Chemoprevention by WR-2721

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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.

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

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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.

Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

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Raju, Jayadev; Mehta, Rekha

2009-01-01

Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

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Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

2011-01-01

From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

Breast Cancer Profile among Patients with a History of Chemoprevention

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Freya R. Schnabel

2016-01-01

Full Text Available Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer and secondary (previous history of breast cancer groups and compared to patients who never took chemoprevention. Results. 135 (6% of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%, 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65% and were diagnosed with equal percentages (44% of IDC and DCIS. 117 (87% used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65% than the nonchemoprevention group (84%/72%. In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients.

Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

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McCormick, D L; Rao, K V

1999-01-01

The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

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Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

2017-05-03

Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

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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.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond

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Stockbrugger, Reinhold W.

2010-01-01

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone o...

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

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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 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 stopped-flow UV-vis kinetics at 298 K. The potential chemopreventive role of KDE is discussed.

Curcumin in chemoprevention of breast cancer

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Katarzyna Terlikowska

2014-01-01

Full Text Available Breast cancer is the most common malignant cancer among women, both in Poland and worldwide. Due to the constantly increasing number of breast cancer cases, it is vital to develop effective activities in primary and secondary prevention. One of the promising methods of best value, connecting both types of cancer prevention, appears to be chemoprevention. Chemoprevention uses natural or synthetic compounds to inhibit, delay or reverse the process of carcinogenesis. Among ingredients of natural origin, great attention is paid to curcumin – a broad-spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma longa L. Curcumin has a number of chemopreventive properties such as anti-inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The main problem associated with the use of curcumin as a chemopreventive agent in humans is its low absorption from the gastrointestinal tract, poor solubility in body fluids and low bioavailability. Current studies are underway to increase the bioavailability and effectiveness of curcumin in vivo. Good results in the prevention and the treatment of breast cancer could be ensured by curcumin nanoparticles coated with albumin, known as nanocurcumin. The studies using nanocurcumin, however, are still in the preclinical stage, which is why there is a need to conduct extensive long-term randomized clinical trials to determine its effectiveness.

Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application.

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Wang, Zhijun; Fan, Jeffery; Liu, Mandy; Yeung, Steven; Chang, Andy; Chow, Moses S S; Pon, Doreen; Huang, Ying

2013-12-01

Nutraceutical is a food, or part of a food, used for the prevention and/or treatment of diseases. A number of nutraceuticals serve as candidates for development of prostate cancer chemopreventive agents because of promising epidemiological, preclinical and pilot clinical findings. Their mechanisms of action may involve an ability to target multiple molecular pathways in carcinogenesis without eliciting toxic side effects. This review provides an overview of several nutraceuticals, including green tea polyphenol, omega-3 fatty acids, vitamin D, lycopene, genistein, quercetin, resveratrol and sulforaphane, for the clinical relevance to chemoprevention of prostate cancer. Their mechanisms of action on regulating key processes of carcinogenesis are also discussed. For each of these agents, a brief summary of completed or currently ongoing clinical trials related to the chemopreventive efficacy on prostate cancer is given. Even though a few clinical trials have been conducted, review of these results indicate that further studies are required to confirm the clinical efficacy and safety, and to provide a guidance on how to use nutraceuticals for optimal effect. Future cancer prevention clinical trials for the nutraceuticals should recruit men with an increased risk of prostate cancer.

Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability.

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Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli

2011-12-14

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond.

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Stockbrugger, Reinhold W

2010-01-01

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further.

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

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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.

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

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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.

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

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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.

Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

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DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

The strategies to control prostate cancer by chemoprevention approaches

International Nuclear Information System (INIS)

Ting, Harold; Deep, Gagan; Agarwal, Chapla; Agarwal, Rajesh

2014-01-01

Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use

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

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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.

Phase 0 Clinical Chemoprevention Trial of the AKT Inhibitor SR13668

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Reid, Joel M.; Walden, Chad; Qin, Rui; Allen Ziegler, Katie L.; Haslam, John L.; Rajewski, Roger A.; Warndahl, Roger; Fitting, Cindy L.; Boring, Daniel; Szabo, Eva; Crowell, James; Perloff, Marjorie; Jong, Ling; Mandrekar, Sumithra J.; Ames, Matthew M.; Limburg, Paul J.

2011-01-01

Purpose SR13668, an orally active AKT pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Patients and Methods Healthy adult volunteers were randomly assigned to receive a single, 38 mg oral dose of SR13668 in one of five different formulations, with or without food. Based on existing animal data, SR13668 in a PEG400/Labrasol® oral solution was defined as the reference formulation. Blood samples were obtained pre- and post-agent administration for pharmacokinetic analyses. Area under the plasma concentration-time curve (AUC0-∞) was defined as the primary endpoint. Data were analyzed and compared using established statistical methods for phase 0 trials with a limited sample size. Results Participants (N=20) were rapidly accrued over a 5-month period. Complete pharmacokinetic data were available for 18 randomized participants. AUC0-∞ values were highest in the fed state (range = 122–439 ng/mL × hours) and were statistically significantly different across formulations (p = 0.007), with Solutol® HS15 providing the highest bioavailability. SR13668 time to peak plasma concentration (3 hours; range, 2 – 6 hours) and half-life were (11.2 ± 3.1 hours) were not formulation dependent. Conclusions Using a novel, highly efficient study design, we rapidly identified a lead formulation of SR13668 for further clinical testing. Our findings support application of the phase 0 trial paradigm to accelerate chemoprevention agent development. PMID:21372034

Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

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Milić Aleksandra

2013-01-01

Full Text Available Colorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors. The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids, reduced intake of minerals and vitamins as well as changes in pH of feces lead to initiation of the process of carcinogenesis in mucosa of the colon. Cancer chemoprevention is defined as the use of chemical agents in order to block, prevent or delay the reversal development or progress of cancer. It is believed that chemoprevention is a key component of cancer control, and numerous studies indicate potential role of NSAIDs in chemoprevention of colon cancer.

Comet Assay in Cancer Chemoprevention.

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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.

Moringa oleifera Lam: Targeting Chemoprevention.

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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.

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

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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.

Evidence supporting the conceptual framework of cancer chemoprevention in canines.

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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".

Cancer Chemoprevention by Carotenoids

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Takuji Tanaka

2012-03-01

Full Text Available Carotenoids are natural fat-soluble pigments that provide bright coloration to plants and animals. Dietary intake of carotenoids is inversely associated with the risk of a variety of cancers in different tissues. Preclinical studies have shown that some carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles for the compounds. Since chemoprevention is one of the most important strategies in the control of cancer development, molecular mechanism-based cancer chemoprevention using carotenoids seems to be an attractive approach. Various carotenoids, such as β-carotene, a-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti-carcinogenic activity in several tissues, although high doses of β-carotene failed to exhibit chemopreventive activity in clinical trials. In this review, cancer prevention using carotenoids are reviewed and the possible mechanisms of action are described.

The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma.

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Lee, Ui-Lyong; Choi, Sung-Weon

2011-01-01

Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

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

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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.

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

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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.

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

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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.

[Coffee in Cancer Chemoprevention].

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Neuwirthová, J; Gál, B; Smilek, P; Urbánková, P

Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

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Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

2006-12-15

The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

Cancer chemopreventive property of Bidens pilosa methanolic ...

African Journals Online (AJOL)

Cancer chemopreventive property of Bidens pilosa methanolic extract on two stage in vivo skin carcinogenesis model. ... In the forestomach, kidney and lung, glutathione S-transferase and DT-diaphorase levels were significantly reduced. Chemopreventive response was calculated by the mean number of papillomas ...

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

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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

Innovative agents in cancer prevention.

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Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

2005-01-01

There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

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

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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.

Chemopreventive effect of tadalafil in cisplatin-induced ...

African Journals Online (AJOL)

Summary: 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 ...

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

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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

Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

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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.

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

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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.

Ellagitannins in Cancer Chemoprevention and Therapy

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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.

Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells.

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Siddappa, Gangotri; Kulsum, Safeena; Ravindra, Doddathimmasandra Ramanjanappa; Kumar, Vinay V; Raju, Nalini; Raghavan, Nisheena; Sudheendra, Holalugunda Vittalamurthy; Sharma, Anupam; Sunny, Sumsum P; Jacob, Tina; Kuruvilla, Binu T; Benny, Merina; Antony, Benny; Seshadri, Mukund; Lakshminarayan, Padma; Hicks, Wesley; Suresh, Amritha; Kuriakose, Moni A

2017-11-01

Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4-nitro quinoline-1-oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40-100-fold) and protein levels (P ≤ 0.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4 mm 3 ; P = 0.04) and improved overall survival of the animals (P = 0.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO-induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (P oral squamous cell carcinoma through a CSC-associated mechanism. © 2017 Wiley Periodicals, Inc.

Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

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Bagde, Arvind; Mondal, Arindam; Singh, Mandip

2018-01-01

Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

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

2012-05-01

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

Plant flavonoids in cancer chemoprevention: role in genome stability.

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George, Vazhappilly Cijo; Dellaire, Graham; Rupasinghe, H P Vasantha

2017-07-01

Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer. Flavonoids are naturally occurring polyphenols that are ubiquitous in plant-based food such as fruits, vegetables and teas as well as in most medicinal plants. Over 10,000 flavonoids have been characterized over the last few decades. Flavonoids comprise of several subclasses including flavonols, flavan-3-ols, anthocyanins, flavanones, flavones, isoflavones and proanthocyanidins. This review describes the most efficacious plant flavonoids, including luteolin, epigallocatechin gallate, quercetin, apigenin and chrysin; their hormetic effects; and the molecular basis of how these flavonoids contribute to the chemoprevention with a focus on protection against DNA damage caused by various carcinogenic factors. The present knowledge on the role of flavonoids in chemoprevention can be used in developing effective dietary strategies and natural health products targeted for cancer chemoprevention. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

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Fangping Li

2018-03-01

Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

Chemopreventive properties of curcumin analogues ...

African Journals Online (AJOL)

Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)

International Nuclear Information System (INIS)

Arbab, Ali S; Shankar, Adarsh; Varma, Nadimpalli RS; Deeb, Dorrah; Gao, Xiaohua; Iskander, ASM; Janic, Branislava; Ali, Meser M; Gautam, Subhash C

2011-01-01

The current method to determine the efficacy of chemoprevention in TRAMP mouse model of carcinoma of prostate (CaP) is by extracting and weighing the prostate at different time points or by immunohistochemistry analysis. Non-invasive determination of volumes of prostate glands and seminal vesicles before, during and after treatment would be valuable in investigating the efficacy of newer chemopreventive agents in CaP. The purpose of this study was to determine whether in vivo magnetic resonance imaging (MRI) using a 3 tesla clinical MRI system can be used to follow the effect of chemoprevention in TRAMP model of mouse CaP. Mice were randomized into control and treated groups. The animals in treated group received 10 µmol/kg of CDDO, 5 days a week for 20 weeks. Animals underwent in vivo MRI of prostate gland and seminal vesicles by a clinical 3 Tesla MRI system just before (at 5 weeks), during and at the end of treatment, at 25 weeks. T1-weighted and fat saturation (FATSAT) multiecho fast spin echo T2- weighted images (T2WI) were acquired. Volume of the prostate glands and seminal vesicles was determined from MR images. T2 signal intensity changes in the seminal vesicles were determined by subtracting higher echo time (TE) from lower TE T2WI. Following treatments all animals were sacrificed, prostate and seminal vesicles collected, and the tissues prepared for histological staining. All data were expressed as mean ± 1 standard deviation. Two-way or multivariate analysis of variance followed by post-hoc test was applied to determine the significant differences. A p-value of <0.05 was considered significant. Histological analysis indicated tumor in 100% of control mice, whereas 10% of the treated mice showed tumor in prostate gland. Both MRI and measured prostate weights showed higher volume/weight in control mouse group. MRI showed significantly higher volume of seminal vesicles in control animals and T2 signal intensity changes in seminal vesicles of control mice

Antimutagenic constituents of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) with potential cancer chemopreventive activity.

Science.gov (United States)

Chen, Huang-Hui; Chiang, Wenchang; Chang, Jang-Yang; Chien, Ya-Lin; Lee, Ching-Kuo; Liu, Ko-Jiunn; Cheng, Yen-Ting; Chen, Ting-Fang; Kuo, Yueh-Hsiung; Kuo, Ching-Chuan

2011-06-22

Adlay has long been used in traditional Chinese medicine and as a nourishing food. The acetone extract of adlay hull had previously been demonstrated to possess potent antimutagenic activity. The aims of this study were to identify the antimutagenic constituents from adlay hull by using Ames antimutagenic activity-guide isolation procedures and to investigate their chemopreventive efficacies in cultured cells. The results demonstrated that six compounds showing great antimutagenic activity were identified by spectroscopic methods and by comparison with authentic samples to be p-hydroxybenzaldehyde, vanillin, syringaldehyde, trans-coniferylaldehyde, sinapaldehyde, and coixol. Two of them, trans-coniferylaldehyde and sinapaldehyde, exhibit relatively potent scavenging of DPPH radicals, inhibit TPA stimulated superoxide anion generation in neutrophil-like leukocytes, and induce Nrf2/ARE-driven luciferase activity in HSC-3 cells. Moreover, trans-coniferylaldehyde possesses cytoprotective efficacy against tert-butyl hydroperoxide-induced DNA double-strand breaks in cultured cells, and the chemopreventive potency induced by trans-coniferylaldehyde may be through the activation of kinase signals, including p38, ERK1/2, JNK, MEK1/2, and MSK1/2. In summary, we first identified six antimutagenic constituents from adlay hull. Among them, trans-coniferylaldehyde would be a highly promising agent for cancer chemoprevention and merits further investigation.

A Chemopreventive Nanodiamond Platform for Oral Cancer Treatment.

Science.gov (United States)

Yen, Albert; Zhang, Kangyi; Daneshgaran, Giulia; Kim, Ho-Joong; Ho, Dean

2016-02-01

Standard oral cancer therapy generally includes a combination of surgery with chemotherapy and/or radiotherapy. This treatment paradigm has not changed in some time. In this paper, we propose a chemopreventive nanodiamond platform for the delivery of celecoxib (Celebrex) to oral cancer lesions. This innovative platform allows for sustained drug release under physiological conditions, potentially enhancing chemopreventive efficacy of celecoxib without the physical and toxicological damage associated with conventional means of drug delivery.

In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

Science.gov (United States)

Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

2018-03-01

Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

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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.

Carcinogenicity of chromium and chemoprevention: a brief update

Directory of Open Access Journals (Sweden)

Wang Y

2017-08-01

Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

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

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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.

Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

Science.gov (United States)

Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

2005-03-01

Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

Science.gov (United States)

Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

2015-02-01

Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

Science.gov (United States)

Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

2015-01-01

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo.

Science.gov (United States)

Hagos, Ghenet K; Carroll, Robert E; Kouznetsova, Tatiana; Li, Qian; Toader, Violeta; Fernandez, Patricia A; Swanson, Steven M; Thatcher, Gregory R J

2007-08-01

Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.

Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

Science.gov (United States)

Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

1998-03-01

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

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.

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

International Nuclear Information System (INIS)

Heidor, Renato; Furtado, Kelly Silva; Ortega, Juliana Festa; Oliveira, Tiago Franco de; Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino; Purgatto, Eduardo; Moreno, Fernando Salvador

2014-01-01

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

Effect of Food Sources of Natural Chemo preventive Agents on ...

African Journals Online (AJOL)

Objective: The work attempted to evaluate the potential of natural products containing cancer chemopreventive agents in increasing the level of some endogenous antioxidant enzymes such as Glutathione STransferase (GST), Glutathione reductase (GR), catalase, superoxide dismutase(SOD-1,2) in brain and kidney ...

Chemical carcinogenesis and chemoprevention: Scientific priority ...

African Journals Online (AJOL)

Occupational cancers are now a serious concern in industrializing developing countries where exposure levels to hazardous chemicals considerably exceed regulatory limits established in industrialized countries. The association between increasing use of chemicals and associated disorders and chemoprevention or ...

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

The Format Converting/Transfer Agent and Repository System based on ebXML

Directory of Open Access Journals (Sweden)

KyeongRim Ahn

2004-12-01

Full Text Available As introducing XML in EC-environment, various document formats have been used due to XML characteristic. Also, other document format except XML have been used to exchange EC-related information. That is, as increasing trading partner, as increasing exchanged document format and business processing being complex. So, management difficulty and duplication problem happened as trading partners increasing. And, they want to change plural business workflow to general and uniform form as defining and arranging BP(Business Process. Therefore, in this paper, we define XML as future document standard agreement and discuss about service system architecture and Repository. Repository stores and manages document standard, information related to Business Processing, Messaging Profile, and so on. Repository structure is designed to cover various XML standards. Also, we design system to support ebXML communication protocol, MSH, as well as traditional communication protocol, such as X.25, X.400, etc. and implement to exchange information via FTP.

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.......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....

Arsenic and skin cancer – Case report with chemoprevention

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Uwe Wollina

2016-04-01

Full Text Available ABSTRACT Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids. Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar minute keratoses. To prevent a transformation into invasive cancer and to lower the burden of precancerous and in situ cancer lesions, he was treated orally with acitretin 20 mg/day. During 9 months of chemopreventive retinoid therapy a partial response of pre-existent skin lesions was noted. Treatment was well tolerated. During follow-up of 5 years no invasive malignancy developed. Conclusions: Intense exposure to arsenics during a relatively short period of 3 years bears a life-long health hazard with the delayed development of multiple in situ carcinomas and precancerous lesions. Chemoprevention with retinoids can induce a partial response.

Colorectal cancer chemoprevention: the potential of a selective approach.

Science.gov (United States)

Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

2010-10-01

Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

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

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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.

Pathobiology and Chemoprevention of Bladder Cancer

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Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

2011-01-01

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

Combination Chemoprevention with Grape Antioxidants

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Singh, Chandra K.; Siddiqui, Imtiaz A.; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

2016-01-01

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resver...

Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

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Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

2016-09-01

Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endotoxin and cancer chemo-prevention.

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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. Copyright © 2013 Elsevier Ltd. All rights reserved.

500 year concrete for a radioactive waste repository

International Nuclear Information System (INIS)

Philipose, K.E.

1988-03-01

The IRUS (Intrusion resistant underground structure) repository planned at Chalk River for the belowground disposal of low level radioactive waste relies on the durability of concrete for the required 500 year service life. A research program for the IRUS repository to design a durable concrete and also to predict its longevity under the repository environment is in progress. The methodology involves the identification of major degradation agents, and the assessment of the rate of diffusion of corrosive ions and/or the rate of advancement of the reaction front into the concrete. Accelerated test methods are being used on laboratory specimens in conjunction with extrapolation procedures to predict long-term durability from short-term data. The inherent limitations are also examined

Evaluating the potential cancer chemopreventive efficacy of two different solvent extracts of Seriphidium herba-alba in vitro

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Mahmoud Mohamed Mokhtar

2017-06-01

Full Text Available Cancer is the second leading cause of death world-wide. One of the most important medical practices of the 21st century is the chemoprevention of cancer. For a long history, it has been accepted that plants could prevent and exert suitable anti-carcinogenic effects for multiple types of cancers. Seriphidium herba-alba family Asteraceae has been used in the folk medicine by many cultures for treatment of various ailments since ancient times. In the current research we were aimed to evaluate the cancer chemopreventive activity of two crude extracts of S. herba-alba, methylene chloride extract and methanol extract on two cell lines: Human breast cancer cells (MCF-7 and human hepatocellular carcinoma cells (Hep-G2. Assessment of cytotoxicity using methyl thiazole tetrazolium (MTT assay indicated that both extracts exhibit poor cytotoxicity with half maximal inhibitory concentration (IC50 >20 µg/mL. Assessment of glutathione-S-transferases (GSTs activity (spectrophotometrically showed statistically significant enhancement of enzyme activity after treatment with three different doses of methylene chloride extract and glutathione (GSH concentrations were decreased. Analysis of cell mode of death by Ethidium bromide/Acridine orange (EB/AO staining revealed that the dominant mode of death in MCF-7 cells was apoptosis. Assessment of vascular endothelial growth factor (VEGF and platelets derived growth factor (PDGFBB using ELISA showed that VEGF and PDGFBB levels were statistically significant decreased. In Conclusion: both extracts may be cancer chemopreventive agents since they had tumor anti-initiating, and anti-promoting activity.

