shared bit repository with bit preservation, in order to use their resources for preservation in a more cost-effective way. It uses the OAIS Reference Model to provide a framework......, and confidentiality. This study furthermore revealed that requirements for the level of bit safety must be supplemented by risk analysis, which needs to involve elements of the architecture, e.g. the number of copies and how independence between the copies is ensured. The paper describes the bit repository...... architecture, its strengths in being flexible in order to offer differentiated services with respect to, among other things, bit safety and cost. Furthermore, the challenges in formulating e.g. risk requirements are described....

  9. The Peer Review Process: An Expanded Role for Repositories

    Directory of Open Access Journals (Sweden)

    Joanna Richardson

    2014-02-01

    Full Text Available Peer review has been regarded as a cornerstone of scientific research for a considerable time. Journals seeking to attract high quality scholarship rely on peer review to maintain their credentials in the publishing industry. However, over a period of time—and especially given the advent of the Internet—complaints have arisen from authors, reviewers and even editors as to the efficacy of the system. The authors outline a range of models which have evolved that either complement or replace evaluation processes which characterise traditional peer review. Research data is presented in the context of quality assessment. The authors introduce several approaches which are utilising repositories to support the process. Consideration is given as to how this might change the current institutional repository environment.

  10. Performance assessment modeling of the proposed Genting Island repository facility

    Energy Technology Data Exchange (ETDEWEB)

    Imardjoko, Y.U. [Gadjah Mada Univ., Yogyakarta (Indonesia); Bullen, D.B. [Iowa State Univ., Ames, IA (United States); Yatim, S. [National Atomic Energy Agency, Tangerang (Indonesia)

    1996-12-01

    Indonesia is about to enter the nuclear era with the construction of several nuclear power plants in the near future. Numerous issues, including disposal of high-level radioactive wastes, must be addressed to evaluate the impact of these plants on the environment. This paper reviews the Genting ocean island repository site development plan with respect to three main areas, the inventory of HLRW, the barrier systems (natural and engineered), and the physical condition of the site. The radionuclide inventory and waste form require analyses of the waste package that include selection of container materials, the type of engineered barrier and its predicted performance, and radionuclide release models. Parameters pertinent to the repository site includes information pertaining to the geology, hydrology, climatology, and water chemistry of the site. These data are important to aid in the prediction of the long-term performance of the site.

  11. An Open Challenge Problem Repository for Systems Supporting Binders

    Directory of Open Access Journals (Sweden)

    Amy Felty

    2015-07-01

    Full Text Available A variety of logical frameworks support the use of higher-order abstract syntax in representing formal systems; however, each system has its own set of benchmarks. Even worse, general proof assistants that provide special libraries for dealing with binders offer a very limited evaluation of such libraries, and the examples given often do not exercise and stress-test key aspects that arise in the presence of binders. In this paper we design an open repository ORBI (Open challenge problem Repository for systems supporting reasoning with BInders. We believe the field of reasoning about languages with binders has matured, and a common set of benchmarks provides an important basis for evaluation and qualitative comparison of different systems and libraries that support binders, and it will help to advance the field.

  12. Implementing the EuroFIR Document and Data Repositories as accessible resources of food composition information.

    Science.gov (United States)

    Unwin, Ian; Jansen-van der Vliet, Martine; Westenbrink, Susanne; Presser, Karl; Infanger, Esther; Porubska, Janka; Roe, Mark; Finglas, Paul

    2016-02-15

    The EuroFIR Document and Data Repositories are being developed as accessible collections of source documents, including grey literature, and the food composition data reported in them. These Repositories will contain source information available to food composition database compilers when selecting their nutritional data. The Document Repository was implemented as searchable bibliographic records in the Europe PubMed Central database, which links to the documents online. The Data Repository will contain original data from source documents in the Document Repository. Testing confirmed the FoodCASE food database management system as a suitable tool for the input, documentation and quality assessment of Data Repository information. Data management requirements for the input and documentation of reported analytical results were established, including record identification and method documentation specifications. Document access and data preparation using the Repositories will provide information resources for compilers, eliminating duplicated work and supporting unambiguous referencing of data contributing to their compiled data.

  13. Sunscreening Agents

    Science.gov (United States)

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  14. A Mock-Up Tool for Software Component Reuse Repository

    OpenAIRE

    P.Niranjan; C.V.Guru Rao

    2010-01-01

    Software Reuse effectiveness can be improved by reducing cost and investment.Software reuse costs can be reduced when reusable components are easy to locate, adaptand integrate into new efficient applications. Reuse is the key paradigm for increasingsoftware quality in the software development. This paper focuses on the implementationof software tool with a new integrated classification scheme to make classification buildof software components and effective software reuse repositories to faci...

  15. E-sharing: development and use of learning objects repository

    OpenAIRE

    Gonçalves, Maria José Angélico; Pereira, Rui Humberto; Pérez Cota, Manuel

    2009-01-01

    — In the new learning environments, built width digital technologies, the need to promote quality of education resources, commonly known as Learning Objects, which can support formal and informal distance learning, emerge as one of the biggest challenge that educational institutions will have to face. Due to the fact that is expensive, the reuse and sharing became very important issue. This article presents a Learning Object Repository which aims to store, to disse...

  16. REPOSITORY LAYOUT SUPPORTING DESIGN FEATURE #13- WASTE PACKAGE SELF SHIELDING

    Energy Technology Data Exchange (ETDEWEB)

    J. Owen

    1999-04-09

    The objective of this analysis is to develop a repository layout, for Feature No. 13, that will accommodate self-shielding waste packages (WP) with an areal mass loading of 25 metric tons of uranium per acre (MTU/acre). The scope of this analysis includes determination of the number of emplacement drifts, amount of emplacement drift excavation required, and a preliminary layout for illustrative purposes.

  17. The role of natural analogs in the repository licensing process

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, W.M. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)

    1995-09-01

    The concept of a permanent geologic repository for high-level nuclear waste (NLW) is implicitly based on analogy to natural systems that have been stable for millions or billions of years. The time of radioactive and chemical toxicity of HLW exceeds the duration of human civilization, and it is impossible to demonstrate the accuracy of predictions of the behavior of engineered or social systems over such long periods.

  18. National Geoscience Data Repository System: Phase 2 final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-01

    The American Geological Institute (AGI) has completed Phase 2 of a project to establish a National Geoscience Data Repository System (NGDRS). The project`s primary objectives are to preserve geoscience data in jeopardy of being destroyed and to make that data available to those who have a need to use it in future investigations. These data are available for donation to the public as a result of the downsizing that has occurred in the major petroleum and mining companies in the US for the past decade. In recent years, these companies have consolidated domestic operations, sold many of their domestic properties and relinquished many of their leases. The scientific data associated with those properties are no longer considered to be useful assets and are consequently in danger of being lost forever. The national repository project will make many of these data available to the geoscience community for the first time. Phase 2 encompasses the establishment of standards for indexing and cataloging of geoscience data and determination of the costs of transferring data from the private sector to public-sector data repositories. Pilot projects evaluated the feasibility of the project for transfer of different data types and creation of a Web-based metadata supercatalog and browser. Also as part of the project, a national directory of geoscience data repositories was compiled to assess what data are currently available in existing facilities. The next step, Phase 3, will focus on the initiation of transfer of geoscience data from the private sector to the public domain and development of the web-based Geotrek metadata supercatalog.

  19. PRIDE: Quality control in a proteomics data repository

    OpenAIRE

    Csordas, A.; Ovelleiro, D.; Wang, R.; Foster, J. M.; Rios, D.; Vizcaino, J. A.; Hermjakob, H.

    2012-01-01

    The PRoteomics IDEntifications (PRIDE) database is a large public proteomics data repository, containing over 270 million mass spectra (by November 2011). PRIDE is an archival database, providing the proteomics data supporting specific scientific publications in a computationally accessible manner. While PRIDE faces rapid increases in data deposition size as well as number of depositions, the major challenge is to ensure a high quality of data depositions in the context of highly diverse prot...

  20. Copper corrosion under expected conditions in a deep geologic repository

    Energy Technology Data Exchange (ETDEWEB)

    King, F. [Integrity Corrosion Consulting Ltd, Calgary, Alberta (Canada); Ahonen, L. [Geological Survey of Finland, Espoo (Finland); Taxen, C. [Swedish Corrosion Inst., Stockholm (Sweden); Vuorinen, U. [VTT Chemical Technology, Espoo (Finland); Werme, L. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden)

    2001-12-01

    Copper has been the corrosion barrier of choice for the canister in the Swedish and Finnish, nuclear waste disposal programmes for over 20 years. During that time many studies have been carried out on the corrosion behaviour of copper under conditions likely to exist in an underground nuclear disposal repository located in he Fenno-Scandian bedrock. This review is a summary of what has been learnt about the long- term behaviour of the corrosion barrier during this period and what the implications of this knowledge are for the predicted service life of the canisters. The review is based on the existing knowledge from various nuclear waste management programs around the world and from the open literature.Various areas are considered: the expected evolution of the geochemical conditions in the groundwater and of the repository environment, the thermodynamics of copper corrosion, corrosion before and during saturation of the compacted bentonite buffer by groundwater, general and localized corrosion following saturation of the compacted bentonite buffer, stress corrosion cracking, radiation effects, the implications of corrosion on the service life of the canister, and areas for further study. Much has been learnt about the long-term corrosion behaviour of copper canisters over the past 20 years. The majority of the information reviewed here is drawn from the Swedish/Finnish and Canadian programmes. Despite differences in scientific approach, and canister and repository design, the results of these two programmes both suggest that copper provides an excellent corrosion barrier in an underground repository. The conclusion drawn from this review is that the original prediction made in 1978 of canister lifetimes exceeding 100,000 years remains valid.

  1. Copper corrosion under expected conditions in a deep geologic repository

    Energy Technology Data Exchange (ETDEWEB)

    King, F.; Ahonen, L.; Taxen, C.; Vuorinen, U.; Werme, L

    2002-01-01

    Copper has been the corrosion barrier of choice for the canister in the Swedish and Finnish, nuclear waste disposal programmes for over 20 years. During that time many studies have been carried out on the corrosion behaviour of copper under conditions likely to exist in an underground nuclear disposal repository located in the Fenno-Scandian bedrock. This review is a summary of what has been learnt about the long-term behaviour of the corrosion barrier during this period and what the implications of this knowledge are for the predicted service life of the canisters. The review is based on the existing knowledge from various nuclear waste management programs around the world and from the open literature. Various areas are considered: the expected evolution of the geochemical conditions in the groundwater and of the repository environment, the thermodynamics of copper corrosion, corrosion before and during saturation of the compacted bentonite buffer by groundwater, general and localized corrosion following saturation of the compacted bentonite buffer, stress corrosion cracking, radiation effects, the implications of corrosion on the service life of the canister, and areas for further study. Much has been learnt about the long-term corrosion behaviour of copper canisters over the past 20 years. The majority of the information reviewed here is drawn from the Swedish/Finnish and Canadian programmes. Despite differences in scientific approach, and canister and repository design, the results of these two programmes both suggest that copper provides an excellent corrosion barrier in an underground repository. The conclusion drawn from this review is that the original prediction made in 1978 of canister lifetimes exceeding 100,000 years remains valid. (orig.)