Resveratrol: Chemoprevention with red wine

OpenAIRE

Arısan, Elif Damla; Palavan-Ünsal, Narçin

2007-01-01

According to epidemiological studies, western diet has disadvantages because of cancer prevalence more than Mediterranean or Asia people who consume more vegetables and fruits. Resveratrol (trans-3,4,5-trihydroxystilbene) which is highly found in grapes, berries has received attention for its potential chemopreventive and antitumor effects in experimental systems. Because of high resveratrol content, researchers noted that red wine has multidimensional benefits for ...

Cancer Chemoprevention by Resveratrol: The p53 Tumor Suppressor Protein as a Promising Molecular Target

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Danielly C. Ferraz da Costa

2017-06-01

Full Text Available Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol is a diet-derived cancer chemopreventive agent with high therapeutic potential, as demonstrated by different authors. The aim of this review is to collect and present recent evidence from the literature regarding resveratrol and its effects on cancer prevention, molecular signaling (especially regarding the involvement of p53 protein, and therapeutic perspectives with an emphasis on clinical trial results to date.

Cancer chemoprevention through dietary flavonoids: what's limiting?

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Amawi, Haneen; Ashby, Charles R; Tiwari, Amit K

2017-06-19

Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug-drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

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Chen, Lianguo [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Au, Doris W.T. [State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Hu, Chenyan [School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072 (China); Zhang, Weipeng [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Cai, Lin [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Giesy, John P. [Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3 (Canada); Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Qian, Pei-Yuan, E-mail: boqianpy@ust.hk [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China)

2017-02-15

combination with chemical stability and potent endocrine disruption, the results of this study can inform decisions about the use of DIM either as chemopreventive or antifouling agent.

Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

International Nuclear Information System (INIS)

Chen, Lianguo; Au, Doris W.T.; Hu, Chenyan; Zhang, Weipeng; Zhou, Bingsheng; Cai, Lin; Giesy, John P.; Qian, Pei-Yuan

2017-01-01

combination with chemical stability and potent endocrine disruption, the results of this study can inform decisions about the use of DIM either as chemopreventive or antifouling agent.

Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

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Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

2015-04-01

Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

Quantification of 4'-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract.

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Genovese, S; Epifano, F; Carlucci, G; Marcotullio, M C; Curini, M; Locatelli, M

2010-10-10

Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy-compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been consider for years merely as biosynthetic intermediates of the most abundant C-prenylated derivatives. Many of the isolated oxyprenylated natural products were shown to exert in vitro and in vivo remarkable anti-cancer and anti-inflammatory effects. 4'-Geranyloxyferulic acid [3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic] has been discovered as a valuable chemopreventive agent of several types of cancer. After development of a high yield and "eco-friendly" synthetic scheme of this secondary metabolite, starting from cheap and non-toxic reagents and substrates, we developed a new HPLC-DAD method for its quantification in grapefruit skin extract. A preliminary study on C18 column showed the separation between GOFA and boropinic acid (having the same core but with an isopentenyloxy side chain), used as internal standard. The tested column were thermostated at 28+/-1 degrees C and the separation was achieved in gradient condition at a flow rate of 1 mL/min with a starting mobile phase of H(2)O:methanol (40:60, v/v, 1% formic acid). The limit of detection (LOD, S/N=3) was 0.5 microg/mL and the limit of quantification (LOQ, S/N=10) was 1 microg/mL. Matrix-matched standard curves showed linearity up to 75 microg/mL. In the analytical range the precision (RSD%) values were extract of grapefruit. In conclusion, this method showed LOQ values able to selective quantification of this analyte in grapefruit skin extract.

Organic complexing agents in low and medium level radioactive waste

International Nuclear Information System (INIS)

Allard, B.; Persson, G.

1985-11-01

Low and medium level radioactive wastes will contain various organic agents, such as ion exchange resins (mainly in the operational wastes), plastics and cellulose (mainly in the reprocessing wastes and in the decommissioning wastes) and bitumen (mainly in the reprocessing wastes). The degradation of these organics will lead to the formation of complexing agents that possibly could affect the release of radionuclides from an underground repository and the subsequent transport of these nuclides. The solution chemistry of the actinides may be totally dominated by the presence of such organic degradation products within the repository. However, hydrolysis and formation of carbonates (and possibly humates) will most likely dominate solubility and speciation outside the immediate vicinity of the repository. The minor quantities of strong complexing agents (in the reprocessing waste), notably aminopolycarboxylic acids (EDTA, DTPA) and possibly organic phosphates (DBP) could significantly affect speciation and sorption behaviour of primarily the trivalent actinides even outside the repository. (author)

Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice

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Kyung-Sook Chung

2018-02-01

Full Text Available Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG on azoxymethane/dextran sulfate sodium (AOM/DSS-induced colitis-associated cancer (CAC in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL-1β, IL-6, and tumor necrosis factor (TNF-α production and decreased inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα, leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2 family and inhibitors of apoptosis proteins (IAPs, in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.

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

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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.

State-of-the-art for evaluating the potential effects of erosion and deposition on a radioactive waste repository. Final report

International Nuclear Information System (INIS)

1980-01-01

The potential impact of future geologic processes on the integrity of a deep, high-level radioactive-waste repository is evaluated. The following study identifies the potential consequences of surface erosion and deposition on sub-surface repository containment characteristics and assesses the ability to measure and predict quantitatively the rates and corresponding extent of these processes in the long term. Numerous studies of the magnitudes and rates of surficial erosion and deposition that have been used to determine the minimum allowable depth for a geologic repository (300 m - NRC Code of Federal Regulations, Part 60.122, Draft 10) are cited in this report. Measurement and interpretation of potential rates and extent of surficial processes in these studies involved considerable uncertainty, and the implications of this uncertainty on presently proposed repository siting criteria are addressed herein. Important concepts that should be considered when developing siting criteria to protect against deleterious effects arising from future erosion or deposition are highlighted. Erosion agents that could affect deep repositories are distinguished in this report so that their individual and combined impacts may be examined. This approach is recommended when evaluating potential repository sites in diverse environments that are susceptible to different agents of erosion. In contrast, agents of sedimentation are not differentiated in this report because of their relatively minor impact on a deep repository

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

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Elad Ziv

Full Text Available 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.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.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.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.

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.

Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

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Veettil SK

2017-05-01

Full Text Available Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts, School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21 Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs against colorectal adenomas have been well documented in randomized controlled trials (RCTs; however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome. Using NMA, we

Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways

International Nuclear Information System (INIS)

Ahmad, Shiekh Tanveer; Arjumand, Wani; Seth, Amlesh; Nafees, Sana; Rashid, Summya; Ali, Nemat; Sultana, Sarwat

2011-01-01

Graphical abstract: Diagrammatic presentation of the hypothesis of the article in a concise manner. It reveals the chemopreventive efficacy of GOH possibly through the modulation of multiple molecular targets. GOH inhibits ROS generation, NFκB and PCNA expression thereby abrogating inflammation and proliferation of tubular cells of kidney. Whereas, GOH induces effector caspase-3 expression both through mitochondrial signalling pathway and death receptor signalling pathway. Highlights: → Geraniol modulates renal carcinogenesis in Wistar rats. → It abrogates Fe-NTA induced oxidative stress, inflammation and hyperproliferation. → Promotes apoptosis via induction of both mitochondrial and death receptor pathway. → Thus, inhibits renal carcinogenesis by modulating multiple molecular targets. -- Abstract: In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200 mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein

Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

Science.gov (United States)

Chen, Lili; Jiang, Bowen; Zhong, Chunge; Guo, Jun; Zhang, Lihao; Mu, Teng; Zhang, Qiuhua; Bi, Xiuli

2018-03-08

Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation.

Science.gov (United States)

Yoshigae, Yasushi; Sridar, Chitra; Kent, Ute M; Hollenberg, Paul F

2013-04-01

Phenethylisothiocyanate (PEITC), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 (P450) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens. PEITC has been reported to be a mechanism-based inactivator of some P450s. We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC. PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione (GSH) and not fully recovered by dialysis. The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation. GSH-adducts of phenethyl isocyanate (PIC) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450-catalyzed desulfurization of PEITC. Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme. Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo-protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1. Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion. Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC.

Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

Directory of Open Access Journals (Sweden)

Aymeric Monteillier

2018-03-01

Full Text Available Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway.

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...

Phyto-oestrogens and breast cancer chemoprevention

International Nuclear Information System (INIS)

Limer, Jane L; Speirs, Valerie

2004-01-01

Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

Adlay (薏苡 yì yĭ; “soft-shelled job's tears”; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes

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Ching-Chuan Kuo, Ph.D.

2012-10-01

Full Text Available Adlay (薏苡 yì yĭ; “soft-shelled job’s tears”, the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a grass crop that has long been used in traditional Chinese medicine (TCM and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article.

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

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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.

Evaluation of Nuclide Release Scenarios for a Hypothetical LILW Repository

International Nuclear Information System (INIS)

Lee, Youn Myoung; Jeong, Jong Tae

2010-11-01

A program for the safety assessment and performance evaluation of a low- and intermediate-level radioactive waste (LILW) repository system has been developed. Utilizing GoldSim (GoldSim, 2006), the program evaluates nuclide release and transport into the geosphere and biosphere under various disruptive natural and manmade events and scenarios that can occur after a waste package failure. We envisaged and illustrated these events and scenarios as occurring after the closure of a hypothetical LILW repository, and they included the degradation of various manmade barriers, pumping well drilling, and natural disruptions such as the sudden formation of a preferential flow pathway in the far-field area of the repository. Possible enhancement of nuclide transport facilitated by colloids or chelating agents is also dealt with. We used the newly-developed GoldSim template program, which is capable of various nuclide release scenarios and is greatly suited for simulating a potential repository given the geological circumstances in Korea, to create the detailed source term and near-field release scheme, various nuclide transport modes in the far-field geosphere area, and the biosphere transfer. Even though all parameter values applied to the hypothetical repository were assumed, the illustrative results, particularly the probabilistic calculations and sensitivity studies, may be informative under various scenarios

Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

Science.gov (United States)

Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

2011-01-01

Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

Cancer Chemopreventive Ability of Conjugated Linolenic Acids

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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.

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

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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.

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.

Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka.

Science.gov (United States)

Cibin, T R; Devi, D Gayathri; Abraham, Annie

2010-05-01

Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. Copyright (c) 2009 John Wiley & Sons, Ltd.

Learning Object Repositories

Science.gov (United States)

Lehman, Rosemary

2007-01-01

This chapter looks at the development and nature of learning objects, meta-tagging standards and taxonomies, learning object repositories, learning object repository characteristics, and types of learning object repositories, with type examples. (Contains 1 table.)

Study on the interaction of chemopreventive compounds and food born carcinogens with cytochrome P450 enzymes

OpenAIRE

Brabencová, Eliška

2013-01-01

The use of food supplements containing natural chemopreventive compounds increased in recent years. Some of the most popular chemopreventive compounds are flavonoids. Due to their natural origin, flavonoids are generally accepted as safe compounds. They exert antioxidant, anti-cancer and anti-inflammatory properties. However, flavonoids should be considered as foreign compounds (xenobiotics). Flavonoids interact with many enzymes, among the most important belong cytochromes P450 (CYPs), key e...

Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review.

Science.gov (United States)

Rafieian-Kopaei, Mahmoud; Movahedi, Mino

2017-02-01

Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified around 108 references. In this study, 68 studies were accepted for further screening, and met all our inclusion criteria [in English, full text, chemopreventive and chemotherapeutic effects of Camellia sinensis and dated mainly from the year 1999 to 2016. The search terms were Camellia sinensis, chemopreventive, chemotherapeutic properties, pharmacological effects. The result of this study suggested that the catechin available in Camellia sinensis has properties which can prevent and treat breast cancer. It has also been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. It was found that increased Camellia sinensis consumption may lower the risk of breast cancer. Camellia sinensis intake was shown to reduce the risk of breast cancer incidence. In addition, potential breast cancer chemopreventive effect of Camellia sinensis both in vivo and in vitro was highly confirmed. However, the evidence of low effect and no effect was observed. More clinical trial studies are needed to prove its anti-breast cancer activity decisively. Camellia sinensis is broadly utilized as a part of customary medication since antiquated time because of its cost adequacy, and fewer reaction properties. The studies demonstrated anti-breast cancer activity of Camellia sinensis and its component by adjusting cell signaling pathways such as angiogenesis, apoptosis, and transcription factor. Furthermore

Repository Rodeo Redux

CERN Document Server

Anez, Melissa; Donohue, Tim; Fyson, Will; Simko, Tibor; Wilcox, David

2017-01-01

You’ve got more repository questions and we’ve got more answers! Last year’s Repository Rodeo panel was a huge success, so we’re taking the show on the road to Brisbane for OR2017. Join representatives from the DSpace, Eprints, Fedora, Hydra, and Islandora communities as we (briefly) explain what each of our repositories actually does. We'll also talk about the directions of our respective technical and community developments, and related to the conference theme of Open: Innovation Knowledge Repositories, offer brief observations about the latest, most promising and/or most surprising innovations in our space. This panel will be a great opportunity for newcomers to Open Repositories to get a crash course on the major repository options and meet representatives from each of their communities. After a brief presentation from each representative, we'll open the session up for questions from the audience.

Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo.

Science.gov (United States)

Al-Henhena, Nawal; Khalifa, Shaden A M; Ying, Rozaida Poh Yuen; Ismail, Salmah; Hamadi, Riad; Shawter, Abdrabu N; Idris, Azila Mohd; Azizan, Ainnul; Al-Wajeeh, Nahla Saeed; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

2015-11-25

With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation. Five groups of rats were injected subcutaneously with AOM, 15 mg/kg body weight, each once weekly for 2 weeks. The cancer group was continued on 10 % Tween-20 feeding for 8 weeks. The standard drug group was continued on 35 mg/kg 5-fluorouracil intraperitoneal injection twice a week for 8 weeks, and the experimental groups were continued on 250 and 500 mg/kg S. crispus extract oral feeding for 8 weeks, respectively. The normal group was injected subcutaneously with normal saline once a week for 2 weeks, followed by oral administration of 10 % Tween-20 for 8 weeks. All the rats were sacrificed after 10 weeks. The colons were evaluated grossly and histopathologically for aberrant crypt foci (ACF). Gene expression was performed for Bax, Bcl2, Defa24, Slc24a3, and APC genes by real-time PCR. S. crispus and its fractions were evaluated for their chemopreventive effects against human colorectal adenocarcinoma cell line HT29 and cytotoxicity for normal human colon epithelial cell line CCD 841, and the active fraction was assessed for its components. We observed significant decrease in total colonic ACF formation, malonaldehyde (MDA) and lactate dehydrogenase (LDH), increase in superoxide dismutase (SOD), up-regulation of APC, Bax and Slc24a3, and down-regulation of Defa24 and Bcl-2 in rats treated with Strobilanthes

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. Copyright © 2015 John Wiley & Sons, Ltd.

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

Directory of Open Access Journals (Sweden)

Horng-Jyh Tsai

2015-04-01

Full Text Available 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.

EEI/UWASTE oversight of the DOE Repository Program by the Repository Information Exchange Team

International Nuclear Information System (INIS)

Henkel, C.J.; Supko, E.M.; Schwartz, M.H.

1993-01-01

The Utility Nuclear Waste and Transportation Program of the Edison Electric Institute (EEI/UWASTE) has conducted reviews of the US DOE's repository program through its Repository Information Exchange Team (RIET or Team). Eight such reviews have been conducted since 1985 covering topics that include repository program management and control; repository schedule; repository budget; quality assurance; site characterization; repository licensing; environmental issues; and institutional and public information activities. The utility industry has used these repository program reviews as a forum for providing DOE's Office of Civilian Radioactive Waste Management (OCRWM) with comments on the direction of the repository program, advice for future actions regarding quality assurance activities and repository licensing, and suggestions for management and control of the Repository Program. The most significant recommendations made by the utility industry through the RIET are discussed along with any subsequent action by OCRWM in response to or subsequent to utility industry recommendations. The process used by the RIET to develop its recommendations to OCRWM regarding the repository program is also discussed

Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats

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Zhenyu Wang

2017-05-01

Full Text Available Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA-induced mammary cancer in female Sprague Dawlely (SD rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p. were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

Update on the chemopreventive effects of ginger and its phytochemicals.

Science.gov (United States)

Baliga, Manjeshwar Shrinath; Haniadka, Raghavendra; Pereira, Manisha Maria; D'Souza, Jason Jerome; Pallaty, Princy Louis; Bhat, Harshith P; Popuri, Sandhya

2011-07-01

The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is one of the most widely used spice and condiment. It is also an integral part of many traditional medicines and has been extensively used in Chinese, Ayurvedic, Tibb-Unani, Srilankan, Arabic, and African traditional medicines, since antiquity, for many unrelated human ailments including common colds, fever, sore throats, vomiting, motion sickness, gastrointestinal complications, indigestion, constipation, arthritis, rheumatism, sprains, muscular aches, pains, cramps, hypertension, dementia, fever, infectious diseases, and helminthiasis. The putative active compounds are nonvolatile pungent principles, namely gingerols, shogaols, paradols, and zingerone. These compounds are some of the extensively studied phytochemicals and account for the antioxidant, anti-inflammatory, antiemetic, and gastroprotective activities. A number of preclinical investigations with a wide variety of assay systems and carcinogens have shown that ginger and its compounds possess chemopreventive and antineoplastic effects. A number of mechanisms have been observed to be involved in the chemopreventive effects of ginger. The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression. This review provides concise information from preclinical studies with both cell culture models and relevant animal studies by focusing on the mechanisms responsible for the chemopreventive action. The conclusion describes directions for future research to establish its activity and utility as a human cancer preventive and therapeutic drug. The above-mentioned mechanisms of ginger seem to be promising for cancer prevention; however, further clinical studies are warranted to assess the efficacy and safety of ginger.

Grapefruit and its biomedical, antigenotoxic and chemopreventive properties.