  2. Thermal Conductivity of the Potential Repository Horizon Model Report

    Energy Technology Data Exchange (ETDEWEB)

    J. Ramsey

    2002-08-29

    The purpose of this report is to assess the spatial variability and uncertainty of thermal conductivity in the host horizon for the proposed repository at Yucca Mountain. More specifically, the lithostratigraphic units studied are located within the Topopah Spring Tuff (Tpt) and consist of the upper lithophysal zone (Tptpul), the middle nonlithophysal zone (Tptpmn), the lower lithophysal zone (Tptpll), and the lower nonlithophysal zone (Tptpln). The Tptpul is the layer directly above the repository host layers, which consist of the Tptpmn, Tptpll, and the Tptpln. Current design plans indicate that the largest portion of the repository will be excavated in the Tptpll (Board et al. 2002 [157756]). The main distinguishing characteristic among the lithophysal and nonlithophysal units is the percentage of large scale (cm-m) voids within the rock. The Tptpul and Tptpll, as their names suggest, have a higher percentage of lithophysae than the Tptpmn and the Tptpln. Understanding the influence of the lithophysae is of great importance to understanding bulk thermal conductivity and perhaps repository system performance as well. To assess the spatial variability and uncertainty of thermal conductivity, a model is proposed that is functionally dependent on the volume fraction of lithophysae and the thermal conductivity of the matrix portion of the rock. In this model, void space characterized as lithophysae is assumed to be air-saturated under all conditions, while void space characterized as matrix may be either water- or air-saturated. Lithophysae are assumed to be air-saturated under all conditions since the units being studied are all located above the water table in the region of interest, and the relatively strong capillary forces of the matrix will, under most conditions, preferentially retain any moisture present in the rock.

  3. Integrating Software Repository Mining: A Decision Support Centered Approach

    Directory of Open Access Journals (Sweden)

    Luiz Dourado Dias Junior

    2012-12-01

    Full Text Available Mining software repositories (MSR research had significantly contributed to software engineering.However, MSR results integration across repositories is a recent concern that is getting more attentionfrom researchers each day. Some noticeable research in this sense is related to the approximation betweenMSR and semantic web, specially linked data approaches which makes it possible to integrate repositoriesand mined results. Manifested that way, we believe that current research is not fully addressing thepractical integration of MSR results, specially, in software engineering due to not considering that theseresults needs to be integrated to the tools as assistance to activity performers, as a kind of decision makingsupport. Based on this statement this research describes an approach, named Sambasore, which isconcerned with MSR results inter-repository integration and also to decision making support processes,based on tool assistance modelling. To show its feasibility we describe the main concepts, some relatedworks and also a proof of concept experiment applied to a software process modelling tool named SpiderPM.

  4. Aquatic ecosystem characterisation strategy at a repository site

    Energy Technology Data Exchange (ETDEWEB)

    Kangasniemi, Ville; Ikonen, Ari T.K. [Environmental Research and Assessment EnviroCase, Ltd., Hallituskatu 1 D 4, 28100 Pori (Finland); Lahdenperae, Anne-Maj [Saanio and Riekkola Oy, Laulukuja 4, 00420 Helsinki (Finland); Kirkkala, Teija [Pyhaejaervi Institute, Sepaentie 7, 27500 Kauttua (Finland); Koivunen, Sari [Water and Environment Research of South-West Finland, Telekatu 16, 20360 Turku (Finland)

    2014-07-01

    Olkiluoto Island on the western coast of Finland has been selected as a repository site for spent nuclear fuel disposal. According to regulatory requirements, the safety assessment for the repository should have an assessment timeframe of several millennia. Due to the post-glacial land uplift, the relatively shallow sea areas around Olkiluoto Island will change gradually to lakes, rivers and terrestrial areas. As there are no limnic systems at present Olkiluoto site, the reference area was delineated and reference lakes and rivers were selected as an analogue. For the modelling of the transport and accumulation of possible radionuclide releases in the surface environment, aquatic ecosystems were identified and divided into biotopes. Despite the number of available templates, the division of aquatic environment for the biosphere assessment of the Olkiluoto spent fuel repository was necessary to made separately. In this contribution, the processes behind the identification of aquatic ecosystems (e.g. legislation, physical and chemical properties) together with the biotope selection methodology (e.g. light and bottom conditions) and the challenges related to the amount of variable input parameters for each biotope in the modelling are presented. (authors)

  5. A proposed application programming interface for a physical volume repository

    Science.gov (United States)

    Jones, Merritt; Williams, Joel; Wrenn, Richard

    1996-01-01

    The IEEE Storage System Standards Working Group (SSSWG) has developed the Reference Model for Open Storage Systems Interconnection, Mass Storage System Reference Model Version 5. This document, provides the framework for a series of standards for application and user interfaces to open storage systems. More recently, the SSSWG has been developing Application Programming Interfaces (APIs) for the individual components defined by the model. The API for the Physical Volume Repository is the most fully developed, but work is being done on APIs for the Physical Volume Library and for the Mover also. The SSSWG meets every other month, and meetings are open to all interested parties. The Physical Volume Repository (PVR) is responsible for managing the storage of removable media cartridges and for mounting and dismounting these cartridges onto drives. This document describes a model which defines a Physical Volume Repository, and gives a brief summary of the Application Programming Interface (API) which the IEEE Storage Systems Standards Working Group (SSSWG) is proposing as the standard interface for the PVR.

  6. Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.

    Science.gov (United States)

    Karimian, Hamed; Fadaeinasab, Mehran; Zorofchian Moghadamtousi, Soheil; Hajrezaei, Maryam; Razavi, Mahboubeh; Safi, Sher Zaman; Ameen Abdulla, Mahmood; Mohd Ali, Hapipah; Ibrahim Noordin, Mohamad

    2015-01-01

    Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.

  7. Mobile Agents

    Science.gov (United States)

    Satoh, Ichiro

    Mobile agents are autonomous programs that can travel from computer to computer in a network, at times and to places of their own choosing. The state of the running program is saved, by being transmitted to the destination. The program is resumed at the destination continuing its processing with the saved state. They can provide a convenient, efficient, and robust framework for implementing distributed applications and smart environments for several reasons, including improvements to the latency and bandwidth of client-server applications and reducing vulnerability to network disconnection. In fact, mobile agents have several advantages in the development of various services in smart environments in addition to distributed applications.

  8. Cancer Chemoprevention Effects of Ginger and its Active Constituents: Potential for New Drug Discovery.

    Science.gov (United States)

    Wang, Chong-Zhi; Qi, Lian-Wen; Yuan, Chun-Su

    2015-01-01

    Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.