Science.gov (United States)

Cristóbal-Luna, José Melesio; Álvarez-González, Isela; Madrigal-Bujaidar, Eduardo; Chamorro-Cevallos, Germán

2018-02-01

Grapefruit (Citrus paradisi Mcfad) is a perenifolium tree 5-6 m high with a fruit of about 15 cm in diameter, protected by the peel we can find about 11-14 segments (carpels), each of which is surrounded by a membrane and each containing the juice sacs, as well as the seeds. The fruit is made up of numerous compounds, and is known to have nutritive value because of the presence of various vitamins and minerals, among other chemicals. The fruit is also used in the field of gastronomy. Information has been accumulated regarding the participation of the fruit structures in a variety of biomedical, antigenotoxic and chemopreventive effects, surely related with the presence of the numerous chemicals that have been determined to constitute the fruit. Such studies have been carried out in different in vitro and in vivo experimental models, and in a few human assays. The information published so far has shown interesting results, therefore, the aims of the present review are to initially examine the main characteristics of the fruit, followed by systematization of the acquired knowledge concerning the biomedical, antigenotoxic and chemopreventive effects produced by the three main structures of the fruit: peel, seed, and pulp. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Review of the Potential of Phytochemicals from Prunus africana (Hook f. Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

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Richard Komakech

2017-01-01

Full Text Available Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

Colon cancer chemoprevention with ginseng and other botanicals.

OpenAIRE

Wargovich, M J

2001-01-01

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

Science.gov (United States)

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

Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

Science.gov (United States)

Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

2009-09-01

The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials.

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.

Repository simulation model: Final report

International Nuclear Information System (INIS)

1988-03-01

This report documents the application of computer simulation for the design analysis of the nuclear waste repository's waste handling and packaging operations. The Salt Repository Simulation Model was used to evaluate design alternatives during the conceptual design phase of the Salt Repository Project. Code development and verification was performed by the Office of Nuclear Waste Isolation (ONWL). The focus of this report is to relate the experience gained during the development and application of the Salt Repository Simulation Model to future repository design phases. Design of the repository's waste handling and packaging systems will require sophisticated analysis tools to evaluate complex operational and logistical design alternatives. Selection of these design alternatives in the Advanced Conceptual Design (ACD) and License Application Design (LAD) phases must be supported by analysis to demonstrate that the repository design will cost effectively meet DOE's mandated emplacement schedule and that uncertainties in the performance of the repository's systems have been objectively evaluated. Computer simulation of repository operations will provide future repository designers with data and insights that no other analytical form of analysis can provide. 6 refs., 10 figs

Repositories; Repositorios

Energy Technology Data Exchange (ETDEWEB)

Freire, Carolina Braccini; Tello, Cledola Cassia Oliveira de [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)]. E-mails: cbf@cdtn.br; tellocc@cdtn.br

2007-11-15

The use of the nuclear energy is increasing in all areas. Then the radioactive waste management is in continuous development to comply the national and international established requirements. The final objective is to assure that it will not have any contamination of the public or the environmental, and that the exposition doses will be lower than the radiological protection limits. The multi barrier concept for the repository is internationally recognized. Among the repository types, the most used are: near surface, geological formations and of deposition in rock cavities. This article explains the concept and the types of repository and gives some examples of them. (author)

Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc−/+ mice

International Nuclear Information System (INIS)

Karim, Baktiar O; Rhee, Ki-Jong; Liu, Guosheng; Zheng, Dongfeng; Huso, David L

2013-01-01

Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies. We evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4 −/− mice to Apc −/+ mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc −/+ mice and HT-29 colon cancer cells in culture. Cdk4 −/− mice backcrossed to Apc −/+ mice reduced intestinal adenoma formation compared to Apc −/+ controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc −/+ mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin. Modification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas

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

Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

Science.gov (United States)

Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

2016-01-01

Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

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.

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

International Nuclear Information System (INIS)

Perocco, Paolo; Bronzetti, Giorgio; Canistro, Donatella; Valgimigli, Luca; Sapone, Andrea; Affatato, Alessandra; Pedulli, Gian Franco; Pozzetti, Laura; Broccoli, Massimiliano; Iori, Renato; Barillari, Jessica; Sblendorio, Valeriana; Legator, Marvin S.; Paolini, Moreno; Abdel-Rahman, Sherif Z.

2006-01-01

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

Managing and Evaluating Digital Repositories

Science.gov (United States)

Zuccala, Alesia; Oppenheim, Charles; Dhiensa, Rajveen

2008-01-01

Introduction: We examine the role of the digital repository manager, discuss the future of repository management and evaluation and suggest that library and information science schools develop new repository management curricula. Method: Face-to-face interviews were carried out with managers of five different types of repositories and a Web-based…

Repository simulation tests

International Nuclear Information System (INIS)

Wicks, G.G.; Bibler, N.E.; Jantzen, C.M.; Plodinec, M.J.

1984-01-01

The repository simulation experiments described in this paper are designed to assess the performance of SRP waste glass under the most realistic repository conditions that can be obtained in the laboratory. These tests simulate the repository environment as closely as possible and introduce systematically the variability of the geology, groundwater chemistry, and waste package components during the leaching of the waste glass. The tests evaluate waste form performance under site-specific conditions, which differ for each of the geologic repositories under consideration. Data from these experiments will aid in the development of a realistic source term that can describe the release of radionuclides from SRP waste glass as a component of proposed waste packages. Hence, this information can be useful to optimize waste package design for SRP waste glass and to provide data for predicting long-term performance and subsequent conformance to regulations. The repository simulation tests also help to bridge the gap in interpreting results derived from tests performed under the control of the laboratory to the uncertainity and variability of field tests. In these experiments, site-specific repository components and conditions are emphasized and only the site specific materials contact the waste forms. An important feature of these tests is that both actual and simulated waste glasses are tested identically. 7 figures, 2 tables

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.

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.

Coupling fuel cycles with repositories: how repository institutional choices may impact fuel cycle design

International Nuclear Information System (INIS)

Forsberg, C.; Miller, W.F.

2013-01-01

The historical repository siting strategy in the United States has been a top-down approach driven by federal government decision making but it has been a failure. This policy has led to dispatching fuel cycle facilities in different states. The U.S. government is now considering an alternative repository siting strategy based on voluntary agreements with state governments. If that occurs, state governments become key decision makers. They have different priorities. Those priorities may change the characteristics of the repository and the fuel cycle. State government priorities, when considering hosting a repository, are safety, financial incentives and jobs. It follows that states will demand that a repository be the center of the back end of the fuel cycle as a condition of hosting it. For example, states will push for collocation of transportation services, safeguards training, and navy/private SNF (Spent Nuclear Fuel) inspection at the repository site. Such activities would more than double local employment relative to what was planned for the Yucca Mountain-type repository. States may demand (1) the right to take future title of the SNF so if recycle became economic the reprocessing plant would be built at the repository site and (2) the right of a certain fraction of the repository capacity for foreign SNF. That would open the future option of leasing of fuel to foreign utilities with disposal of the SNF in the repository but with the state-government condition that the front-end fuel-cycle enrichment and fuel fabrication facilities be located in that state

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.

2014-01-01

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. PMID:25243063

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.

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

CERN Multimedia

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

Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention

Directory of Open Access Journals (Sweden)

Philipp Baumeister

2012-01-01

Full Text Available Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

Repository operational criteria analysis

International Nuclear Information System (INIS)

Hageman, J.P.; Chowdhury, A.H.

1992-08-01

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 and impacts of any potential changes to those regulations. The study addresses regulatory criteria related to the preclosure aspects of the geologic repository. The study task developed regulatory concepts or potential repository operational criteria (PROC) based on analysis of a repository's safety functions and other regulations for similar facilities. These regulatory concepts or PROC were used as a basis to assess the sufficiency and adequacy of the current criteria in 10 CFR Part 60. Where the regulatory concepts were same as current operational criteria, these criteria were referenced. The operations criteria referenced or the PROC developed are given in this report. Detailed analyses used to develop the regulatory concepts and any necessary PROC for those regulations that may require a minor change are also presented. The results of the ROC task showed a need for further analysis and possible major rule change related to the design bases of a geologic repository operations area, siting, and radiological emergency planning

Consortial routes to effective repositories

OpenAIRE

Moyle, M.; Proudfoot, R.

2009-01-01

A consortial approach to the establishment of repository services can help a group of Higher Education Institutions (HEIs) to share costs, share technology and share expertise. Consortial repository work can tap into existing structures, or it can involve new groupings of institutions with a common interest in exploring repository development. This Briefing Paper outlines some of the potential benefits of collaborative repository activity, and highlights some of the technical and organisation...

Repository design

Energy Technology Data Exchange (ETDEWEB)

John, C M

1982-01-01

Various technical issues of radioactive waste design are addressed in this paper. Two approaches to repository design considered herein are: (1) design to minimize the disturbance of the hot rock; and (2) designs that intentionally modify the hot rock to insure better containment of the wastes. The latter designs range from construction of a highly impermeable barrier around a spherical cavern to creating a matrix of tunnels and boreholes to form a cage within which the hydraulic pressure is nearly constant. Examples of these design alternatives are described in some detail. It is concluded that proposed designs for repositories illustrate that performance criteria considered acceptable for such facilities can be met by appropriate site selection and repository engineering. With these technically feasible design concepts, it is also felt that socioeconomic and institutional issues can be better resolved. (BLM)

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/beta-catenin signaling.

Science.gov (United States)

Roy, Hemant K; Kunte, Dhananjay P; Koetsier, Jennifer L; Hart, John; Kim, Young L; Liu, Yang; Bissonnette, Marc; Goldberg, Michael; Backman, Vadim; Wali, Ramesh K

2006-08-01

Polyethylene glycol (PEG) is one of the most potent chemopreventive agents against colorectal cancer; however, the mechanisms remain largely unexplored. In this study, we assessed the ability of PEG to target cyclin D1-beta-catenin-mediated hyperproliferation in the azoxymethane-treated rat model and the human colorectal cancer cell line, HT-29. Azoxymethane-treated rats were randomized to AIN-76A diet alone or supplemented with 5% PEG-8000. After 30 weeks, animals were euthanized and biopsies of aberrant crypt foci and uninvolved crypts were subjected to immunohistochemical and immunoblot analyses. PEG markedly suppressed both early and late markers of azoxymethane-induced colon carcinogenesis (fractal dimension by 80%, aberrant crypt foci by 64%, and tumors by 74%). In both azoxymethane-treated rats and HT-29 cells treated with 5% PEG-3350 for 24 hours, PEG decreased proliferation (45% and 52%, respectively) and cyclin D1 (78% and 56%, respectively). Because beta-catenin is the major regulator of cyclin D1 in colorectal cancer, we used the T-cell factor (Tcf)-TOPFLASH reporter assay to show that PEG markedly inhibited beta-catenin transcriptional activity. PEG did not alter total beta-catenin expression but rather its nuclear localization, leading us to assess E-cadherin expression (a major determinant of beta-catenin subcellular localization), which was increased by 73% and 71% in the azoxymethane-rat and HT-29 cells, respectively. We therefore investigated the effect of PEG treatment on levels of the negative regulator of E-cadherin, SNAIL, and observed a 50% and 75% decrease, respectively. In conclusion, we show, for the first time, a molecular mechanism through which PEG imparts its antiproliferative and hence profound chemopreventive effect.

p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice

Directory of Open Access Journals (Sweden)

Venkateshwar Madka

2013-08-01

Full Text Available The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group were fed control (AIN-76A or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001. A significant decrease in the bladder tumor weights (by 68.6–80.2%, P < .0001 in males and by 36.9–55.3%, P < .0001 in females was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.

Chemopreventive Potential of Powdered Red Wine Pomace Seasonings against Colorectal Cancer in HT-29 Cells.

Science.gov (United States)

Del Pino-García, Raquel; Rivero-Pérez, María D; González-SanJosé, María L; Ortega-Heras, Miriam; García Lomillo, Javier; Muñiz, Pilar

2017-01-11

This study evaluates the antiproliferative and antigenotoxic actions of powdered red wine pomace seasonings (Sk-S, seedless; W-S, whole; Sd-S, seeds). In vitro gastrointestinal digested and colonic fermented fractions of the seasonings were used as cell treatments. Phenolic acids from Sk-S showed the highest bioaccessibility in the small intestine, whereas polyphenols contained in Sd-S might be the most fermentable in the colon. Dietary fiber from Sk-S was the best substrate for short chain fatty acids production by gut microbiota. Colon cancerous (HT-29) cell viability was inhibited by 50% (IC 50 values) at treatment concentrations ranging from 845 (Sk-S) to 1085 (Sd-S) μg/mL prior digestion, but all digested fractions exhibited similar antiproliferative activities (mean IC 50 = 814 μg/mL). Oxidative DNA damage in cells was also attenuated by the treatments (200 μg/mL, 24 h preincubation), with all colonic fermented fractions displaying similar genoprotective action. These results suggest the potential of red wine pomace seasonings as chemopreventive agents in colorectal cancer.

Centralized mouse repositories.

Science.gov (United States)

Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

2012-10-01

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

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

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

1 ALPHA-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent

Science.gov (United States)

2004-09-01

cancer cells. TTT TG. The primer -for the housekeeping gene G3PDH was purchased from ClonTech. The touchdown 3.2. Induction of differentiation of breast...the housekeeping gene The effects of vitamin D analogues as differentiating G3PDH (C) was identical for all the cDNAs, indicating . agents and...control housekeeping gene. "* G. Lazzaro et al. / European Journal of Cancer 36 (2000) 780-786 785 levels of VDR, do not respond to active vitamin D p53

Office of Geologic Repositories quality assurance plan for high-level radioactive waste repositories

International Nuclear Information System (INIS)

1986-08-01

This document sets forth geologic repository program-wide quality assurance program requirements and defines management's quality assurance responsibilities for the Office of Geologic Repositories and its projects. (LM)

Virtual patient repositories--a comparative analysis.

Science.gov (United States)

Küfner, Julia; Kononowicz, Andrzej A; Hege, Inga

2014-01-01

Virtual Patients (VPs) are an important component of medical education. One way to reduce the costs for creating VPs is sharing through repositories. We conducted a literature review to identify existing repositories and analyzed the 17 included repositories in regards to the search functions and metadata they provide. Most repositories provided some metadata such as title or description, whereas other data, such as educational objectives, were less frequent. Future research could, in cooperation with the repository provider, investigate user expectations and usage patterns.

Technology overview of mined repositories

International Nuclear Information System (INIS)

Gimera, R.; Thirumalai, K.

1982-01-01

Mined repositories present an environmentally viable option for permanent disposal of nuclear waste. This paper reviews the state-of-the-art mining technologies and identifies technological issues and developments necessary to mine a repository in basalt. The thermal loading, isolation, and retrieval requirements of a repository present unique technological challenges unknown to conventional mining practice. The technology issues and developments required in the areas of excavation, roof and ground support, equipment development, instrumentation development, and sealing are presented. Performance assessment methods must be developed to evaluate the adequacies of technologies developed to design, construct, operate, and decommission a repository. A stepwise test-and-development approach is used in the Basalt Waste Isolation Project to develop cost-effective technologies for a repository

Breast Cancer Tissue Repository

National Research Council Canada - National Science Library

Iglehart, J

1997-01-01

The Breast Tissue Repository at Duke enters its fourth year of finding. The purpose of the Repository at Duke is to provide substantial quantities of frozen tissue for explorative molecular studies...

Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

Science.gov (United States)

Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

2008-11-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

Repository Subsurface Preliminary Fire Hazard Analysis

International Nuclear Information System (INIS)

Logan, Richard C.

2001-01-01

This fire hazard analysis identifies preliminary design and operations features, fire, and explosion hazards, and provides a reasonable basis to establish the design requirements of fire protection systems during development and emplacement phases of the subsurface repository. This document follows the Technical Work Plan (TWP) (CRWMS M and O 2001c) which was prepared in accordance with AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''; Attachment 4 of AP-ESH-008, ''Hazards Analysis System''; and AP-3.11Q, ''Technical Reports''. The objective of this report is to establish the requirements that provide for facility nuclear safety and a proper level of personnel safety and property protection from the effects of fire and the adverse effects of fire-extinguishing agents

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.

Cloud Computing and Multi Agent System to improve Learning Object Paradigm

Directory of Open Access Journals (Sweden)

Ana B. Gil

2015-05-01

Full Text Available The paradigm of Learning Object provides Educators and Learners with the ability to access an extensive number of learning resources. To do so, this paradigm provides different technologies and tools, such as federated search platforms and storage repositories, in order to obtain information ubiquitously and on demand. However, the vast amount and variety of educational content, which is distributed among several repositories, and the existence of various and incompatible standards, technologies and interoperability layers among repositories, constitutes a real problem for the expansion of this paradigm. This study presents an agent-based architecture that uses the advantages provided by Cloud Computing platforms to deal with the open issues on the Learning Object paradigm.

INSTITUTIONAL REPOSITORY: EMPLOYMENT IN EDUCATION

Directory of Open Access Journals (Sweden)

Vasyl P. Oleksyuk

2012-11-01

Full Text Available The article investigated the concept of «institutional repository» and determined the aspects of institutional repositories in higher education. Institutional Repositories are information systems that allow preserving, storing and disseminating scientific knowledge produced in higher education and scientific research institutions. This study presented the main aspects using institutional repositories in educational process (such as storage of scientific and educational information, means of organization activity of students, object of studying. This article produced the structure of communities and collections of the institutional. It is described the experience of implementing of DSpace in the learning process.

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.

Desiderata for healthcare integrated data repositories based on architectural comparison of three public repositories.

Science.gov (United States)

Huser, Vojtech; Cimino, James J

2013-01-01

Integrated data repositories (IDRs) are indispensable tools for numerous biomedical research studies. We compare three large IDRs (Informatics for Integrating Biology and the Bedside (i2b2), HMO Research Network's Virtual Data Warehouse (VDW) and Observational Medical Outcomes Partnership (OMOP) repository) in order to identify common architectural features that enable efficient storage and organization of large amounts of clinical data. We define three high-level classes of underlying data storage models and we analyze each repository using this classification. We look at how a set of sample facts is represented in each repository and conclude with a list of desiderata for IDRs that deal with the information storage model, terminology model, data integration and value-sets management.

Process mining software repositories

NARCIS (Netherlands)

Poncin, W.; Serebrenik, A.; Brand, van den M.G.J.

2011-01-01

Software developers' activities are in general recorded in software repositories such as version control systems, bug trackers and mail archives. While abundant information is usually present in such repositories, successful information extraction is often challenged by the necessity to

The Ec prototype repository project: implications of assessments for refining repository design

International Nuclear Information System (INIS)

Svemar, C.

2004-01-01

The most important issue in the evaluation of the repository performance is the long term safety of the repository. Analyses for this issue focuses on the 'steady state' conditions which start at the time when the repository has been saturated and the groundwater table returned to its normal level. The bentonite buffer around the canisters is saturated and homogeneous, and the canister is located exactly in the centre of the buffer. The backfill in the tunnel has been saturated as well and fills the earlier open spaces in the tunnel completely. The task of the activities taking places prior to the start of the 'steady state' conditions, like excavation, deposition, backfilling and sealing, with due consideration to the processes a consequences they may cause in the long run, is to provide for these 'ideal' conditions, as close as possible. While studying these activities in detail it has become obvious that development of methods and techniques needs to be carefully addressed before the decision is made on how to apply them in the repository. One general finding is that the situation in engineering of details is not that much different from the situation in geological characterisation of a site in detail; one more detail of engineering and the consequences it brings often complicates the situation rather than supports the solution prioritized so far. Many of the practical issues have been studied in the Prototype Repository project in the AEspoe Hard Rock Laboratory (Pusch et al., 2000). The Prototype Repository consists of two sections with four respectively two deposition holes with bentonite buffer and canister, the latter holding electrical heaters. The sections are separated by a concrete plug, and the whole test is to be separated from the rest of the laboratory by an outer plug. The project has two objectives: 1. To demonstrate the integrated function of tile deep repository components under realistic conditions and to compare results with models and

48 CFR 227.7108 - Contractor data repositories.

Science.gov (United States)

2010-10-01

... repositories. 227.7108 Section 227.7108 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... Technical Data 227.7108 Contractor data repositories. (a) Contractor data repositories may be established when permitted by agency procedures. The contractual instrument establishing the data repository must...

Rock support for nuclear waste repositories

International Nuclear Information System (INIS)

Abramson, L.W.; Schmidt, B.

1984-01-01

The design of rock support for underground nuclear waste repositories requires consideration of special construction and operation requirements, and of the adverse environmental conditions in which some of the support is placed. While repository layouts resemble mines, design, construction and operation are subject to quality assurance and public scrutiny similar to what is experienced for nuclear power plants. Exploration, design, construction and operation go through phases of review and licensing by government agencies as repositories evolve. This paper discusses (1) the various stages of repository development; (2) the environment that supports must be designed for; (3) the environmental effects on support materials; and (4) alternative types of repository rock support

National Radwaste Repository Mochovce

International Nuclear Information System (INIS)

2000-01-01

In this leaflet the National Radioactive Waste Repository in Mochovce (Repository) is described. The Mochovce National Radioactive Waste Repository is a surface multi-barrier type storage facility for solid and treated solidified radioactive wastes generated from the Slovak Republic nuclear power plants operation and decommissioning, research institutes, laboratories and hospitals. The Repository comprises a system of single- and double-row storage boxes. The first double-row is enclosed by a steel-structure building. The 18 x 6 x 5.5 m storage boxes are made of reinforced concrete. The wall thickness is 600 mm. Two-double-rows, i.e. 80 storage boxes were built as part of Stage I (1 row = 20 storage boxes). Each storage box has a storage capacity of 90 fibre concrete containers of 3.1 m 3 volume. The total storage capacity is 7200 containers with the overall storage volume of 22320 m 3

Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

Science.gov (United States)

Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

2017-01-01

Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

Analysis of Turkey’s Institutional Open Repositories: An Example of Dokuz Eylül University Institutional Open Repository

Directory of Open Access Journals (Sweden)

Korhan Levent Ertürk

2012-03-01

Full Text Available After the declaration of the Budapest Open Access Initiative in 2001, institutional open repositories are known as the most important tool of the self archiving, which is also known as green road. There are 26 institutional repositories, which are all compatible to international standards. All the institutional open repositories of Turkey mentioned before are listed in international open archive directories. In this study institutional open repository of Dokuz Eylül University is examined and institutional open repositories of Turkey are discussed.

Radioactive waste repository of high ecological safety

International Nuclear Information System (INIS)

Sobolev, I.; Barinov, A.; Prozorov, L.

2000-01-01

With the purpose to construct a radioactive waste repository of high ecological safety and reliable containment, MosNPO 'Radon' specialists have developed an advanced type repository - large diameter well (LBD) one. A project is started for the development of a technology for LDW repository construction and pilot operation of the new repository for 25-30 years. The 2 LDW repositories constructed at the 'Radon' site and the developed monitoring system are described

Consistency analysis of network traffic repositories

NARCIS (Netherlands)

Lastdrager, Elmer; Lastdrager, E.E.H.; Pras, Aiko

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

Sellafield repository design concept

International Nuclear Information System (INIS)

1998-01-01

Between 1989 and 1997, UK Nirex Ltd carried out a programme of investigations to evaluate the potential of a site adjacent to the BNFL Sellafield works to host a deep repository for the United Kingdom's intermediate-level and certain low-level radioactive waste. The programme of investigations was wound down following the decision in March 1997 to uphold the rejection of the Company's planning application for the Rock Characterisation Facility (RCF), an underground laboratory which would have allowed further investigations to confirm whether or not the site would be suitable. Since that time, the Company's efforts in relation to the Sellafield site have been directed towards documenting and publishing the work carried out. The design concept for a repository at Sellafield was developed in parallel with the site investigations through an iterative process as knowledge of the site and understanding of the repository system performance increased. This report documents the Sellafield repository design concept as it had been developed, from initial design considerations in 1991 up to the point when the RCF planning application was rejected. It shows, from the context of a project at that particular site, how much information and experience has been gained that will be applicable to the development of a deep waste repository at other potential sites

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.

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.

The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

Directory of Open Access Journals (Sweden)

Yi-Nong Niu

2016-01-01

Full Text Available In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3 cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3 mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun−/− fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride′s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

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

National Research Council Canada - National Science Library

Hakim, Iman

2004-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

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

National Research Council Canada - National Science Library

Hakim, Iman A

2006-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

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

National Research Council Canada - National Science Library

Hakim, Iman A

2005-01-01

.... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

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

National Research Council Canada - National Science Library

Hakim, Iman A

2008-01-01

.... We are conducting a 6-month randomized controlled double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

Nuclear waste repository design and construction

International Nuclear Information System (INIS)

Bohlke, B.M.; Monsees, J.E.

1987-01-01

Extensive underground excavation will be required for construction of a mined geologic repository for nuclear waste. Hundreds of thousands of feet of drift will be required based on the conceptual layout design for each candidate nuclear waste repository. Comparison of boring and blasting excavation methods are discussed, as are special design and construction requirements (e.g., quality assurance procedures and performance assessment) for the nuclear waste repository. Comparisons are made between boring and blasting construction methods for the repository designs proposed for salt, volcanic tuff, and basalt

Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

Science.gov (United States)

Mocellin, Simone; Pilati, Pierluigi; Briarava, Marta; Nitti, Donato

2016-02-01

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For

Analysis of Technical Status on the Application of Cementitious Materials for Radwaste Repository

International Nuclear Information System (INIS)

Kim, Jin Seop; Kwon, Sang Ki; Cho, Won Jin

2008-12-01

In this report, technical status on the application of cementitious materials and related research trends in Sweden, Switzerland and Japan etc. is listed based on the example of ONKALO in Finland. SKB and POSIVA have defined a pH limit ≤ 11 for cement grout leachates. To attain this pH, blending agents must comprise at least 50 wt % of dry materials. Because low pH cement has little, or no free portlandite, the cement consists predominantly of calcium silicate hydrate(CSH) gel with a Ca/Si ratio ≤ 0.8(Savage D. 2007). Silica fume as a blending agent is considered to be most promising for repository low-pH grouts. When adding silica fume to enhance cement quality, it demands high water content in cement paste. Then it is necessary to use additives such as superplasticiser to improve the workability of low-pH cement. Posiva, SKB and NUMO co-operated in developing low-pH grouts for deep repositories 2002-2005. Additionally, it is needed to study more about long-term performance characteristics, interaction of bentonite buffer material with high pH plume, influence on the migration/sorption of radionuclides and their performance numerical modeling. In this regards, international co-research projects such as ESDRED and IAEA CRP are being actively performed

National radioactive wasterRepository Mochovce

International Nuclear Information System (INIS)

2000-01-01

In this leaflet the scheme of the Mochovce National radioactive waste repository for the Slovak Republic is presented. The National radioactive waste repository in Mochovce is a surface type storage facility. It is intended for final disposal of solid and solidified low and intermediate radioactive waste produced during the operation of nuclear power plants and institutions located within the territory of the Slovak Republic. The Repository site is situated about 2 km northwest to the Mochovce NPP

Reverse screening methods to search for the protein targets of chemopreventive compounds

Science.gov (United States)

Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

2018-05-01

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and

Biological Web Service Repositories Review.

Science.gov (United States)

Urdidiales-Nieto, David; Navas-Delgado, Ismael; Aldana-Montes, José F

2017-05-01

Web services play a key role in bioinformatics enabling the integration of database access and analysis of algorithms. However, Web service repositories do not usually publish information on the changes made to their registered Web services. Dynamism is directly related to the changes in the repositories (services registered or unregistered) and at service level (annotation changes). Thus, users, software clients or workflow based approaches lack enough relevant information to decide when they should review or re-execute a Web service or workflow to get updated or improved results. The dynamism of the repository could be a measure for workflow developers to re-check service availability and annotation changes in the services of interest to them. This paper presents a review on the most well-known Web service repositories in the life sciences including an analysis of their dynamism. Freshness is introduced in this paper, and has been used as the measure for the dynamism of these repositories. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

The influence of organic materials on the near field of an intermediate level radioactive waste repository

International Nuclear Information System (INIS)

Wilkins, J.D.

1988-01-01

The influence of organic materials which are present in some intermediate level wastes on the chemistry of the near field of a radioactive waste repository is discussed. Particular attention is given to the possible formation of water soluble complexing agents as a result of the radiation field and chemical conditions. The present state of the research is reviewed. (author)

IAEA safeguards for geological repositories

International Nuclear Information System (INIS)

Moran, B.W.

2005-01-01

In September. 1988, the IAEA held its first formal meeting on the safeguards requirements for the final disposal of spent fuel and nuclear material-bearing waste. The consensus recommendation of the 43 participants from 18 countries at this Advisory Group Meeting was that safeguards should not terminate of spent fuel even after emplacement in, and closure of, a geologic repository.' As a result of this recommendation, the IAEA initiated a series of consultants' meetings and the SAGOR Programme (Programme for the Development of Safeguards for the Final Disposal of Spent Fuel in Geologic Repositories) to develop an approach that would permit IAEA safeguards to verify the non-diversion of spent fuel from a geologic repository. At the end of this process, in December 1997, a second Advisory Group Meeting, endorsed the generic safeguards approach developed by the SAGOR Programme. Using the SAGOR Programme results and consultants' meeting recommendations, the IAEA Department of Safeguards issued a safeguards policy paper stating the requirements for IAEA safeguards at geologic repositories. Following approval of the safeguards policy and the generic safeguards approach, the Geologic Repository Safeguards Experts Group was established to make recommendations on implementing the safeguards approach. This experts' group is currently making recommendations to the IAEA regarding the safeguards activities to be conducted with respect to Finland's repository programme. (author)

Radioactive waste facility as environmental preservation factor; Deposito de rejeitos radioativos como agente de preservacao ambiental

Energy Technology Data Exchange (ETDEWEB)

Heilbron Filho, P.F.L.; Xavier, Ana Maria [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)

1997-12-31

The objective of this article is to show, in a resumed way, the many aspects involved in the selection, licensing and construction of a repository for the safe disposal of low and intermediate radioactive level wastes in Brazil where from we conclude that a repository is for sure an agent of environmental preservation. (author) 22 refs., 9 figs., 9 tabs.; e-mail: paulo at cnen.gov.br

Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.

Science.gov (United States)

Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

2017-06-01

After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

Natural chemopreventive alternatives in oral cancer chemoprevention.

Science.gov (United States)

Scrobota, I; Bolfa, P; Filip, A G; Catoi, C; Alb, C; Pop, O; Tatomir, C; Baciut, G

2016-02-01

We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia

Repository site characterization

International Nuclear Information System (INIS)

Voss, J.W.; Pentz, D.L.

1987-01-01

The characterization of candidate repository sites has a number of programmatic objectives. Principal among these is the acquisition of data: a) to determine the suitability of a site relative to the DOE repository siting guidelines, b) to support model development and calculations to determine the suitability of a site relative to the post closure criteria of the NRC and EPA, c) to support the design of a disposal system, including the waste package and the engineered barrier system, as well as the shafts and underground openings of the repository. In meeting the gaols of site characterization, the authors have an obligation to conduct their investigations within an appropriate budget and schedule. This mandates that a well-constructed and systematic plan for field investigations be developed. Such a plan must fully account for the mechanisms which will control the radiologic performance in the repository. The plan must also flexibly and dynamically respond to the results of each step of field investigation, responding to the spatial variability of earth as well as to enhanced understandings of the performance of the disposal system. Such a plan must ensure that sufficient data are available to support the necessary probabilistic calculations of performance. This paper explores the planning for field data acquisition with specific reference to requirements for demonstrations of the acceptable performance for disposal systems

Chemoprevention of cancer: an ongoing saga.

Science.gov (United States)

Kellen, J A

1999-01-01

The trivial adage "an ounce of prevention..." is certainly appropriate in oncology; cancer has and continues to have an enormous impact on morbidity, suffering, socioeconomics and mortality. Curative therapy is elusive--cancer remains a mainly lethal disease, which makes the objective of prevention even more important and attractive. Sober estimates put the potentially avoidable or preventable cancers in the Western World at 80% (1): the effects of smoking and alcohol, being overweight, diet promiscuity and other lifestyle choices are well known, yet at the individual level, corrective measures are disappointingly ignored. Lately, this issue is being further weakened by our acceptance of inherited susceptibility--why change our habits and indulgences, if we can not escape our genetic destiny? However, there is a massive and growing amount of information on chemoprevention which needs to be carefully evaluated, in the hope that someday, we should be able to avoid or at least delay cancer by the use of natural or synthetic compounds which intervene in the early precancerous process.

Gas generation in repositories

International Nuclear Information System (INIS)

Biddle, P.; Rees, J.H.; McGahan, D.; Rushbrook, P.E.

1987-09-01

The nature and quantities of gases likely to be produced by various processes in repositories for low level and intermediate level radioactive wastes are examined in this preliminary study. Many simplifying assumptions are made where published or experimental data is unavailable. The corrosion of the canisters and metallic components in wastes is likely to be the major gas production process in both types of repository. A significant contribution from microbiological activity is expected to occur in low level repositories, predominantly where no cement grouting of the cans has been carried out. A number of areas for further research, required before a more comprehensive study could be carried out, have been identified. (author)

SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

International Nuclear Information System (INIS)

Randle, D.C.

2000-01-01

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 andC) 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 andC and will typically be integrated over a data communications network throughout the subsurface facility. The subsurface I andC 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 andC 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

Qualifying concrete for a low-level waste repository

International Nuclear Information System (INIS)

Philipose, K.E.

1990-06-01

A waste repository for the belowground disposal of low-level radioactive waste, labelled IRUS (Intrusion Resistant Underground Structure), is planned at Chalk River Nuclear Laboratories. It relies greatly on the durability of concrete for a minimum of 500 years of service life. A research program based on laboratory testing to design a durable concrete and predict its useful engineered service life is in progress. Durability of concrete depends on its resistance of deterioration from both internal and external causes. Since the rate of degradation depends to a major extent on the rate of ingress of aggressive ions into concrete, laboratory testing is in progress to establish the diffusion rates of ions, especially chlorides, sulphate and carbonate ions. A total of 1000 concrete specimens and 500 paste specimens are being exposed at 22 and 45 degrees C to twenty-five different combinations of corrosive agents, including CO 2 . Procedures to measure the ionic profile and to determine the factors controlling diffusion of ions in the various concretes have been developed. The paper presents the initial results from the research program and the longevity predictions to qualify concretes for the IRUS waste repository, based on twelve months of diffusion testing on laboratory specimens

Preliminary design of the repository. Stage 2

International Nuclear Information System (INIS)

Saanio, T.; Kirkkomaeki, T.; Keto, P.; Kukkola, T.; Raiko, H.

2007-04-01

Spent nuclear fuel from Finnish nuclear power plants will be disposed of in deep bedrock in Olkiluoto, Eurajoki. The repository is planned to be excavated at a depth of 400 - 500 metres. Access routes to the repository include a 1:10 inclined access tunnel, and vertical shafts. The fuel is encapsulated in the encapsulation plant above ground and transferred to the repository in the canister lift. Deposition tunnels, central tunnels and technical rooms are excavated at the disposal level. The canisters are deposited in deposition holes that are covered with bentonite blocks. The deposition holes are bored in the floors of the deposition tunnels. The central tunnel system consists of two parallel central tunnels that are inter-connected at certain distances. Two parallel central tunnels improve the fire safety of the rooms and also allow flexible backfilling and closing of the deposition tunnels in stages at the operational phase of the repository. An underground rock characterization facility, ONKALO, is excavated at the disposal level to support and confirm investigations carried out from above ground. ONKALO is designed so that it can later serve as part of the repository. ONKALO excavations were started in 2004. The repository will be excavated in the 2010s and operation will start in 2020. The fifth nuclear power unit makes the operational phase of the repository very long. Parts of the repository will be excavated and closed over the long operational period. The repository can be constructed at one or several levels. The one-storey alternative is the so-called reference alternative in this preliminary design report. The two-storey alternative is also taken into account in the ONKALO designs. The preliminary designs of the repository are presented as located in Olkiluoto. The location of the repository will be revised when more information on the bedrock has been gained. More detailed data of the circumstances will be obtained from above ground investigations

Preliminary design of the repository, stage 2

International Nuclear Information System (INIS)

Saanio, T.; Kirkkomaeki, T.; Keto, P.; Kukkola, T.; Raiko, H.

2007-01-01

Spent nuclear fuel from Finnish nuclear power plants will be disposed of in deep bedrock in Olkiluoto, Eurajoki. The repository is planned to be excavated at a depth of 400 - 500 metres. Access routes to the repository include a 1:10 inclined access tunnel, and vertical shafts. The fuel is encapsulated in the encapsulation plant above ground and transferred to the repository in the canister lift. Deposition tunnels, central tunnels and technical rooms are excavated at the disposal level. The canisters are deposited in deposition holes that are covered with bentonite blocks. The deposition holes are bored in the floors of the deposition tunnels. The central tunnel system consists of two parallel central tunnels that are inter-connected at certain distances. Two parallel central tunnels improve the fire safety of the rooms and also allow flexible backfilling and closing of the deposition tunnels in stages at the operational phase of the repository. An underground rock characterization facility, ONKALO, is excavated at the disposal level to support and confirm investigations carried out from above ground. ONKALO is designed so that it can later serve as part of the repository. ONKALO excavations were started in 2004. The repository will be excavated in the 2010s and operation will start in 2020. The fifth nuclear power unit makes the operational phase of the repository very long. Parts of the repository will be excavated and closed over the long operational period. The repository can be constructed at one or several levels. The one-storey alternative is the so-called reference alternative in this preliminary design report. The two-storey alternative is also taken into account in the ONKALO designs. The preliminary designs of the repository are presented as located in Olkiluoto. The location of the repository will be revised when more information on the bedrock has been gained. More detailed data of the circumstances will be obtained from above ground investigations

Nuclear waste repository siting

International Nuclear Information System (INIS)

Soloman, B.D.; Cameron, D.M.

1987-01-01

This paper discusses the geopolitics of nuclear waste disposal in the USA. Constitutional choice and social equity perspectives are used to argue for a more open and just repository siting program. The authors assert that every potential repository site inevitably contains geologic, environmental or other imperfections and that the political process is the correct one for determining sites selected

Granite-repository - geochemical environment

International Nuclear Information System (INIS)

1979-04-01

Some geochemical data of importance for a radioactive waste repository in hard rock are reviewed. The ground water composition at depth is assessed. The ground water chemistry in the vicinity of uranium ores is discussed. The redox system in Swedish bedrock is described. Influences of extreme climatic changes and of repository mining and construction are also evaluated

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.