  9. Esophageal cancer: The latest on chemoprevention and state of the art therapies.

    Science.gov (United States)

    Le Bras, Gregoire F; Farooq, Muhammad H; Falk, Gary W; Andl, Claudia D

    2016-11-01

    Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low. As we will discuss in this review, multiple characteristics specific to the disease stage and patient must be considered when choosing a treatment plan. This article will summarize current standard therapies, potential application of chemoprevention drugs and the promise and partial failure of personalized medicine, as well as novel treatments addressing this disease.

  10. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  11. Institutional repository `eKMAIR': establishing and populating a research repository for the National University "Kyiv Mohyla Academy"

    CERN Document Server

    Yaroshenko, Tetiana

    2012-01-01

    University libraries have an increasingly important role to play in supporting open access publishing and dissemination of research outputs.1 In particular, many libraries are playing a leading role in establishing and managing institutional repositories. Institutional repositories are, most often, Open Access Initiative (OAI)-compliant databases of a university or other research institution's intellectual output, most typically research papers, although many other forms of digital media can also be stored and disseminated. Their main function is to provide improved access to the full text of research articles and improve retrieval of relevant research. The National University "Kyiv Mohyla Academy" is a small-sized institution with approximately 3,000 students and 500 academic staff. Although it is a teaching-intensive university, developing research and knowledge-transfer capacity is a strategic priority and four research institutes have been established, with further research activity going on in the academ...

  12. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling

    Science.gov (United States)

    Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

  13. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

    Directory of Open Access Journals (Sweden)

    Carina Michl

    Full Text Available Sulforaphane (SFN and moringin (GMG-ITC are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders.

  14. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

    Science.gov (United States)

    Michl, Carina; Vivarelli, Fabio; Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders.

  15. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  16. Cancer chemoprevention by phytochemicals: potential molecular targets,biomarkers and animal models

    Institute of Scientific and Technical Information of China (English)

    Ki Han KWON; Avantika BARVE; Siwang YU; Mou-Tuan HUANG; Ah-Ng Tony KONG

    2007-01-01

    Recent studies have strongly indicated that certain daily-consumed dietary phytochemicals could have cancer protective effects against transgenic mice can-cer models and cancers mediated by carcinogens, irradiations and carcinogenic metabolites derived from exogenous or endogenous sources. The cancer-protec-tive effects elicited by these dietary compounds are believed to be due at least in part to the induction of cellular defense systems including the detoxifying and antioxidant enzymes system, as well as the inhibition of anti-inflammatory and anti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death. In this review, we summarize the potential mechanisms including the modu-lation of nuclear factor kappaB (NF-κB), cyclooxygenases-2 (COX-2), activator protein-1 (AP-1), mitogen-activated protein kinases (MAPKs) and the induction of phase Ⅱ cellular detoxifying and antioxidant enzymes mediated mainly by the antioxidant response elements (ARE) within the promoter regions of these genes through nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap 'n' collar (CNC) family of the basic region-leucine zipper transcription factor. In addition, we also review several animal models of carcinogenesis and cancer chemopreventive efficacy studies of these animal models using dietary chemopreventive compounds. Finally, we discuss the cellular signaling cascades mediated by Nrf2, NF-κB, AP-1, MAPKs and COX-2, which have been considered to play pivotal roles in tumor initiation, promotion and progression processes,and could be promising molecular targets for the design of drugs targeting cancer prevention and therapy.

  17. Viability Assessment of a Repository at Yucca Mountain. Volume 5: Costs to Construct and Operate the Repository

    Energy Technology Data Exchange (ETDEWEB)

    None

    1998-12-01

    This volume presents a management summary of the cost estimate to complete the design, and to license, construct, operate, monitor, close, and decommission a Monitored Geologic Repository at Yucca Mountain in Nevada. This volume summarizes the scope, estimating methodologies, and assumptions used in development of the Monitored Geologic Repository-VA cost estimate. It identifies the key features necessary to understand the summary costs presented herein. This cost summary derives from a larger body of documented cost analysis. Volume 5 is organized to reflect this structured approach to cost estimation and contains the following sections: Section 1, Cost Elements. This section briefly defines the components of each major repository cost element. Section 2, Project Phases. This section presents the definition, as used in the estimate, of five project phases (Licensing, Pre-emplacement Construction, Emplacement Operations, Monitoring, and Closure and Decommissioning) and the schedule dates for each phase. It also contains major milestone dates and a bar chart schedule. Section 3, Major Assumptions. This section identifies key high-level assumptions for the cost estimate basis. Additional detailed assumptions are included in the appendices. Section 4, Integrated Cost Summary. This section presents a high-level roll-up of the VA costs resulting from the estimating work. The tables and figures contained in this section were compiled from the more detailed cost estimates in the appendices. Section 5, References. This section identifies the references that support this cost volume. Appendices. For each major repository cost element, Appendices B-F [B, C, D, E, F] presents additional information on the scope of cost elements, identifies methodologies used to develop the cost estimates, lists underlying cost assumptions, and tabulates summary results. Appendix A contains a glossary to assist the reader in understanding the terminology in Volume 5. Appendix G presents costs

  18. Scientific basis for a safety case of deep geological repositories

    Energy Technology Data Exchange (ETDEWEB)

    Noseck, Ulrich; Becker, Dirk-Alexander; Brasser, Thomas [and others

    2012-11-15

    Within this project strategies and methods to build a safety case for deep geological repositories are further developed. This includes also the scientific fundamentals as a basis of the safety case. In the international framework the methodology of the Safety Case is frequently applied and continuously improved. According to definitions from IAEA and NEA the Safety Case is a compilation of arguments and facts, which describe, quantify and support the safety and the degree of confidence in the safety of the geological repository. The safety of the geological repository should be demonstrated by the safety case. The safety case is the basis for essential decisions during a repository programme. It comprises the results of safety assessments in combination with additional information like multiple lines of evidence and a discussion of robustness and quality of the repository, its design and the quality of all safety assessments including the basic assumptions. A crucial element of the Safety Case is the long-term safety analysis, i.e. the systematic analysis of the hazards connected with the facility and the capability of site and repository design to ensure the required safety functions and to fulfill the technical claims. Long-term safety analysis requires a powerful and qualified programme package, which contains appropriate hardware and software as well as well trained and experienced modellers performing the model calculations. The calculation tools used within safety cases need to be checked and verified and continuously adapted to the state-of-the-art science and technology. Especially it needs to be applicable to a real repository system. For the assessment of safety a deep process understanding is necessary. The R and D work performed within this project will contribute to the improvement of process and system understanding as well as to the further development of methods and strategies applied in the safety case. Emphasis was put on the following aspects

  19. A Distributed Multi-Agent System for Collaborative Information Management and Learning

    Science.gov (United States)

    Chen, James R.; Wolfe, Shawn R.; Wragg, Stephen D.; Koga, Dennis (Technical Monitor)

    2000-01-01

    In this paper, we present DIAMS, a system of distributed, collaborative agents to help users access, manage, share and exchange information. A DIAMS personal agent helps its owner find information most relevant to current needs. It provides tools and utilities for users to manage their information repositories with dynamic organization and virtual views. Flexible hierarchical display is integrated with indexed query search-to support effective information access. Automatic indexing methods are employed to support user queries and communication between agents. Contents of a repository are kept in object-oriented storage to facilitate information sharing. Collaboration between users is aided by easy sharing utilities as well as automated information exchange. Matchmaker agents are designed to establish connections between users with similar interests and expertise. DIAMS agents provide needed services for users to share and learn information from one another on the World Wide Web.

  20. A systems pharmacokinetic and pharmacodynamic approach to identify opportunities and pitfalls in energy stress-mediated chemoprevention: the use of metformin and other biguanides.

    Science.gov (United States)

    Thompson, Matthew D; Thompson, Henry J

    2012-12-01

    Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin.

  1. Scientific basis for a safety case of deep geological repositories

    Energy Technology Data Exchange (ETDEWEB)

    Noseck, Ulrich; Becker, Dirk-Alexander; Brasser, Thomas [and others

    2012-11-15

    Within this project strategies and methods to build a safety case for deep geological repositories are further developed. This includes also the scientific fundamentals as a basis of the safety case. In the international framework the methodology of the Safety Case is frequently applied and continuously improved. According to definitions from IAEA and NEA the Safety Case is a compilation of arguments and facts, which describe, quantify and support the safety and the degree of confidence in the safety of the geological repository. The safety of the geological repository should be demonstrated by the safety case. The safety case is the basis for essential decisions during a repository programme. It comprises the results of safety assessments in combination with additional information like multiple lines of evidence and a discussion of robustness and quality of the repository, its design and the quality of all safety assessments including the basic assumptions. A crucial element of the Safety Case is the long-term safety analysis, i.e. the systematic analysis of the hazards connected with the facility and the capability of site and repository design to ensure the required safety functions and to fulfill the technical claims. Long-term safety analysis requires a powerful and qualified programme package, which contains appropriate hardware and software as well as well trained and experienced modellers performing the model calculations. The calculation tools used within safety cases need to be checked and verified and continuously adapted to the state-of-the-art science and technology. Especially it needs to be applicable to a real repository system. For the assessment of safety a deep process understanding is necessary. The R and D work performed within this project will contribute to the improvement of process and system understanding as well as to the further development of methods and strategies applied in the safety case. Emphasis was put on the following aspects

  2. Radioprotective Agents

    Science.gov (United States)

    1982-01-01

    claimed to be effective are gallic acid derivatives, eg, sodium gallate 12053-21-61 (295-297) and propyl gallate 1121-79-91 (298). p...inhibition of a-adrenergic receptors can be achieved through the use of the antiradiation agents 2-(5-aminopentylamino)ethanephos- phorothioic acid ...tissue was ap- preciated immediately as a potential medical set, and they were put to use en- thusiastically. Early workers did notice an erythematous

  3. Rolling Deck to Repository I: Designing a Database Infrastructure

    Science.gov (United States)

    Arko, R. A.; Miller, S. P.; Chandler, C. L.; Ferrini, V. L.; O'Hara, S. H.

    2008-12-01

    The NSF-supported academic research fleet collectively produces a large and diverse volume of scientific data, which are increasingly being shared across disciplines and contributed to regional and global syntheses. As both Internet connectivity and storage technology improve, it becomes practical for ships to routinely deliver data and documentation for a standard suite of underway instruments to a central shoreside repository. Routine delivery will facilitate data discovery and integration, quality assessment, cruise planning, compliance with funding agency and clearance requirements, and long-term data preservation. We are working collaboratively with ship operators and data managers to develop a prototype "data discovery system" for NSF-supported research vessels. Our goal is to establish infrastructure for a central shoreside repository, and to develop and test procedures for the routine delivery of standard data products and documentation to the repository. Related efforts are underway to identify tools and criteria for quality control of standard data products, and to develop standard interfaces and procedures for maintaining an underway event log. Development of a shoreside repository infrastructure will include: 1. Deployment and testing of a central catalog that holds cruise summaries and vessel profiles. A cruise summary will capture the essential details of a research expedition (operating institution, ports/dates, personnel, data inventory, etc.), as well as related documentation such as event logs and technical reports. A vessel profile will capture the essential details of a ship's installed instruments (manufacturer, model, serial number, reference location, etc.), with version control as the profile changes through time. The catalog's relational database schema will be based on the UNOLS Data Best Practices Committee's recommendations, and published as a formal XML specification. 2. Deployment and testing of a central repository that holds

  4. Preliminary analyses of scenarios for potential human interference for repositories in three salt formations

    Energy Technology Data Exchange (ETDEWEB)

    1985-10-01

    Preliminary analyses of scenarios for human interference with the performance of a radioactive waste repository in a deep salt formation are presented. The following scenarios are analyzed: (1) the U-Tube Connection Scenario involving multiple connections between the repository and the overlying aquifer system; (2) the Single Borehole Intrusion Scenario involving penetration of the repository by an exploratory borehole that simultaneously connects the repository with overlying and underlying aquifers; and (3) the Pressure Release Scenario involving inflow of water to saturate any void space in the repository prior to creep closure with subsequent release under near lithostatic pressures following creep closure. The methodology to evaluate repository performance in these scenarios is described and this methodology is applied to reference systems in three candidate formations: bedded salt in the Palo Duro Basin, Texas; bedded salt in the Paradox Basin, Utah; and the Richton Salt Dome, Mississippi, of the Gulf Coast Salt Dome Basin.