Safeguards for geological repositories

International Nuclear Information System (INIS)

Fattah, A.

2000-01-01

Direct disposal of spent nuclear fuel in geological repositories is a recognised option for closing nuclear fuel cycles. Geological repositories are at present in stages of development in a number of countries and are expected to be built and operated early next century. A State usually has an obligation to safely store any nuclear material, which is considered unsuitable to re-enter the nuclear fuel cycle, isolated from the biosphere. In conjunction with this, physical protection has to be accounted for to prevent inadvertent access to such material. In addition to these two criteria - which are fully under the State's jurisdiction - a third criterion reflecting international non-proliferation commitments needs to be addressed. Under comprehensive safeguards agreements a State concedes verification of nuclear material for safeguards purposes to the IAEA. The Agency can thus provide assurance to the international community that such nuclear material has been used for peaceful purposes only as declared by the State. It must be emphasised that all three criteria mentioned constitute a 'unit'. None can be sacrificed for the sake of the other, but compromises may have to be sought in order to make their combination as effective as possible. Based on comprehensive safeguards agreements signed and ratified by the State, safeguards can be terminated only when the material has been consumed or diluted in such a way that it can no longer be utilised for any nuclear activities or has become practicably irrecoverable. As such safeguards for nuclear material in geological repositories have to be continued even after the repository has been back-filled and sealed. The effective application of safeguards must assure continuity-of-knowledge that the nuclear material in the repository has not been diverted for an unknown purpose. The nuclear material disposed in a geological repository may eventually have a higher and long term proliferation risk because the inventory is

Modelling saline intrusion for repository performance assessment

International Nuclear Information System (INIS)

Jackson, C.P.

1989-04-01

UK Nirex Ltd are currently considering the possibility of disposal of radioactive waste by burial in deep underground repositories. The natural pathway for radionuclides from such a repository to return to Man's immediate environment (the biosphere) is via groundwater. Thus analyses of the groundwater flow in the neighbourhood of a possible repository, and consequent radionuclide transport form an important part of a performance assessment for a repository. Some of the areas in the UK that might be considered as possible locations for a repository are near the coast. If a repository is located in a coastal region seawater may intrude into the groundwater flow system. As seawater is denser than fresh water buoyancy forces acting on the intruding saline water may have significant effects on the groundwater flow system, and consequently on the time for radionuclides to return to the biosphere. Further, the chemistry of the repository near-field may be strongly influenced by the salinity of the groundwater. It is therefore important for Nirex to have a capability for reliably modelling saline intrusion to an appropriate degree of accuracy in order to make performance assessments for a repository in a coastal region. This report describes work undertaken in the Nirex Research programme to provide such a capability. (author)

Analisis Konten dan Kebijakan Akses Institutional Repository

Directory of Open Access Journals (Sweden)

Amirul Ulum

2016-07-01

Abstract; Institutional repository has become a major concern of higher education in Indonesia. The number of institutional respository was increased, one of the reason is the ranking web of repositories has been conducted by the Cybermetrics Lab in 2008. At that time, many institutions started to build institutional repository in order to manage the scientific work and also trying to reach the better ranks. Meanwhile, it is an achievement of institution performance which can be promote and increase visibility for the institution. University of Surabaya has also developed the institutional repository and managed by the library. The aims of this study is to analyze the content availability and access policies defined by the University of Surabaya repository  providing services to the academic community and external users. The method used in this study by using observations of the institutional repository University of Surabaya with a literature review to clarify the analysis of the content and access policies. The results of this study indicate that the library's role is has the authority to manage the scientific work of academic community can be done through the institutional repository. However there is still need for library to be proactive to communicate regulations on mandatory deposit of scientific work and create intensive promotion of the institutional repository.

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

2011-01-01

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. While 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. While 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, while 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 demonstrate 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 appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

Process model repositories and PNML

NARCIS (Netherlands)

Hee, van K.M.; Post, R.D.J.; Somers, L.J.A.M.; Werf, van der J.M.E.M.; Kindler, E.

2004-01-01

Bringing system and process models together in repositories facilitates the interchange of model information between modelling tools, and allows the combination and interlinking of complementary models. Petriweb is a web application for managing such repositories. It supports hierarchical process

Radioactive waste repository study

International Nuclear Information System (INIS)

1978-11-01

This is the second part of a report of a preliminary study for AECL. It considers the requirements for an underground waste repository for the disposal of wastes produced by the Canadian Nuclear Fuel Program. The following topics are discussed with reference to the repository: 1) geotechnical assessment, 2) hydrogeology and waste containment, 3) thermal loading and 4) rock mechanics. (author)

Open DOAR the Directory of Open Access Repositories

CERN Multimedia

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...

Evaluasi Website Repositori Institusi Universitas Surabaya

Directory of Open Access Journals (Sweden)

Amirul Ulum

2015-11-01

Full Text Available The  development  of  institutional  repositories  (IRs  in Indonesia within the broader framework of open access has significant impact on preserving intellectual capital and scholarly communication. Institutional  repositories  play  a  fundamental  role  in  centralizing, preserving,  and  making  accessible  institution’s  intellectual  capital. Evaluation of the system is to determine the functionality the system to meet the users need. Using a descriptive analysis this study wants to evaluate institutional repositories of University of Surabaya. The result is usefull for institution to develop the repository systems.

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

Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

Directory of Open Access Journals (Sweden)

Sazal Patyar

2017-01-01

Full Text Available Artesunate (ART is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6: Group I - vehicle (1 mM ethylenediaminetetraacetic acid, Group II - DMH (20 mg/kg, Group III - DMH + 5-fluorouracil (81 mg/kg, Group IV - DMH + ART (6.7 mg/kg. After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO, antioxidant status, average number of aberrant crypt foci (ACF, and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

Trial endpoints for drug approval in oncology: Chemoprevention.

Science.gov (United States)

Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

Selenium Supranutrition: Are the Potential Benefits of Chemoprevention Outweighed by the Promotion of Diabetes and Insulin Resistance?

Science.gov (United States)

Rocourt, Caroline R. B.; Cheng, Wen-Hsing

2013-01-01

Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. PMID:23603996

Alternative measure for performance of HLW geologic repository

International Nuclear Information System (INIS)

Joonhang, Ahn; Chambre, P.L.

2001-01-01

A repository performance model that can show effects of canister multiplicity and repository configuration has been developed. Masses of a radionuclide in the repository and in the far field are proposed as performance measures. Canister multiplicity has significant effects on the release of long-lived radionuclides from the repository. As more canisters are included in the same water stream, the radionuclide concentration in the stream increases, but becomes independent of the number of canisters for sufficiently many canisters. Effects of reduction of radionuclide mass in the repository on the repository performance are clearly observed if the canister multiplicity is taken into account and the mass-based measures are applied. (author)

Accelerator Physics Code Web Repository

CERN Document Server

Zimmermann, Frank; Bellodi, G; Benedetto, E; Dorda, U; Giovannozzi, Massimo; Papaphilippou, Y; Pieloni, T; Ruggiero, F; Rumolo, G; Schmidt, F; Todesco, E; Zotter, Bruno W; Payet, J; Bartolini, R; Farvacque, L; Sen, T; Chin, Y H; Ohmi, K; Oide, K; Furman, M; Qiang, J; Sabbi, G L; Seidl, P A; Vay, J L; Friedman, A; Grote, D P; Cousineau, S M; Danilov, V; Holmes, J A; Shishlo, A; Kim, E S; Cai, Y; Pivi, M; Kaltchev, D I; Abell, D T; Katsouleas, Thomas C; Boine-Frankenheim, O; Franchetti, G; Hofmann, I; Machida, S; Wei, J

2006-01-01

In the framework of the CARE HHH European Network, we have developed a web-based dynamic acceleratorphysics code repository. We describe the design, structure and contents of this repository, illustrate its usage, and discuss our future plans, with emphasis on code benchmarking.

ACCELERATION PHYSICS CODE WEB REPOSITORY.

Energy Technology Data Exchange (ETDEWEB)

WEI, J.

2006-06-26

In the framework of the CARE HHH European Network, we have developed a web-based dynamic accelerator-physics code repository. We describe the design, structure and contents of this repository, illustrate its usage, and discuss our future plans, with emphasis on code benchmarking.

Consistency of Network Traffic Repositories: An Overview

NARCIS (Netherlands)

Lastdrager, E.; Lastdrager, E.E.H.; Pras, Aiko

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

48 CFR 227.7207 - Contractor data repositories.

Science.gov (United States)

2010-10-01

... repositories. 227.7207 Section 227.7207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... Computer Software and Computer Software Documentation 227.7207 Contractor data repositories. Follow 227.7108 when it is in the Government's interests to have a data repository include computer software or to...

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.

Reference repository design concept for bedded salt

International Nuclear Information System (INIS)

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

1980-01-01

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

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.

Hydrothermal conditions around a radioactive waste repository

International Nuclear Information System (INIS)

Thunvik, R.; Braester, C.

1981-12-01

Numerical solutions for the hydrothermal conditions around a hard rock repository for nuclear fuel waste are presented. The objective of the present investigation is to illustrate in principle the effect of heat released from a hypothetical radioactive waste repository with regard to anisotropy in the rock permeability. Permeability and porosity are assumed to be constant or to decrease exponentially with depth. The hypothetical repository is situated below a horizontal ground surface or below the crest of a hill, and it is assumed that the water table follows the topography. Major interest in the analysis is directed towards the influence of anisotropy in the permeability on the flow patterns and travel times for water particles, being traced from the repository to the ground surface. The presented results show that anisotropy in the permeability may have a significant influence on the flow conditions around the repository and subsequently also on the travel times from the repository. (Authors)

Wetting of bituminized ion-exchangers under simulated repository conditions

International Nuclear Information System (INIS)

Aalto, H.; Valkiainen, M.

2001-01-01

According to the present plans the spent nuclear fuel from four Finnish nuclear power units will be transferred after interim storage to the final disposal site where it will be encapsulated and disposed of in a final repository constructed into the bedrock at a depth of 500 meters. Low and medium level waste generated at nuclear power plants will be finally disposed of in caverns constructed in the bedrock at the power plant site. The safety of the final disposal is based on a multibarrier concept and the degree of safety is estimated by using predictive models. The properties of the waste form are taken into account in the design of the repository construction. Bitumen has been chosen as an immobilisation agent for the wet wastes at Olkiluoto Power Plant, where two BWR units, TVO 1 and TVO 2, have separate bituminization facilities designed by Asea-Atom. Properties of bituminized spent ion-exchange resins from Olkiluoto power plant have been studied by VTT Chemical Technology since the late 70's. These studies have concentrated mainly on determining the long-term behaviour of the bituminization product under the repository conditions. Current interest lies on wetted product as a diffusion barrier. For this purpose a microscopic method for the visualisation of the structure of the wetted product has been developed. The equilibration of the samples in simulated concrete groundwater is currently going on at a temperature of 5-8 deg. C. Preliminary results are presented in this paper. Diffusion experiments have been planned for the further characterising of the wetted product as a release barrier for radionuclides including modelling. (author)

Repository operational criteria comparative analysis

International Nuclear Information System (INIS)

Hageman, J.P.; Chowdhury, A.H.

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

A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.

Science.gov (United States)

Kelly, Karen; Kittelson, John; Franklin, Wilbur A; Kennedy, Timothy C; Klein, Catherine E; Keith, Robert L; Dempsey, Edward C; Lewis, Marina; Jackson, Mary K; Hirsch, Fred R; Bunn, Paul A; Miller, York E

2009-05-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The

A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without α Tocopherol or Observation in Subjects at High Risk for Lung Cancer

Science.gov (United States)

Kelly, Karen; Kittelson, John; Franklin, Wilbur A.; Kennedy, Timothy C.; Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.

2011-01-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without α tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus α tocopherol (13-cis RA/α toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment “failure” defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/α toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/α toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36–2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, −0.18; 95% confidence interval, −1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of �

Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

Science.gov (United States)

Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

2012-02-01

Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

What do we mean by a cold repository?

International Nuclear Information System (INIS)

Halsey, W.G.

1994-01-01

The topic of thermal loading of a potential repository at Yucca Mountain in Nevada has been the subject of intense discussion within the project technical community. While terms such as ''Hot Repository'' and ''Cold Repository'' are frequently used, they have not been clearly defined. In particular, the definition of a cold repository has remained the opinion of each individual. This has led to confusion and misunderstanding. In this paper, a number of observed definitions for a cold repository are discussed along with the technical implications, assumptions and inconsistencies. Finally, a common language is suggested

Multi-dimensional transport modelling of corrosive agents through a bentonite buffer in a Canadian deep geological repository.

Science.gov (United States)

Briggs, Scott; McKelvie, Jennifer; Sleep, Brent; Krol, Magdalena

2017-12-01

The use of a deep geological repository (DGR) for the long-term disposal of used nuclear fuel is an approach currently being investigated by several agencies worldwide, including Canada's Nuclear Waste Management Organization (NWMO). Within the DGR, used nuclear fuel will be placed in copper-coated steel containers and surrounded by a bentonite clay buffer. While copper is generally thermodynamically stable, corrosion can occur due to the presence of sulphide under anaerobic conditions. As such, understanding transport of sulphide through the engineered barrier system to the used fuel container is an important consideration in DGR design. In this study, a three-dimensional (3D) model of sulphide transport in a DGR was developed. The numerical model is implemented using COMSOL Multiphysics, a commercial finite element software package. Previous sulphide transport models of the NWMO repository used a simplified one-dimensional system. This work illustrates the importance of 3D modelling to capture non-uniform effects, as results showed locations of maximum sulphide flux are 1.7 times higher than the average flux to the used fuel container. Copyright © 2017. Published by Elsevier B.V.

The influence of organic materials on the near field of an intermediate level waste radioactive waste repository

International Nuclear Information System (INIS)

Wilkins, J.D.

1988-02-01

The influence of organic materials, which are present in some intermediate level wastes, on the chemistry of the near field of a radioactive waste repository is discussed. Particular attention is given to the possible formation of water soluble complexing agents formed as a result of the radiation field and chemical conditions. The present state of the research is reviewed. (author)

Oleuropein and Cancer Chemoprevention: The Link is Hot

Directory of Open Access Journals (Sweden)

Ammad Ahmad Farooqi

2017-04-01

Full Text Available Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.

Radioactive waste repository study

International Nuclear Information System (INIS)

1978-11-01

This is the first part of a report of a preliminary study for Atomic Energy of Canada Limited. It considers the requirements for an underground waste repository for the disposal of wastes produced by the Canadian Nuclear Fuel Program. The following topics are discussed with reference to the repository: 1) underground layout, 2) cost estimates, 3) waste handling, 4) retrievability, decommissioning, sealing and monitoring, and 5) research and design engineering requirements. (author)

MAJOR REPOSITORY DESIGN ISSUES

International Nuclear Information System (INIS)

JACK N. BAILEY, DWAYNE CHESTNUT, JAMES COMPTON AND RICHARD D. SNELL

1997-01-01

The Yucca Mountain Project is focused on producing a four-part viability assessment in late FY98. Its four components (design, performance assessment, cost estimate, and licensing development plan) must be consistent. As a tool to compare design and performance assessment options, a series of repository pictures were developed for the sequential time phases of a repository. The boundaries of the time phases correspond to evolution in the engineered barrier system (EBS)

An analysis of repository waste-handling operations

International Nuclear Information System (INIS)

Dennis, A.W.

1990-09-01

This report has been prepared to document the operational analysis of waste-handling facilities at a geologic repository for high-level nuclear waste. The site currently under investigation for the geologic repository is located at Yucca Mountain, Nye County, Nevada. The repository waste-handling operations have been identified and analyzed for the year 2011, a steady-state year during which the repository receives spent nuclear fuel containing the equivalent of 3000 metric tons of uranium (MTU) and defense high-level waste containing the equivalent of 400 MTU. As a result of this analysis, it has been determined that the waste-handling facilities are adequate to receive, prepare, store, and emplace the projected quantity of waste on an annual basis. In addition, several areas have been identified where additional work is required. The recommendations for future work have been divided into three categories: items that affect the total waste management system, operations within the repository boundary, and the methodology used to perform operational analyses for repository designs. 7 refs., 48 figs., 11 tabs

Memory provisions for the Manche Surface Repository

International Nuclear Information System (INIS)

Dumont, Jean-Noel; Espiet-Subert, Florence

2015-01-01

The French La Manche repository site received its last radioactive waste package in 1994. In 2003, the official surveillance phase of the closed repository started under the supervision of Andra (the national industrial operator), the French Nuclear Safety Authority (ASN) and society (e.g. the local municipalities). Florence Espiet explained that information on the existence of the repository, its content, how it was operated and how it works needs to be preserved. It also is planned to review the information periodically for a minimum of 300 years. She described the creation of two documents on memory (a detailed and a summary one), both on permanent paper, and the preservation of the land registration. The latter constitutes 'passive' provisions for preserving memory. In addition, a number of 'active' provisions are and will be put in place: guided visits, exhibitions, partnerships with organisations dealing with memory preservation, and the creation of a think tank. The latter consists of local citizens and politicians, retired employees from Andra and artists that meet several times a year and reflect on memory preservation from the perspective of, for instance, local history, education, arts and rituals. Finally, two types of markers will be used to preserve the repository's memory: i) three herbaria cataloguing the plants growing on the site of the repository, including a very short description of the repository, will be stored at different sites in France; ii) a stele indicating the main characteristics of the repository, potentially linked to an art work, will be erected at the repository

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

Science.gov (United States)

Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

2010-07-01

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

Mobile agent location in distributed environments

Science.gov (United States)

Fountoukis, S. G.; Argyropoulos, I. P.

2012-12-01

An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

Safety analysis in subsurface repositories

International Nuclear Information System (INIS)

1985-06-01

The development of mathematical models to represent the repository-geosphere-biosphere system, and the development of a structure for data acquisition, processing, and use to analyse the safety of subsurface repositories, are presented. To study the behavior of radionuclides in geosphere a laboratory to determine the hydrodynamic dispersion coefficient was constructed. (M.C.K.) [pt

How many geologic repositories will be needed

International Nuclear Information System (INIS)

Evans, T.J.; Halstead, R.J.

1987-01-01

DOE's postponement of site-specific work on the second repository program had rekindled debate over the number of geologic repositories needed for disposal of high level radioactive waste. The multiple repository approach grew out of the March, 1979 IRG report, which recommended co-disposal of civilian and defense HLW in a system of regional repositories. The multiple repository approach was adopted by DOE, and incorporated in the Nuclear Waste Policy Act passed by Congress in December, 1982. Since the late 1970's, the slower than anticipated growth of the nuclear power industry has substantially reduced earlier estimates of the amount of civilian spent fuel which will require geologic disposal. Reactors currently in operation (78.5 GWe) and reactors in the construction pipeline (28 GWe) are expected to discharge about 103,200 MTU of spent fuel by the year 2036, assuming no increase in fuel burnup rate. By the year 2020, defense high level radioactive wastes equivalent to as much as 27,000 MTU could require geologic disposal. Small amounts of high level waste from other sources will also require geologic disposal. Total disposal requirements appear to be less than 140,000 MTU. The five sites nominated for the first repository, as well as hypothetical sites in granite, the host rock under primary consideration for the second repository, all appear capable of accommodating up to 140,000 MTU

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...

Building Scientific Data's list of recommended data repositories

Science.gov (United States)

Hufton, A. L.; Khodiyar, V.; Hrynaszkiewicz, I.

2016-12-01

When Scientific Data launched in 2014 we provided our authors with a list of recommended data repositories to help them identify data hosting options that were likely to meet the journal's requirements. This list has grown in size and scope, and is now a central resource for authors across the Nature-titled journals. It has also been used in the development of data deposition policies and recommended repository lists across Springer Nature and at other publishers. Each new addition to the list is assessed according to a series of criteria that emphasize the stability of the resource, its commitment to principles of open science and its implementation of relevant community standards and reporting guidelines. A preference is expressed for repositories that issue digital object identifiers (DOIs) through the DataCite system and that share data under the Creative Commons CC0 waiver. Scientific Data currently lists fourteen repositories that focus on specific areas within the Earth and environmental sciences, as well as the broad scope repositories, Dryad and figshare. Readers can browse and filter datasets published at the journal by the host repository using ISA-explorer, a demo tool built by the ISA-tools team at Oxford University1. We believe that well-maintained lists like this one help publishers build a network of trust with community data repositories and provide an important complement to more comprehensive data repository indices and more formal certification efforts. In parallel, Scientific Data has also improved its policies to better support submissions from authors using institutional and project-specific repositories, without requiring each to apply for listing individually. Online resources Journal homepage: http://www.nature.com/scientificdata Data repository criteria: http://www.nature.com/sdata/policies/data-policies#repo-criteria Recommended data repositories: http://www.nature.com/sdata/policies/repositories Archived copies of the list: https

Radioactive Waste Repositories and Incentives to Local Communities

International Nuclear Information System (INIS)

Knapp, A.; Medakovic, S.

2008-01-01

Public acceptance of radioactive waste (RW) repository depends on various and often community-specific factors. Although radiological risk from a properly constructed low and intermediate level waste (LILW) repository is practically negligible, routine safety considerations will favor low populated areas and therefore probably underdeveloped communities. Repository acceptance in such communities is more likely to be facilitated by prospective benefits to local economy, such as infrastructure development and increased employment, as well as by dedicated financial incentives to the community. Direct financial compensation to the local community for acceptance of the repository has been considered in some documents in countries experienced in RW management, but it has not become a widely accepted practice. In Croatia, a possibility for such compensation is mentioned in the land use plan in conjunction with the prospective RW repository site. In Slovenia, the government has already specified the annual amount of 2.33 million euro as a compensation for 'limited land use' to be shared by local communities in the vicinity of the planned LILW repository during its operation. Applicability of the Slovenian compensations to the prospective joint Slovenian-Croatian repository is not yet clear, at least in the aspect of joint funding. The joint Slovenian-Croatian Decommissioning and LILW and SF management program for NPP Krsko from 2004 did conservatively include the compensations into the repository cost estimates, but that might not be retained in subsequent revisions of the Program. According to the agreement between governments of Slovenia and Croatia on the Nuclear power plant Krsko, Croatian side has no obligations to participate in 'public expenditures' introduced after the agreement, as would be the case of community compensations for LILW repository in Slovenia. Before further decisions on joint NPP Krsko waste management are made, including the issue of LILW

Management of radioactive waste at Novi Han Repository

International Nuclear Information System (INIS)

Stefanova, I.G.; Mateeva, M.D.; Milanov, M.V.

2002-01-01

The Novi Han Repository is the only existing repository in Bulgaria for the disposal of radioactive waste from nuclear applications in industry, medicine and research. The repository was constructed in the early sixties according to the existing requirements. It was operated by the Institute for Nuclear Research and Nuclear Energy for more than thirty years without any accident or release of radioactivity to the environment, but without any investment for upgrading. As a consequence, the Bulgarian Nuclear Safety Authority temporarily stopped the operation of the repository in 1994. The measures for upgrading the Novi Han Repository, supported by the IAEA under TC Project BUL/4/005 'Increasing Safety of Novi Han Repository', are presented in this paper. They comprise: assessment of radionuclide inventory and future waste arisings, characterisation of disposal vaults, characterisation of the site, safety assessment, upgrading of the monitoring system, option study for the selection of treatment and conditioning processes and the development of a conceptual design for low and intermediate level waste processing and storage facility, immediate measures for improvement of the existing disposal vaults and infrastructure, construction of above-ground temporary storage structures, and resuming the operation of the Novi Han Repository. The necessary activities for re-licensing of the Novi Han Repository, construction of a waste processing and storage facility and a disposal facility for spent sealed sources are discussed. (author)

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...

Upgrading of radon's type near surface repository in Latvia

International Nuclear Information System (INIS)

Abramenkovs, A.

2006-01-01

In 1959, the Soviet government decided to construct the near surface radioactive wastes repository 'Radons' near the Baldone city. It was put in operation in 1962. The changes in the development of the repository were induced by the necessarily to upgrade it for disposal of radioactive wastes from the decommissioning of the Salaspils Research Reactor (SRR). The safety assessment of repository was performed during 2000-2001 under the PHARE project for necessary upgrades of repository. The outline design for new vaults and interim storage for long lived radioactive wastes was elaborated during 2003-2004 years. The Environmental Impact Assessment (EIA) for upgrade of Baldone repository was performed during 2004-2005 years. It was found, that additional efforts must be devoted for solution of social aspects o for successful operation and upgrade of repository. It was shown by EIA, that the local population has a negative opinion against the upgrade of repository in Latvia. The main recommendations for upgrades were connected with increasing the safety of repository, increasing of PR activities for education of society and developing of compensation mechanism for local municipality. (author)

Selection of Corrosion Resistant Materials for Nuclear Waste Repositories

International Nuclear Information System (INIS)

R.B. Rebak

2006-01-01

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

Numerical modeling of magma-repository interactions

NARCIS (Netherlands)

Bokhove, Onno

2001-01-01

This report explains the numerical programs behind a comprehensive modeling effort of magma-repository interactions. Magma-repository interactions occur when a magma dike with high-volatile content magma ascends through surrounding rock and encounters a tunnel or drift filled with either a magmatic

Multinational/regional repository - an illusion or solution

International Nuclear Information System (INIS)

Mele, I.

2006-01-01

The concept and current status of multinational and regional repositories are presented in the paper. Particular emphasis is given to the results and findings of the recent EU project SAPIERR, investigating the feasibility of regional repository concepts in Europe. Prospects for further development of multinational repositories are also brought forward and the impact and potential benefits of this approach to our national disposal programme are discussed as well. (author)

Repository performance confirmation

International Nuclear Information System (INIS)

Hansen, Francis D.

2011-01-01

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 of the

The Lincoln Repository presentation: ten reasons why you should put a copy of your work in the Repository

OpenAIRE

Stainthorp, Paul

2010-01-01

Slideshow presentation created to promote the Lincoln Repository to staff at the University of Lincoln. Consists of ten reasons why academic authors should consider depositing copies of their work in the Repository.

International perspective on repositories for low level waste

International Nuclear Information System (INIS)

Bergstroem, Ulla; Pers, Karin; Almen, Ylva

2011-12-01

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

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

Data repositories for medical education research: issues and recommendations.

Science.gov (United States)

Schwartz, Alan; Pappas, Cleo; Sandlow, Leslie J

2010-05-01

The authors explore issues surrounding digital repositories with the twofold intention of clarifying their creation, structure, content, and use, and considering the implementation of a global digital repository for medical education research data sets-an online site where medical education researchers would be encouraged to deposit their data in order to facilitate the reuse and reanalysis of the data by other researchers. By motivating data sharing and reuse, investigators, medical schools, and other stakeholders might see substantial benefits to their own endeavors and to the progress of the field of medical education.The authors review digital repositories in medicine, social sciences, and education, describe the contents and scope of repositories, and present extant examples. The authors describe the potential benefits of a medical education data repository and report results of a survey of the Society for Directors of Research in Medicine Education, in which participants responded to questions about data sharing and a potential data repository. Respondents strongly endorsed data sharing, with the caveat that principal investigators should choose whether or not to share data they collect. A large majority believed that a repository would benefit their unit and the field of medical education. Few reported using existing repositories. Finally, the authors consider challenges to the establishment of such a repository, including taxonomic organization, intellectual property concerns, human subjects protection, technological infrastructure, and evaluation standards. The authors conclude with recommendations for how a medical education data repository could be successfully developed.

Implementation of the Brazilian national repository

International Nuclear Information System (INIS)

Tello, Cledola Cassia Oliveira de

2013-01-01

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)

The development of safeguards for geological repositories

International Nuclear Information System (INIS)

Van der Meer, K.

2009-01-01

Traditionally, research and development on geological repositories for High Level Waste (HLW) focuses on the short- and long-term safety aspects of the repository. If the repository will also be used for the disposal of spent fuel, safeguards aspects have to be taken into account. Safety and safeguards requirements may be contradictory; the safety of a geological repository is based on the non-intrusion of the geological containment, while safeguards require regular inspections of position and amount of the spent fuel. Examples to reconcile these contradictory requirements are the use of information required for the safety assessment of the geological repository for safeguards purposes and the adaptation of the safeguards approach to use non-intrusive inspection techniques. The principles of an inspection approach for a geological repository are now generally accepted within the IAEA. The practical applicability of the envisaged inspection techniques is still subject to investigation. It is specifically important for the Belgian situation that an inspection technique can be used in clay, the geological medium in which Belgium intends to dispose its HLW and spent fuel. The work reported in this chapter is the result of an international cooperation in the framework of the IAEA, in which SCK-CEN participates

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

Refinancing of the search for a repository and of the repository for heat generating radioactive Waste. Pt. 2

International Nuclear Information System (INIS)

Moench, Christoph

2013-01-01

Part I of this article, which appeared in the preceding issue, described in general terms the background to the search for a disposal site and the result of the exploration to date of the repository, which would appear to be suitable from a mining standpoint according to the present knowledge. According to the rules in effect up to now, the exploration and construction would be financed by advance payments on the contributions of the waste producing companies, in particular the utility companies. The working draft of an 'Act on the search for and selection of a site for a repository for heat generating radioactive waste' (Gesetz zur Suche und Auswahl eines Standortes fuer ein Endlager fuer waermeentwickelnde radioaktive Abfaelle) from autumn 2012 provides for a new version of section 21b Atomic Energy Act, under which the costs for 'carrying out a repository selection procedure pursuant to the Repository Selection Act (Standort-auswahlgesetz)' would be allocated to the future users of the repository who are obliged to make contributions as a 'necessary expense'. Part II evaluates this provision of the working draft on the basis of the financial constitutional law. A comparison of sites is not a measure that could be allocated to the future users of the repository who are obliged to make contributions as a 'necessary expense'. Moreover, there is a lack of responsibility for the financing and of a legally relevant advantage that would be conferred by a cumulative alternative repository search for the later users of the repository who are obliged to provide the pre-financing. The costs can therefore not be allocated to the later users as either a contribution or a special charge, not even by way of an association with mandatory membership (Zwangsverband). They must be borne by the state. Consequently, the allocation stipulated by provision would constitute an impermissible charge under financial constitutional law. (orig.)

Institutional Repositories as Infrastructures for Long-Term Preservation

Science.gov (United States)

Francke, Helena; Gamalielsson, Jonas; Lundell, Björn

2017-01-01

Introduction: The study describes the conditions for long-term preservation of the content of the institutional repositories of Swedish higher education institutions based on an investigation of how deposited files are managed with regards to file format and how representatives of the repositories describe the functions of the repositories.…

Socioeconomic impacts of repositories

International Nuclear Information System (INIS)

Thomas, J.K.; Hamm, R.R.; Murdock, S.H.

1983-01-01

Federal and state decision makers, community leaders, and residents must know how communities will be changed by the impacts of a high-level nuclear waste repository. This chapter identifies the factors affecting an assessment of socioeconomic impacts and the types of impacts (economic, demographic, fiscal, community service, and social) likely to occur as a result of repository development. Each of these types can be divided into standard (those which typically results from any large-scale development) and special impact categories (those which result from the fact that radioactive materials will be handled). 3 tables

Electronic Repository of Russian Historical Statistics

NARCIS (Netherlands)

Tykhonov, Vyacheslav; Kessler, Gijs; Markevich, Andrei; de Vries, Jerry

2014-01-01

The Electronic Repository for Russian Historical Statistics brings together data extracted from various published and unpublished sources in one place. Its principal focus is Russian economic and social history of the last three centuries (18th-21st). The repository caters to the needs of the

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

The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.

Science.gov (United States)

Romano, Barbara; Fasolino, Ines; Pagano, Ester; Capasso, Raffaele; Pace, Simona; De Rosa, Giuseppe; Milic, Natasa; Orlando, Pierangelo; Izzo, Angelo A; Borrelli, Francesca

2014-03-01

Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer. Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane. Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decompression of magma into repository tunnels

NARCIS (Netherlands)

Bokhove, Onno; Woods, A.W.

2002-01-01

It is nontrivial to find and design safe repository sites for nuclear waste. It appears common sense to drill tunnels as repository sites in a mountain in remote and relatively dry regions. However, erosion of the waste canisters by naturally abundant chemicals in the mountains water cycle remains a

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

Directory of Open Access Journals (Sweden)

Anika Eva Wagner

2013-01-01

Full Text Available A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways.

Paper and digital repositories in the United States

Directory of Open Access Journals (Sweden)

David F. Kohl

2003-09-01

Full Text Available What you've asked me to talk about today is basically what can libraries do with all the stuff they have and continue to get. Where do we put it all; what do we do with it? As we know, libraries have three core functions: collecting, organizing and preserving the key documents of the human enterprise. And, with apologies to Saint Paul, the greatest of these is preservation. For without preservation neither of the first two ultimately matter. My assignment this morning is to bring you up to date on one specific aspect of the preservation function, library repositories, and indeed, library repository developments in the US. The plan for this morning's presentation is the following: after a brief background review to give us a context for American developments we will examine first the various kinds of print repositories and then the various initiatives for electronic repositories. Because other presentations at this conference deal with electronic repositories, the main focus today will be on U.S. print repositories.

Institutional Repository Sebagai Sarana Komunikasi Ilmiah Yang Sustainable Dan Reliable

Directory of Open Access Journals (Sweden)

Faizuddin Harliansyah

2016-07-01

Full Text Available Abstract; Institutional repositories development has drawn the attention of many scholars throughout the world. Using the keywords ‘institutional repositories’, there are over 300 peer-reviewed articles related on the topic has been indexed in Library, Information Science, & Technology Abstracts (LISTA and SCOPUS. There are also hundreds of theses, dissertations, and websites dedicated on this blooming trends. These are proofs that the importance of IR in higher education has been acknowledged by many professionals in the field. This paper aims at clarifying the role of repositories in strengthening scholarly communication in higher education and research institution and explaining some basic repositories concepts (types of repositories and their characteristics, as well as exploring its relations with open access movement, the development ideas, and resources that could be kept in repositories and deposit policies. Abstrak; Pengembangan institutional repositories telah banyak menyita perhatian dari kalangan ilmiah di seluruh dunia. Melalui kata kunci ‘institutional repositories’, ada lebih dari 300 artikel terulas mitra bestari yang berhubungan dengan topik ini, yang telah terindeks di Library, Information Science, & Technology Abstracts (LISTA, dan SCOPUS. Terdapat juga ratusan tesis, disertasi, dan website yang mengulas trend ini. Inilah bukti bahwa pentingnya institutional repositories (IR telah dipahami oleh para profesional di bidangnya. Tulisan ini akan menjelaskan aturan-aturan repository dalam memperkuat komunikasi ilmiah di perguruan tinggi dan lembaga riset, menjelaskan konsep-konsep dasar repositories, termasuk tipe-tipe repository dan karakteristiknya. Tulisan ini juga akan memperdalam konsep repositories dalam hubungannya dengan gerakan open access, pengembangan ide-ide, sumber-sumber ilmiah yang dapat disimpan di repositories, serta kebijakan penyimpanan di dalamnya.

Environmental issues of repository licensing: an evaluation of a hypothetical high-level radioactive waste repository

International Nuclear Information System (INIS)

Owen, J.L.; McGinnis, J.T.; Harper, C.M.; Battelle Columbus Labs., OH)

1982-01-01

This paper presents results of an environmental assessment conducted under the direction of the Office of Nuclear Waste Isolation as part of the National Waste Terminal Storage program. The study defined a range of potential environmental effects of constructing, operating, decommissioning, and long-term isolation of a nuclear waste repository. The analytical methodology used to determine potential environmental effects required definition of a hypothetical environmental setting and repository. Potentially applicable regulatory requirements were identified and were used as guidelines to evaluate permitting feasibility. The environmental effects of repository development were analyzed for the two major time periods of concern: short term (the period of construction, operation, and decommissioning) and long term (the isolation period after decommissioning). As a result of this analysis, major environmental uncertainties and issues were identified. 11 references, 5 figures

Durable concrete for a waste repository - Measurement of ionic ingress

International Nuclear Information System (INIS)

Feldman, R.F.; Beaudoin, J.J.; Philipose, K.E.

1990-01-01

A waste repository for the below ground disposal of low level radioactive waste is planned at Chalk River Nuclear Laboratories. It relies greatly on the durability of concrete for the required 500 year service life. A research program to design durable concrete and predict its service life is in progress. The degradation of the concrete depends to a large extent on the rate of ingress of corrosive agents. Penetration of chloride and sulfate ions are particularly relevant. Twenty mix formulations were developed to create various types and qualities of concrete, and to study their behavior in different site environmental conditions. A total of 1,000 concrete specimens are being exposed at 20C and 45C to 25 different combinations of the corrosive agents including CO 2 . Procedures to measure the ionic profiles and to determine the factors controlling diffusion of the ions in the various concretes have been developed. Results of selected concrete systems exposed to chloride and sulfate solutions for 1 year are presented and discussed in terms of pore structure and permeability parameters of the concrete

Chemopreventive effects of in vitro digested and fermented bread in human colon cells.

Science.gov (United States)

Schlörmann, Wiebke; Hiller, Beate; Jahns, Franziska; Zöger, Romy; Hennemeier, Isabell; Wilhelm, Anne; Lindhauer, Meinolf G; Glei, Michael

2012-10-01

Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation. Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities. The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed. This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.

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.

New Roles, New Responsibilities: Examining Training Needs of Repository Staff

Directory of Open Access Journals (Sweden)

Natasha Simons

2012-05-01

Full Text Available INTRODUCTION Institutional repositories play a critical role in the research lifecycle. Funding agencies are increasingly seeking an improved return on their investment in research. Repositories facilitate this process by providing storage of, and access to, institutional research outputs and, more recently, research data. While repositories are generally managed within the academic library, repository staff require different skills and knowledge compared with traditional library roles. This study reports on a survey of Australasian institutional repository staff to identify skills and knowledge sets. METHODS Institutional repository staff working at universities in Australia and New Zealand were invited to participate in an online survey which incorporated both open and closed-ended question types. RESULTS The survey found significant gaps in the current provision of formal training and coursework related to institutional repositories, which echoed findings in the United Kingdom, Italy, and the United States. DISCUSSION There is clearly a need for more and varied training opportunities for repository professionals. Repository work requires a specific set of skills that can be difficult to find and institutions will benefit from investing in training and ongoing development opportunities for repository staff. CONCLUSION The data from this study could be used to facilitate staff recruitment, development, training, and retention strategies.