  5. Repository-Based Software Engineering Program: Working Program Management Plan

    Science.gov (United States)

    1993-01-01

    Repository-Based Software Engineering Program (RBSE) is a National Aeronautics and Space Administration (NASA) sponsored program dedicated to introducing and supporting common, effective approaches to software engineering practices. The process of conceiving, designing, building, and maintaining software systems by using existing software assets that are stored in a specialized operational reuse library or repository, accessible to system designers, is the foundation of the program. In addition to operating a software repository, RBSE promotes (1) software engineering technology transfer, (2) academic and instructional support of reuse programs, (3) the use of common software engineering standards and practices, (4) software reuse technology research, and (5) interoperability between reuse libraries. This Program Management Plan (PMP) is intended to communicate program goals and objectives, describe major work areas, and define a management report and control process. This process will assist the Program Manager, University of Houston at Clear Lake (UHCL) in tracking work progress and describing major program activities to NASA management. The goal of this PMP is to make managing the RBSE program a relatively easy process that improves the work of all team members. The PMP describes work areas addressed and work efforts being accomplished by the program; however, it is not intended as a complete description of the program. Its focus is on providing management tools and management processes for monitoring, evaluating, and administering the program; and it includes schedules for charting milestones and deliveries of program products. The PMP was developed by soliciting and obtaining guidance from appropriate program participants, analyzing program management guidance, and reviewing related program management documents.

  6. Central Satellite Data Repository Supporting Research and Development

    Science.gov (United States)

    Han, W.; Brust, J.

    2015-12-01

    Near real-time satellite data is critical to many research and development activities of atmosphere, land, and ocean processes. Acquiring and managing huge volumes of satellite data without (or with less) latency in an organization is always a challenge in the big data age. An organization level data repository is a practical solution to meeting this challenge. The STAR (Center for Satellite Applications and Research of NOAA) Central Data Repository (SCDR) is a scalable, stable, and reliable repository to acquire, manipulate, and disseminate various types of satellite data in an effective and efficient manner. SCDR collects more than 200 data products, which are commonly used by multiple groups in STAR, from NOAA, GOES, Metop, Suomi NPP, Sentinel, Himawari, and other satellites. The processes of acquisition, recording, retrieval, organization, and dissemination are performed in parallel. Multiple data access interfaces, like FTP, FTPS, HTTP, HTTPS, and RESTful, are supported in the SCDR to obtain satellite data from their providers through high speed internet. The original satellite data in various raster formats can be parsed in the respective adapter to retrieve data information. The data information is ingested to the corresponding partitioned tables in the central database. All files are distributed equally on the Network File System (NFS) disks to balance the disk load. SCDR provides consistent interfaces (including Perl utility, portal, and RESTful Web service) to locate files of interest easily and quickly and access them directly by over 200 compute servers via NFS. SCDR greatly improves collection and integration of near real-time satellite data, addresses satellite data requirements of scientists and researchers, and facilitates their primary research and development activities.

  7. Mining knowledge from text repositories using information extraction: A review

    Indian Academy of Sciences (India)

    Sandeep R Sirsat; Dr Vinay Chavan; Dr Shrinivas P Deshpande

    2014-02-01

    There are two approaches to mining text form online repositories. First, when the knowledge to be discovered is expressed directly in the documents to be mined, Information Extraction (IE) alone can serve as an effective tool for such text mining. Second, when the documents contain concrete data in unstructured form rather than abstract knowledge, Information Extraction (IE) can be used to first transform the unstructured data in the document corpus into a structured database, and then use some state-of-the-art data mining algorithms/tools to identify abstract patterns in this extracted data. This paper presents the review of several methods related to these two approaches.

  8. Copyright Solutions for Institutional Repositories: A Collaboration With Subject Librarians

    Directory of Open Access Journals (Sweden)

    Heather Leary

    2012-01-01

    Full Text Available This work investigates using subject librarians to conduct copyright clearance in an institutional repository (IR. At Utah State University, the library assures copyright clearance for faculty scholarship, thereby garnering input of faculty scholarship into the IR. Currently, subject librarians are not widely participating in routine IR work; however, the involvement of subject librarians with the IR offers benefits to the subject librarians and the institution as a whole. This article provides a model for institutions needing new solutions for copyright clearance using subject librarians and discusses the rationale, benefits and challenges of adopting this model.

  9. Repository criticality control for {sup 233}U using depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Forsberg, C.W.; Elam, K.R.; Hopper, C.M.

    1999-07-01

    The US is evaluating methods for the disposition of excess weapons-usable {sup 233}U, including disposal in a repository. Isotopic dilution studies were undertaken to determine how much depleted uranium (DU) would need to be added to the {sup 233}U to minimize the potential for nuclear criticality in a repository. Numerical evaluations were conducted to determine the nuclear equivalence of different {sup 235}U enrichments to {sup 233}U isotopically diluted with DU containing 0.2 wt% {sup 235}U. A homogeneous system of silicon dioxide, water, {sup 233}U, and DU, in which the ratio of each component was varied, was used to determine the conditions of maximum nuclear reactivity. In terms of preventing nuclear criticality in a repository, there are three important limits from these calculations. 1. Criticality safe in any nonnuclear system: The required isotopic dilution to ensure criticality under all conditions, except in the presence of man-made nuclear materials (beryllium, etc.), is {approximately}1.0% {sup 235}U in {sup 238}U. The equivalent {sup 233}U enrichment level is 0.53 wt% {sup 233}U in DU. 2. Critically safe in natural systems: The lowest {sup 235}U enrichment found in a natural reactor at shutdown was {approximately}1.3%. French studies, based on the characteristics of natural uranium ore bodies, indicate that a minimum enrichment of {approximately}1.28% {sup 235}U is required for criticality. These data suggest that nuclear criticality from migrating uranium is not realistic unless the {sup 235}U enrichments exceed {approximately}1.3%, which is a result that is equivalent to 0.72% {sup 233}U in DU. 3. Criticality safety equivalent to light water reactor (LWR) spent nuclear fuel (SNF): The {sup 233}U can be diluted with DU so that the uranium criticality characteristics match SNF uranium. Whatever repository criticality controls are used for SNF can then be used for {sup 233}U. The average LWR SNF assay (after decay of plutonium isotopes to uranium