Evaluation of repository safety

Energy Technology Data Exchange (ETDEWEB)

Sagar, B.; Patrick, W.; Dasgupta, B.; Mohanty, S. [Center for Nuclear Waste Regulatory Analyses, San Antonio (United States)

2002-07-01

The United States high-level waste program requires evaluation of radiological safety during two distinct time intervals. The first interval, commonly referred to as the preclosure period, deals with receipt of waste at the site, transfer into disposal containers, if needed, emplacement in the underground openings, monitoring and maintenance activities, backfill and closure of the underground openings, and decontamination and decommissioning of the surface facilities of the geologic repository. The preclosure period may extend from a few tens of years to as long as a few hundred of years, depending on repository design and societal norms regarding a final decision to permanently seal the repository. During the preclosure or operational period, performance confirmation studies are conducted to provide a basis for updating and reevaluating estimates of postclosure performance and, finally, to provide a basis for a closure decision. The postclosure period during which expected repository performance must meet certain standards may range from ten thousands years, as it does in the United States, to millions of years, as it does in some European nations. Waste handling operations in the preclosure period are to be evaluated in relation to their potential effect on workers, members of general public, and the general environment. During this period, releases of radioactivity are to be monitored and appropriate actions taken whenever established limits are approached or exceeded. Preclosure safety is highly dependent on facility design, operational hardware and automated systems, operational sequences, and reliability of humans involved in operations. Preclosure safety analyses conducted before operations begin play a major role in the design process, selection of equipment, and development of operational procedures. Because of the complexity, duration, and spatial scales of the operations, analyses are conducted using mathematical models implemented in computer codes

Evaluation of repository safety

International Nuclear Information System (INIS)

Sagar, B.; Patrick, W.; Dasgupta, B.; Mohanty, S.

2002-01-01

The United States high-level waste program requires evaluation of radiological safety during two distinct time intervals. The first interval, commonly referred to as the preclosure period, deals with receipt of waste at the site, transfer into disposal containers, if needed, emplacement in the underground openings, monitoring and maintenance activities, backfill and closure of the underground openings, and decontamination and decommissioning of the surface facilities of the geologic repository. The preclosure period may extend from a few tens of years to as long as a few hundred of years, depending on repository design and societal norms regarding a final decision to permanently seal the repository. During the preclosure or operational period, performance confirmation studies are conducted to provide a basis for updating and reevaluating estimates of postclosure performance and, finally, to provide a basis for a closure decision. The postclosure period during which expected repository performance must meet certain standards may range from ten thousands years, as it does in the United States, to millions of years, as it does in some European nations. Waste handling operations in the preclosure period are to be evaluated in relation to their potential effect on workers, members of general public, and the general environment. During this period, releases of radioactivity are to be monitored and appropriate actions taken whenever established limits are approached or exceeded. Preclosure safety is highly dependent on facility design, operational hardware and automated systems, operational sequences, and reliability of humans involved in operations. Preclosure safety analyses conducted before operations begin play a major role in the design process, selection of equipment, and development of operational procedures. Because of the complexity, duration, and spatial scales of the operations, analyses are conducted using mathematical models implemented in computer codes

Semantic Linking of Learning Object Repositories to DBpedia

Science.gov (United States)

Lama, Manuel; Vidal, Juan C.; Otero-Garcia, Estefania; Bugarin, Alberto; Barro, Senen

2012-01-01

Large-sized repositories of learning objects (LOs) are difficult to create and also to maintain. In this paper we propose a way to reduce this drawback by improving the classification mechanisms of the LO repositories. Specifically, we present a solution to automate the LO classification of the Universia repository, a collection of more than 15…

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Directory of Open Access Journals (Sweden)

Peng Liu

2018-05-01

Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

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...

Intrinsic mitochondrial membrane potential change and associated events mediate apoptosis in chemopreventive effect of diclofenac in colon cancer.

Science.gov (United States)

Kaur, Jasmeet; Sanyal, S N

2010-01-01

The present study explored the role of intrinsic mitochondrial membrane potential (delta psi M) in NSAID-induced apoptosis in the early stages of colon cancer. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used to induce colon cancer and its chemoprevention was studied by diclofenac in a rat model. After 6 weeks of treatment with DMH (early stage), morphological analysis revealed a marked occurrence of preneoplastic features [i.e., mucosal plaque lesions (MPLs) in the colonic tissue]. Coadministration of diclofenac with DMH resulted in a significant reduction of these lesions, thereby proving the chemopreventive efficacy of diclofenac at the chosen anti-inflammatory dose. DMH treatment also led to a significant increase in delta psi M in the isolated colonocytes as assessed by JC-1 fluorescent staining, measured both by fluorescence microscopy and spectrofluorometerically. Further, there was seen a reduction in the number of cells showing low delta psi M, and hence monomer intensity of JC-1 by DMH treatment. To study the mechanism of these alterations in delta psi M in the present work, we studied the protein expression of important proapoptotic proteins, cytochrome c and Bax, by Western blot analysis and immunohistochemistry. DMH treatment reduced the mitochondrial translocation of Bax whereas cytochrome c was found to be located prominently in the mitochondria. Protein expression of antiapoptotic Bcl-2 was also studied in the colonic mucosa, which was expectedly found to be overexpressed after DMH treatment. Diclofenac treatment ameliorated the elevated delta psi M and its associated events to exert its chemopreventive action against early stages of colon cancer.

Researching radioactive waste disposal. [Underground repository

Energy Technology Data Exchange (ETDEWEB)

Feates, F; Keen, N [UKAEA Research Group, Harwell. Atomic Energy Research Establishment

1976-02-16

At present it is planned to use the vitrification process to convert highly radioactive liquid wastes, arising from nuclear power programme, into glass which will be contained in steel cylinders for storage. The UKAEA in collaboration with other European countries is currently assessing the relative suitability of various natural geological structures as final repositories for the vitrified material. The Institute of Geological Sciences has been commissioned to specify the geological criteria that should be met by a rock structure if it is to be used for the construction of a repository though at this stage disposal sites are not being sought. The current research programme aims to obtain basic geological data about the structure of the rocks well below the surface and is expected to continue for at least three years. The results in all the European countries will then be considered so that the United Kingdom can choose a preferred method for isolating their wastes. It is only at that stage that a firm commitment may be made to select a site for a potential repository, when a far more detailed scientific research study will be instituted. Heat transfer problems and chemical effects which may occur within and around repositories are being investigated and a conceptual design study for an underground repository is being prepared.

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...... for systematically analysing institutions technical and organisational requirements for a remote bit repository. Instead of viewing a bit repository simply as Archival Storage for the institutions repositories, we argue for viewing it as consisting of a subset of functions from all entities defined by the OAIS...... Reference Model. The work is motivated by and used in a current Danish feasibility study for establishing a national bit repository. The study revealed that depending on their missions and the collections they hold, the institutions have varying requirements e.g. for bit safety, accessibility...

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...... for systematically analysing the technical and organizational requirements of institutions for a remote bit repository. Instead of viewing a bit repository simply as Archival Storage for the institutions’ repositories, we argue for viewing it as consisting of a subset of functions from all entities defined...... by the OAIS Reference Model. The work is motivated by and used in a current Danish feasibility study for establishing a national bit repository. The study revealed that depending on their missions and the collections they hold, the institutions have varying requirements, such as for bit safety, accessibility...

Tools for Managing Repository Objects

OpenAIRE

Banker, Rajiv D.; Isakowitz, Tomas; Kauffman, Robert J.; Kumar, Rachna; Zweig, Dani

1993-01-01

working Paper Series: STERN IS-93-46 The past few years have seen the introduction of repository-based computer aided software engineering (CASE) tools which may finally enable us to develop software which is reliable and affordable. With the new tools come new challenges for management: Repository-based CASE changes software development to such an extent that traditional approaches to estimation, performance, and productivity assessment may no longer suffice - if they ever...

Repository seal materials performance for a SALT Repository Project 5-year code/model development plan: Draft

International Nuclear Information System (INIS)

1987-06-01

This document describes an integrated laboratory testing and model development effort for the seal system for a high-level nuclear waste repository in salt. The testing and modeling efforts are designed to determine seal material response in the repository environment, to provide models of seal system components for performance assessment, and to assist in the development of seal system designs. A code/model development and performance analysis program will be performed to predict the short- and long-term response of seal materials and seal components. The results from these analyses will be used to support the material testing activities on this contract and to support performance assessment activities that are conducted in other parts of the Salt Repository Project (SRP). 48 refs., 15 figs., 4 tabs

Gas generation and release from the VLJ repository

International Nuclear Information System (INIS)

Vieno, T.; Valkiainen, M.

1992-01-01

The VLJ repository is an underground disposal facility located at the Olkiluoto nuclear power plant site on the west coast of Finland. The repository will house low (LLW) and intermediate level radioactive wastes (MLW) from the TVO I and TVO II BWR's and the spent fuel interim store at Olkiluoto. The disposal rooms have been excavated at a depth of 60... 100 meters in the crystalline bedrock. They consist of two rock silos - one for the LLW and the other for MLW. Low level waste is usually packed in steel drums and steel boxes. Medium level wastes consists of bituminized resins in steel drums. Wastes packages are emplaced in concrete boxes before transportation into the repository. Low level wastes are emplaced in the shotcreted rock silo where no backfilling will used. For medium level wastes, a separate silo of reinforced concrete has been constructed inside the rock silo. No backfilling will be used inside the concrete silo and an opening will be made in the lid of the concrete silo for gas release. The microbial degradation of low level wastes is the principle gas generation process in the repository. The gas transport though the bedrock covering the repository is evaluated with the help of ground water flow study. It is recommended that the shotcrete lining on the ceiling of the repository cavern is partly removed before the final sealing of the repository. Provided that dissipation of gases from the disposal cavern into the rock can been assured, the overall effects of gas generation on the long-term safety of the repository are insignificant. 10 refs., 6 figs

Post-closure radiation dose assessment for Yucca Mountain repository

International Nuclear Information System (INIS)

Jia Mingyan; Zhang Xiabin; Yang Chuncai

2006-01-01

A brief introduction of post-closure long-term radiation safety assessment results was represented for the yucca mountain high-level waste geographic disposal repository. In 1 million years after repository closure, for the higher temperature repository operating mode, the peak annual dose would be 150 millirem (120 millirem under the lower-temperature operating mode) to a reasonably maximally exposed individual approximately 18 kilometers (11 miles) from the repository. The analysis of a drilling intrusion event occurring at 30,000 years indicated a peak of the mean annual dose to the reasonably maximally exposed individual approximately 18 kilometers (11 miles) downstream of the repository would be 0.002 millirem. The analysis of an igneous activity scenario, including a volcanic eruption event and igneous intrusion event indicated a peak of the mean annual dose to the reasonably maximally exposed individual approximately 18 kilometers downstream of the repository would be 0.1 millirem. (authors)

Design of repository sealing systems - 1981

International Nuclear Information System (INIS)

Ellison, R.D.; Shukla, D.K.; Kelsall, P.C.; D'Appolonia Consulting Engineers, Albuquerque, NM)

1982-01-01

Isolating nuclear waste in geologic repositories will require the sealing of penetrations such as access shafts and tunnels, disposal rooms, and exploration boreholes. This paper discusses seal designs developed for a repository in bedded salt referenced to the stratigraphy of southeastern New Mexico. Designs are based on a multiple component concept whereby individual components are designed for a specific function and location. For a repository in salt the major function of the seals is to exclude groundwater inflow. Two main types of component are included for this purpose: (1) bulk-heads are dense concrete structures keyed into the walls of the penetration and are intended to reduce flow at the interface between the seal and the salt; (2) backfills are granular materials compacted in place in the penetration. In the repository the major backfill material is crushed salt, which is expected to consolidate and recrystallize as the rooms close in response to salt creep. Densely compacted clays will be used as backfill in the shafts closer to potential sources of water inflow. 22 references, 10 figures, 1 table

Creation of Data Repositories to Advance Nursing Science.

Science.gov (United States)

Perazzo, Joseph; Rodriguez, Margaret; Currie, Jackson; Salata, Robert; Webel, Allison R

2017-12-01

Data repositories are a strategy in line with precision medicine and big data initiatives, and are an efficient way to maximize data utility and form collaborative research relationships. Nurse researchers are uniquely positioned to make a valuable contribution using this strategy. The purpose of this article is to present a review of the benefits and challenges associated with developing data repositories, and to describe the process we used to develop and maintain a data repository in HIV research. Systematic planning, data collection, synthesis, and data sharing have enabled us to conduct robust cross-sectional and longitudinal analyses with more than 200 people living with HIV. Our repository building has also led to collaboration and training, both in and out of our organization. We present a pragmatic and affordable way that nurse scientists can build and maintain a data repository, helping us continue to make to our understanding of health phenomena.

Reducing Psychological Resistance to Digital Repositories

Directory of Open Access Journals (Sweden)

Brian Quinn

2010-06-01

Full Text Available The potential value of digital repositories is dependent on the cooperation of scholars to deposit their work. Although many researchers have been resistant to submitting their work, the literature on digital repositories contains very little research on the psychology of resistance. This article looks at the psychological literature on resistance and explores what its implications might be for reducing the resistance of scholars to submitting their work to digital repositories. Psychologists have devised many potentially useful strategies for reducing resistance that might be used to address the problem; this article examines these strategies and how they might be applied.

Augmenting interoperability across repositories architectural ideas

CERN Multimedia

CERN. Geneva

2005-01-01

The aDORe digital repository architecture designed and implemented by the Los Alamos Research Library is fully standards-based and highly modular, with the various components of the architecture interacting in a protocol-driven manner. Although aDORe was designed for use in the context of the Los Alamos Library, its modular and standards-based design has led to interesting insights regarding possible new levels of interoperability in a federation of heterogeneous repositories. The presentation will discuss these insights, and will illustrate that attractive federations of repositories can be built by introducing rather basic interoperability requirements. The presentation will also show that, once these requirements are met, a powerful service framework that overlays the federation can emerge.

Executive-style briefings on selected repository design issues

International Nuclear Information System (INIS)

1978-01-01

This document is a collection of executive-style briefings on selected repository design issues. Most of the briefings discuss differences between the US repository design bases presented in US Working Draft on Repository Physical Descriptions in a Salt Formation, prepared in support of INFCE discussions of May 1978 and the FRG-Netherlands design bases, presented in Design Study of a Radioactive Waste Repository to be Mined in a Medium-Size Salt Dome by Hamstra and Velzeboer, Netherlands Energy Research Foundation, January 1978. Advantages and disadvantages of the two sets of design bases are discussed, and the impacts of adopting either of these bases on the other's programs and positions are identified

Repository-analog experiments of nuclear waste leaching and migration

International Nuclear Information System (INIS)

Seitz, M.G.

1982-01-01

The potential for radionuclide migration from a breached nuclear-waste repository depends on the leaching and subsequent interaction of the leached radionuclides with materials in the groundwater flow path. An attempt is made to consider all interactions using experiments that integrate repository materials. Results of a repository-analog experiment using borosilicate glass, fissured granite, and flowing water suggest: (1) plutonium was immobile possibly because of its low solubility; (2) caesium migrated down slowly because of sorption; and (3) neptunium remained oxidized even in water of low oxidation potential. By summing the effects of all interactions, not just sorption, the repository-analog experiment produced radionuclide migration that could be expected from a breached repository. (author)

Publishers and repositories

CERN Multimedia

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

Business models for digital repositories

CERN Document Server

CERN. Geneva; Bjørnshauge, Lars

2007-01-01

Those setting up, or planning to set up, a digital repository may be interested to know more about what has gone before them. What is involved, what is the cost, how many people are needed, how have others made the case to their institution, and how do you get anything into it once it is built? I have recently undertaken a study of European repository business models for the DRIVER project and will present an overview of the findings.

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.

Waste package/repository impact study: Final report

International Nuclear Information System (INIS)

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

Repository exploration

International Nuclear Information System (INIS)

Pentz, D.L.

1984-01-01

This paper discusses exploration objectives and requirements for a nuclear repository in the U.S.A. The importance of designing the exploration program to meet the system performance objectives is emphasized and some examples of the extent of exploration required before the License Application for Construction Authorization is granted are also discussed

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...

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.

Gabbro as a host rock for a nuclear waste repository

International Nuclear Information System (INIS)

Ahlbom, K.; Leijon, B.; Smellie, J.; Liedholm, M.

1992-09-01

As an alternative to granitic rocks, gabbro and other basic rock types have been investigated with respect to their suitability to host a nuclear waste repository. The present report summarizes and examines existing geoscientific knowledge of relevance in assessing the potential merits of gabbro as a repository host rock. Implications in terms of site selection, repository construction and post-closure repository performance are also discussed. The objective of the study is to provide a basis for decisions as regards future consideration of the gabbro alternative. It is found that there are rather few gabbro bodies in Sweden, that are potentially of sufficient size to host a repository. Thus, gabbro offers little latitude as regards site selection. In comparison to siting a repository in granitic rocks, this is a major disadvantage, and it may in fact remove gabbro from further consideration. The potential advantages of gabbro refer to repository performance, and include low hydraulic conductivity and a chemical environment promoting efficient radionuclide retardation. However, results from field investigations show that groundwater flow in gabbro bodies is largely controlled by intersecting heterogeneities, in particular granitic dykes, that are significantly more conductive to water than the gabbro. In the far-field scale significant to repository performance, this may reduce or eliminate the potential effects of favourable hydraulic and chemical characteristics of the gabbro itself. In conclusion, there are apparent difficulties associated with siting a repository in gabbro, due to lack of sufficiently large gabbro bodies. On the basis of the present state of knowledge, no decisive differences can be demonstrated when comparing gabbro with granitic rocks, neither with respects to repository construction, nor as regards repository performance. (au)

Design and production of the KBS-3 repository

International Nuclear Information System (INIS)

Moren, Lena

2010-12-01

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

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 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... connection with any geologic repository developed under Subtitle A of Title I, or under Title IV, of the...

Characterisation of discharge areas of radionuclides originating from nuclear waste repositories

International Nuclear Information System (INIS)

Marklund, L.; Woerman, A.

2008-01-01

In this study, we investigate if there are certain landscape elements that will generally act as discharge areas for radio-nuclides leaking from a subsurface deposit of nuclear waste. We also characterize the typical properties that distinguish these areas from others. Understanding the processes controlling the clustering of discharge to certain areas is an additional topic of study. Landscape topography is the most important driving force for groundwater flow. Because groundwater is the main transporting agent for migrating radio-nuclides, the topography will determine the flow paths of leaking radionuclides. How topography and heterogeneities in the subsurface affect the discharge distribution of the radionuclides is the main scope of this study. An analytical and a numerical model are used. Conclusions are: Our results suggest that the varieties of landscape elements which have potential for receiving significant amounts of radio-nuclides are limited. To save recourses, the surficial radiological assessments should therefore be focused in these areas. Furthermore, the discharge areas of groundwater from repository depth have defining characteristics that distinguish them from discharge areas of shallower groundwater flow cells. Due to the similarities within deep groundwater discharge areas, one can make site-specific analyses of those areas, which have a broad applicability for migration of radio-nuclides originating from a nuclear waste repository (author)(tk)

Conceptual design of repository facilities

International Nuclear Information System (INIS)

Beale, H.; Engelmann, H.J.; Souquet, G.; Mayence, M.; Hamstra, J.