  10. PGP repository: a plant phenomics and genomics data publication infrastructure.

    Science.gov (United States)

    Arend, Daniel; Junker, Astrid; Scholz, Uwe; Schüler, Danuta; Wylie, Juliane; Lange, Matthias

    2016-01-01

    Plant genomics and phenomics represents the most promising tools for accelerating yield gains and overcoming emerging crop productivity bottlenecks. However, accessing this wealth of plant diversity requires the characterization of this material using state-of-the-art genomic, phenomic and molecular technologies and the release of subsequent research data via a long-term stable, open-access portal. Although several international consortia and public resource centres offer services for plant research data management, valuable digital assets remains unpublished and thus inaccessible to the scientific community. Recently, the Leibniz Institute of Plant Genetics and Crop Plant Research and the German Plant Phenotyping Network have jointly initiated the Plant Genomics and Phenomics Research Data Repository (PGP) as infrastructure to comprehensively publish plant research data. This covers in particular cross-domain datasets that are not being published in central repositories because of its volume or unsupported data scope, like image collections from plant phenotyping and microscopy, unfinished genomes, genotyping data, visualizations of morphological plant models, data from mass spectrometry as well as software and documents.The repository is hosted at Leibniz Institute of Plant Genetics and Crop Plant Research using e!DAL as software infrastructure and a Hierarchical Storage Management System as data archival backend. A novel developed data submission tool was made available for the consortium that features a high level of automation to lower the barriers of data publication. After an internal review process, data are published as citable digital object identifiers and a core set of technical metadata is registered at DataCite. The used e!DAL-embedded Web frontend generates for each dataset a landing page and supports an interactive exploration. PGP is registered as research data repository at BioSharing.org, re3data.org and OpenAIRE as valid EU Horizon 2020 open

  11. A Semantically Enabled Metadata Repository for Solar Irradiance Data Products

    Science.gov (United States)

    Wilson, A.; Cox, M.; Lindholm, D. M.; Nadiadi, I.; Traver, T.

    2014-12-01

    The Laboratory for Atmospheric and Space Physics, LASP, has been conducting research in Atmospheric and Space science for over 60 years, and providing the associated data products to the public. LASP has a long history, in particular, of making space-based measurements of the solar irradiance, which serves as crucial input to several areas of scientific research, including solar-terrestrial interactions, atmospheric, and climate. LISIRD, the LASP Interactive Solar Irradiance Data Center, serves these datasets to the public, including solar spectral irradiance (SSI) and total solar irradiance (TSI) data. The LASP extended metadata repository, LEMR, is a database of information about the datasets served by LASP, such as parameters, uncertainties, temporal and spectral ranges, current version, alerts, etc. It serves as the definitive, single source of truth for that information. The database is populated with information garnered via web forms and automated processes. Dataset owners keep the information current and verified for datasets under their purview. This information can be pulled dynamically for many purposes. Web sites such as LISIRD can include this information in web page content as it is rendered, ensuring users get current, accurate information. It can also be pulled to create metadata records in various metadata formats, such as SPASE (for heliophysics) and ISO 19115. Once these records are be made available to the appropriate registries, our data will be discoverable by users coming in via those organizations. The database is implemented as a RDF triplestore, a collection of instances of subject-object-predicate data entities identifiable with a URI. This capability coupled with SPARQL over HTTP read access enables semantic queries over the repository contents. To create the repository we leveraged VIVO, an open source semantic web application, to manage and create new ontologies and populate repository content. A variety of ontologies were used in

  12. Implementation of an OAIS Repository Using Free, Open Source Software

    Science.gov (United States)

    Flathers, E.; Gessler, P. E.; Seamon, E.

    2015-12-01

    The Northwest Knowledge Network (NKN) is a regional data repository located at the University of Idaho that focuses on the collection, curation, and distribution of research data. To support our home institution and others in the region, we offer services to researchers at all stages of the data lifecycle—from grant application and data management planning to data distribution and archive. In this role, we recognize the need to work closely with other data management efforts at partner institutions and agencies, as well as with larger aggregation efforts such as our state geospatial data clearinghouses, data.gov, DataONE, and others. In the past, one of our challenges with monolithic, prepackaged data management solutions is that customization can be difficult to implement and maintain, especially as new versions of the software are released that are incompatible with our local codebase. Our solution is to break the monolith up into its constituent parts, which offers us several advantages. First, any customizations that we make are likely to fall into areas that can be accessed through Application Program Interfaces (API) that are likely to remain stable over time, so our code stays compatible. Second, as components become obsolete or insufficient to meet new demands that arise, we can replace the individual components with minimal effect on the rest of the infrastructure, causing less disruption to operations. Other advantages include increased system reliability, staggered rollout of new features, enhanced compatibility with legacy systems, reduced dependence on a single software company as a point of failure, and the separation of development into manageable tasks. In this presentation, we describe our application of the Service Oriented Architecture (SOA) design paradigm to assemble a data repository that conforms to the Open Archival Information System (OAIS) Reference Model primarily using a collection of free and open-source software. We detail the design

  13. Using XSLT and Google Scripts to Streamline Populating an Institutional Repository

    Directory of Open Access Journals (Sweden)

    Stephen X. Flynn

    2013-01-01

    Full Text Available The College of Wooster has created a process that allows library staff to quickly populate institutional repositories. An XSLT script is used to transform RefWorks citations into Dublin Core XML and batch load those records into the institutional repository. A second script in a Google Docs spreadsheet then looks up publisher permissions in Sherpa/RoMEO. The resulting workflow has dramatically reduced the amount of time necessary to populate an institutional repository with faculty scholarly articles.

  14. A Chemoprevention Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    Science.gov (United States)

    2007-02-01

    each subject’s baseline history of smoking, diet and tea intake, plasma catechins , and levels biomarkers of oxidative stress at baseline. All...Effects of High Tea Consumption on Smoking-Related Oxidative Stress PRINCIPAL INVESTIGATOR: Iman A. Hakim, MD, Ph., MPH...3. DATES COVERED (From - To) 13 Jul 06 – 12 Jan 07 4. TITLE AND SUBTITLE A Chemoprevention Trial to Study the Effects of High Tea Consumption on 5a

  15. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    OpenAIRE

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the proce...

  16. Hydrothermal modeling for the efficient design of thermal loading in a nuclear waste repository

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Won-Jin, E-mail: wjcho@kaeri.re.kr; Kim, Jin-Seop; Choi, Heui-Joo

    2014-09-15

    Highlights: • Three-dimensional hydrothermal modeling for HLW repository is performed. • The model reduces the peak temperature in the repository by about 10 °C. • Decreasing the tunnel distance is more efficient to improve the disposal density. • The EDZ surrounding the deposition hole increases the peak temperature. • The peak temperature for the double-layer repository remains below the limit. - Abstract: The thermal analysis of a geological repository for nuclear waste using the three-dimensional hydrothermal model is performed. The hydrothermal model reduces the maximum peak temperature in the repository by about 10 °C compared to the heat conduction model with constant thermal conductivities. Decreasing the tunnel distance is more efficient than decreasing the deposition hole spacing to improve the disposal density for a given thermal load. The annular excavation damaged zone surrounding the deposition hole has a considerable effect on the peak temperature. The possibility of double-layer repository is analyzed from the viewpoint of the thermal constraints of the repository. The maximum peak temperature for the double-layer repository is slightly higher than that for the single-layer repository, but remains below the temperature limit.

  17. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  18. Azathioprine, mucosal healing in ulcerative colitis, and the chemoprevention of colitic cancer: a clinical-practice-based forecast.

    Science.gov (United States)

    Actis, Giovanni C; Pellicano, Rinaldo; David, Ezio; Sapino, Anna

    2010-03-01

    The development of colorectal cancer in ulcerative colitis is a function of disease duration, with the risk approaching 14% at 25 years. Colitic cancer has become an issue in the last decades, as the availability of effective immune suppressors has reduced resort to curative colectomies. Scrutiny of the available drug options for ulcerative colitis has generated solid evidence of a chemopreventive role of mesalamines. Recent studies on the thiopurines azathioprine and mercaptopurine have unraveled the ability of these drugs to reduce inflammation and influence adaptive immunity by enhancing apoptosis. This evidence, speaking in favor of a chemopreventive role of thiopurines, has not been supported until recently by clinical studies. By contrast, endoscopic and clinical data in our hands have continued to suggest such a role: of a cohort of ulcerative colitis patients treated with azathioprine for 17 years, those on active treatment had no mucosal inflammation on endoscopy and overall none in this cohort developed cancer. This retrospective data have now been validated by cutting-edge information from a prospective nationwide study from an independent group which found a significant chemopreventive effect of azathioprine in those with extended long-standing colitis. Combination of our single-center experience with the data from this large study strongly indicates that the immune modulatory properties of thiopurines can translate into clinically meaningful anti-cancer activity in colitis. These results are likely to influence the medical choices of inflammatory bowel disease caregivers in the decades to come.

  19. The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma:a systematic review

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai; Stephanie H. Y. Lau

    2009-01-01

    BACKGROUND: Following curative treatment for hepato-cellular carcinoma (HCC), 50%-90% of postoperative death is due to recurrent disease. Intra-hepatic recurrence is frequently the only site of recurrence. Thus, any neoadjuvant or adjuvant therapy, which can decrease or delay the incidence of intra-hepatic recurrence, or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant, will improve the results of liver resection. This article systematically reviewed the current evidence of neoadjuvant, adjuvant, and chemoprevention in partial hepatectomy of HCC. DATA SOURCES: Studies were identiifed by searching MEDLINE and PubMed databases for articles from January 1990 to November 2008 using the keywords"hepatocellular carcinoma", "hepatectomy", "adjuvant therapy", "neoadjuvant therapy", and "regional therapy". Additional papers and book chapters were identiifed by a manual search of the references from the key articles. RESULTS: Neoadjuvant transarterial chemoembolization or adjuvant regional transarterial chemotherapy± embolization+systemic chemotherapy did not add beneift. Both adjuvant transarterial radioembolization with 131I-lipiodol and adjuvant systemic interferon showed promising results. However, there were only a limited number of such studies.CONCLUSIONS: Further randomized controlled studies need to be carried out. Currently, there is no consensus on a standard neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for HCC.

  20. Chemopreventive efficacy of menthol on carcinogen-induced cutaneous carcinoma through inhibition of inflammation and oxidative stress in mice.

    Science.gov (United States)

    Liu, Zhaoguo; Shen, Cunsi; Tao, Yu; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Shan, Yunlong; Zhu, Pingting; Sun, Lihua; Chen, Chen; Wang, Aiyun; Zheng, Shizhong; Lu, Yin

    2015-08-01

    Inflammation and oxidative stress have been implicated in various pathological processes including skin tumorigenesis. Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality, the treatment progress of which remains slow though. Therefore, chemoprevention and other strategies are being considered. Menthol has shown high anticancer activity against various human cancers, but its effect on skin cancer has never been evaluated. We herein investigated the chemopreventive potential of menthol against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, oxidative stress and skin carcinogenesis in female ICR mice. Pretreatment with menthol at various doses significantly suppressed tumor formation and growth, and markedly reduced tumor incidence and volume. Moreover, menthol inhibited TPA-induced skin hyperplasia and inflammation, and significantly suppressed the expression of cyclooxygenase-2 (COX-2). Furthermore, pretreatment with menthol inhibited the formation of reactive oxygen species and affected the activities of a battery of antioxidant enzymes in the skin. The expressions of NF-κB, Erk and p38 were down-regulated by menthol administration. Thus, inflammation and oxidative stress collectively played a crucial role in the chemopreventive efficacy of menthol on the murine skin tumorigenesis.