1980-01-01

As part of the European Economic Communities programme of research into underground disposal of radioactive wastes repository design studies have been carried out for application in salt deposits, argillaceous formations and crystalline rocks. In this paper the design aspects of repositories are reviewed and conceptual designs are presented in relation to the geological formations under consideration. Emphasis has been placed on the disposal of vitrified high level radioactive wastes although consideration has been given to other categories of radioactive waste

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...

Ventilation System Strategy for a Prospective Korean Radioactive Waste Repository

International Nuclear Information System (INIS)

Kim, Jin; Kwon, Sang Ki

2005-01-01

In the stage of conceptual design for the construction and operation of the geologic repository for radioactive wastes, it is important to consider a repository ventilation system which serves the repository working environment, hygiene and safety of the public at large, and will allow safe maintenance like moisture content elimination in repository for the duration of the repositories life, construction/operation/closure, also allowing safe waste transportation and emplacement. This paper describes the possible ventilation system design criteria and requirements for the prospective Korean radioactive waste repositories with emphasis on the underground rock cavity disposal method in the both cases of low and medium-level and high-level wastes. It was found that the most important concept is separate ventilation systems for the construction (development) and waste emplacement (storage) activities. In addition, ventilation network system modeling, natural ventilation, ventilation monitoring systems and real time ventilation simulation, and fire simulation and emergency system in the repository are briefly discussed.

Types of safety assessments of near surface repository for radioactive waste

International Nuclear Information System (INIS)

Mateeva, M.

2004-01-01

The purpose of this article is to presents the classification of different types safety assessments of near surface repository for low and intermediate level radioactive waste substantiated with results of safety assessments generated in Bulgaria. The different approach of safety assessments applied for old existing repository as well as for site selection for construction new repository is outlined. The regulatory requirements in Bulgaria define three main types of assessments: Safety assessment; Technical substation of repository safety; Assessment of repository influence on environment that is in form of report prepared from the Ministry of environment and waters on the base of results obtained in two first types of assessments. Additionally first type is subdivided in three categories - preliminary safety assessment, safety assessment and post closure safety assessment, which are generated using deterministic approach. The technical substation of repository safety is generated using probabilistic approach. Safety assessment results that are presented here are based on evaluation of existing old repository type 'Radon' in Novi Han and real site selection procedure for new near surface repository for low and intermediate level radioactive waste from nuclear power station in Kozloduy. The important role of safety assessment for improvement the repository safety as well as for repository licensing, correct site selection and right choice of engineer barriers and repository design is discussed using generated results. (author)

Data Stewardship: Environmental Data Curation and a Web-of-Repositories

Directory of Open Access Journals (Sweden)

Karen S. Baker

2009-10-01

Full Text Available Scientific researchers today frequently package measurements and associated metadata as digital datasets in anticipation of storage in data repositories. Through the lens of environmental data stewardship, we consider the data repository as an organizational element central to data curation. One aspect of non-commercial repositories, their distance-from-origin of the data, is explored in terms of near and remote categories. Three idealized repository types are distinguished – local, center, and archive - paralleling research, resource, and reference collection categories respectively. Repository type characteristics such as scope, structure, and goals are discussed. Repository similarities in terms of roles, activities and responsibilities are also examined. Data stewardship is related to care of research data and responsible scientific communication supported by an infrastructure that coordinates curation activities; data curation is defined as a set of repeated and repeatable activities focusing on tending data and creating data products within a particular arena. The concept of “sphere-of-context” is introduced as an aid to distinguishing repository types. Conceptualizing a “web-of-repositories” accommodates a variety of repository types and represents an ecologically inclusive approach to data curation.

Harvesting NASA's Common Metadata Repository

Science.gov (United States)

Shum, D.; Mitchell, A. E.; Durbin, C.; Norton, J.

2017-12-01

As part of NASA's Earth Observing System Data and Information System (EOSDIS), the Common Metadata Repository (CMR) stores metadata for over 30,000 datasets from both NASA and international providers along with over 300M granules. This metadata enables sub-second discovery and facilitates data access. While the CMR offers a robust temporal, spatial and keyword search functionality to the general public and international community, it is sometimes more desirable for international partners to harvest the CMR metadata and merge the CMR metadata into a partner's existing metadata repository. This poster will focus on best practices to follow when harvesting CMR metadata to ensure that any changes made to the CMR can also be updated in a partner's own repository. Additionally, since each partner has distinct metadata formats they are able to consume, the best practices will also include guidance on retrieving the metadata in the desired metadata format using CMR's Unified Metadata Model translation software.

Core Certification of Data Repositories: Trustworthiness and Long-Term Stewardship

Science.gov (United States)

de Sherbinin, A. M.; Mokrane, M.; Hugo, W.; Sorvari, S.; Harrison, S.

2017-12-01

Scientific integrity and norms dictate that data created and used by scientists should be managed, curated, and archived in trustworthy data repositories thus ensuring that science is verifiable and reproducible while preserving the initial investment in collecting data. Research stakeholders including researchers, science funders, librarians, and publishers must also be able to establish the trustworthiness of data repositories they use to confirm that the data they submit and use remain useful and meaningful in the long term. Data repositories are increasingly recognized as a key element of the global research infrastructure and the importance of establishing their trustworthiness is recognised as a prerequisite for efficient scientific research and data sharing. The Core Trustworthy Data Repository Requirements are a set of universal requirements for certification of data repositories at the core level (see: https://goo.gl/PYsygW). They were developed by the ICSU World Data System (WDS: www.icsu-wds.org) and the Data Seal of Approval (DSA: www.datasealofapproval.org)—the two authoritative organizations responsible for the development and implementation of this standard to be further developed under the CoreTrustSeal branding . CoreTrustSeal certification of data repositories involves a minimally intensive process whereby repositories supply evidence that they are sustainable and trustworthy. Repositories conduct a self-assessment which is then reviewed by community peers. Based on this review CoreTrustSeal certification is granted by the CoreTrustSeal Standards and Certification Board. Certification helps data communities—producers, repositories, and consumers—to improve the quality and transparency of their processes, and to increase awareness of and compliance with established standards. This presentation will introduce the CoreTrustSeal certification requirements for repositories and offer an opportunity to discuss ways to improve the contribution of

United States Crystalline Repository Project - key research areas

International Nuclear Information System (INIS)

Patera, E.S.

1986-01-01

The Crystalline Repository Project is responsible for siting the second high-level nuclear waste repository in crystalline rock for the US Department of Energy. A methodology is being developed to define data and information needs and a way to evaluate that information. The areas of research the Crystalline Repository Project is involved in include fluid flow in a fractured network, coupled thermal, chemical and flow processes and cooperation in other nations and OECD research programs

Towards Content Development For Institutional Digital Repository ...

African Journals Online (AJOL)

The growth in Information and Communication Technology has lead to the emergence of Institutional Digital Repository, a digital archive for the preservation and dissemination of institutional research outputs. Institutional Digital Repositories make possible global dissemination of research outputs through the use of the ...

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

Groundwater flow modelling of an abandoned partially open repository

International Nuclear Information System (INIS)

Bockgaard, Niclas

2010-12-01

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

Current Status of Deep Geological Repository Development

International Nuclear Information System (INIS)

Budnitz, R J

2005-01-01

This talk provided an overview of the current status of deep-geological-repository development worldwide. Its principal observation is that a broad consensus exists internationally that deep-geological disposal is the only long-term solution for disposition of highly radioactive nuclear waste. Also, it is now clear that the institutional and political aspects are as important as the technical aspects in achieving overall progress. Different nations have taken different approaches to overall management of their highly radioactive wastes. Some have begun active programs to develop a deep repository for permanent disposal: the most active such programs are in the United States, Sweden, and Finland. Other countries (including France and Russia) are still deciding on whether to proceed quickly to develop such a repository, while still others (including the UK, China, Japan) have affirmatively decided to delay repository development for a long time, typically for a generation of two. In recent years, a major conclusion has been reached around the world that there is very high confidence that deep repositories can be built, operated, and closed safely and can meet whatever safety requirements are imposed by the regulatory agencies. This confidence, which has emerged in the last few years, is based on extensive work around the world in understanding how repositories behave, including both the engineering aspects and the natural-setting aspects, and how they interact together. The construction of repositories is now understood to be technically feasible, and no major barriers have been identified that would stand in the way of a successful project. Another major conclusion around the world is that the overall cost of a deep repository is not as high as some had predicted or feared. While the actual cost will not be known in detail until the costs are incurred, the general consensus is that the total life-cycle cost will not exceed a few percent of the value of the

Dietary Glucosinolates Sulforaphane, Phenethyl Isothiocyanate, Indole-3-Carbinol/3,3'-Diindolylmethane: Anti-Oxidative Stress/Inflammation, Nrf2, Epigenetics/Epigenomics and In Vivo Cancer Chemopreventive Efficacy.

Science.gov (United States)

Fuentes, Francisco; Paredes-Gonzalez, Ximena; Kong, Ah-Ng Tony

2015-05-01

Glucosinolates are a group of sulfur-containing glycosides found in many plant species, including cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower. Accumulating evidence increasingly supports the beneficial effects of dietary glucosinolates on overall health, including as potential anti-cancer agents, because of their role in the prevention of the initiation of carcinogenesis via the induction of cellular defense detoxifying/antioxidant enzymes and their epigenetic mechanisms, including modification of the CpG methylation of cancer-related genes, histone modification regulation and changes in the expression of miRNAs. In this context, the defense mechanism mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against oxidative stress and reactive metabolites of carcinogens. In this review, we summarize the cancer chemopreventive role of naturally occurring glucosinolate derivatives as inhibitors of carcinogenesis, with particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo human cancer animal models.

Earthquakes - a danger to deep-lying repositories?

International Nuclear Information System (INIS)

2012-03-01

This booklet issued by the Swiss National Cooperative for the Disposal of Radioactive Waste NAGRA takes a look at geological factors concerning earthquakes and the safety of deep-lying repositories for nuclear waste. The geological processes involved in the occurrence of earthquakes are briefly looked at and the definitions for magnitude and intensity of earthquakes are discussed. Examples of damage caused by earthquakes are given. The earthquake situation in Switzerland is looked at and the effects of earthquakes on sub-surface structures and deep-lying repositories are discussed. Finally, the ideas proposed for deep-lying geological repositories for nuclear wastes are discussed

Stream-simulation experiments for waste-repository investigations

International Nuclear Information System (INIS)

Seitz, M.G.

1980-01-01

The potential for radionuclide migration by groundwater flow from a breached-water repository depends on the leaching process and on chemical changes that might occur as the radionuclide moves away from the repository. Therefore, migration involves the interactions of leached species with (1) the waste and canister, (2) the engineered barrier, and (3) the geologic materials surrounding the repository. Rather than attempt to synthesize each species and study it individually, another approach is to integrate all species and interactions using stream-simulation experiments. Interactions identified in these studies can then be investigated in detail in simpler experiments

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.

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment.

Science.gov (United States)

Puccinelli, Michael T; Stan, Silvia D

2017-07-28

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

The function of packing materials in a high-level nuclear waste repository and some candidate materials: Salt Repository Project

International Nuclear Information System (INIS)

Bunnell, L.R.; Shade, J.W.

1987-03-01

Packing materials should be included in waste package design for a high-level nuclear waste repository in salt. A packing material barrier would increase confidence in the waste package by alleviating possible shortcomings in the present design and prolonging confinement capabilities. Packing materials have been studied for uses in other geologic repositories; appropriately chosen, they would enhance the confinement capabilities of salt repository waste packages in several ways. Benefits of packing materials include retarding or chemically modifying brines to reduce corrosion of the waste package, providing good thermal conductivity between the waste package and host rock, retarding or absorbing radionuclides, and reducing the massiveness of the waste package. These benefits are available at low percentage of total repository cost, if the packing material is properly chosen and used. Several candidate materials are being considered, including oxides, hydroxides, silicates, cement-based mixtures, and clay mixtures. 18 refs

Representation of an open repository in groundwater flow models

International Nuclear Information System (INIS)

Painter, Scott; Sun, Alexander

2005-08-01

The effect of repository tunnels on groundwater flow has been identified as a potential issue for the nuclear waste repository being considered by SKB for a fractured granite formation in Sweden. In particular, the following pre-closure and post-closure processes have been identified as being important: inflows into open tunnels as functions of estimated grouting efficiencies, drawdown of the water table in the vicinity of the repository, upcoming of saline water, 'turnover' of surface water in the upper bedrock, and resaturation of backfilled tunnels following repository closure. The representation of repository tunnels within groundwater models is addressed in this report. The primary focus is on far-field flow that is modeled with a continuum porous medium approximation. Of particular interest are the consequences of the tunnel representation on the transient response of the groundwater system to repository operations and repository closure, as well as modeling issues such as how the water-table free surface and the coupling to near-surface hydrogeology should be handled. The overall objectives are to understand the consequences of current representations and to identify appropriate approximations for representing open tunnels in future groundwater modeling studies. The following conclusions can be drawn from the results of the simulations: 1. Two-phase flow may be induced in the vicinity of repository tunnels during repository pre-closure operations, but the formation of a two-phase flow region will not significantly affect far-field flow or inflows into tunnels. 2. The water table will be drawn down to the repository horizon and tunnel inflows will reach a steady-state value within about 5 years. 3. Steady-state inflows at the repository edge are estimated to be about 250 m 3 /year per meter of tunnel. Inflows will be greater during the transient de-watering period and less for tunnel locations closer to the repository center. 4. Significant amounts of water

Representation of an open repository in groundwater flow models

Energy Technology Data Exchange (ETDEWEB)

Painter, Scott; Sun, Alexander [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses

2005-08-01

The effect of repository tunnels on groundwater flow has been identified as a potential issue for the nuclear waste repository being considered by SKB for a fractured granite formation in Sweden. In particular, the following pre-closure and post-closure processes have been identified as being important: inflows into open tunnels as functions of estimated grouting efficiencies, drawdown of the water table in the vicinity of the repository, upcoming of saline water, 'turnover' of surface water in the upper bedrock, and resaturation of backfilled tunnels following repository closure. The representation of repository tunnels within groundwater models is addressed in this report. The primary focus is on far-field flow that is modeled with a continuum porous medium approximation. Of particular interest are the consequences of the tunnel representation on the transient response of the groundwater system to repository operations and repository closure, as well as modeling issues such as how the water-table free surface and the coupling to near-surface hydrogeology should be handled. The overall objectives are to understand the consequences of current representations and to identify appropriate approximations for representing open tunnels in future groundwater modeling studies. The following conclusions can be drawn from the results of the simulations: 1. Two-phase flow may be induced in the vicinity of repository tunnels during repository pre-closure operations, but the formation of a two-phase flow region will not significantly affect far-field flow or inflows into tunnels. 2. The water table will be drawn down to the repository horizon and tunnel inflows will reach a steady-state value within about 5 years. 3. Steady-state inflows at the repository edge are estimated to be about 250 m{sup 3}/year per meter of tunnel. Inflows will be greater during the transient de-watering period and less for tunnel locations closer to the repository center. 4. Significant

The industrial organization of the repository. Pitfall or logical?

International Nuclear Information System (INIS)

Frostenson, Magnus

2010-11-01

From a systems perspective the organization of the Swedish final repository project for nuclear waste is studied. Different aspects of organization are identified in the report, covering dimensions of geographical, operative, structural, responsibility and contextual organization. Following SKB's site selection for the applications for the final repository for spent nuclear system and the closing of the surplus value agreement, issues concerning operative, structural and contextual organization tend to become particularly pressing, which is reflected in three research questions: - How will the final repository project be organized operatively and structurally over time? - Why is the final repository project organized in this way by SKB? - What kind of contextual organization takes place in the final repository project and what are the consequences of these activities? How the different industrial units of the final repository project should be run and within which structure, for example concerning ownership and integration of units, is established in the report. SKB's reasons for choosing this kind of organization are also highlighted. Apart from legal and safety-related demands that must be met together with the demands of the owners, SKB's strategic preference for insourcing conditions organizational choices. The traditional task centred operative and structural organization of SKB is also reflected in the organizational choices for the present and future units of the final depository system. Contextual organization implies deepened actor relationships between SKB's owners and SKB on the one side and the municipalities Oesthammar and Oskarshamn on the other. Through active organizing, the final repository arena 'narrows down' and the final repository issue turns into an in many respects local issue. There is a clear tendency that the roles of SKB are multiplied in order to handle the demands that central stakeholders - in particular the municipalities - place on

Transfer systems in an underground repository

International Nuclear Information System (INIS)

Berg, H.P.; Ehrlich, D.

1991-01-01

In addition to logistic problem definitions taking into account the waste types of the wastes to be disposed of and the mining conditions, transport and handling of radioactive wastes in a repository, particularly require the keeping of safety technological marginal conditions mainly resulting from the accident analyses carried out. The realization of these safety technological aspects is described taking the planned Konrad repository as an example. (author)

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,…

Classifying decommissioning wastes for allocation to appropriate final repositories

International Nuclear Information System (INIS)

Alder, J.C.; Tunaboylu, K.

1982-01-01

For the safe disposal of radioactive wastes in different repositories, it is of advantage to classify them in well-defined conditioned categories, appropriate for final disposal. These categories, the so-called waste sorts are characterized by similar radionuclide distribution, similar nuclide-specific activity concentrations and similar waste matrix. A methodology is presented for classifying decommissioning wastes and is applied to the decommissioning wastes arising from a Swiss program of 6 GWe. The amounts and nuclide-specific activity inventories of the decommissioning waste sorts have been estimated. A first allocation into two different repository types has been performed. Such a classification enables one to define the source parameters for repository safety analysis and allows one to allocate the different waste categories into appropriate final repositories. This work presents a first iteration to determine which waste sorts belong to which repository type. The characteristics of waste sorts have to be better defined and the protective strength of the repository barriers has to be optimized. 7 references, 2 figures, 4 tables

Shaft placement in a bedded salt repository

International Nuclear Information System (INIS)

Klasi, M.L.

1982-10-01

Preferred shaft pillar sizes and shaft locations were determined with respect to the induced thermal stresses in a generic bedded salt repository at a depth of 610 m with a gross thermal loading of 14.8 W/m 2 . The model assumes isotropic material properties, plane strain and linear elastic behavior. Various shaft locations were analyzed over a 25 year period. The thermal results show that for this time span, the stratigraphy is unimportant except for the region immediately adjacent to the repository. The thermomechanical results show that for the given repository depth of 610 m, a minimum central shaft pillar radius of 244 m is required to equal the material strength in the barrier pillar. An assumed constant stress and constant temperature distribution creep model of the central shaft region adjacent to the repository conservatively overestimates a creep closure of 310 mm in a 6.1 m diameter centrally-located shaft

Safety analysis of the VLJ repository

International Nuclear Information System (INIS)

Vieno, T.; Nordman, H.

1991-05-01

The VLJ repository is an underground disposal facility for the low and medium level waste generated at the Olkiluoto nuclear power plant. The repository is located within 1 km from TVO I and TVO II (2 x 710 MWe) BWR's on the Olkiluoto island at the west coast of Finland. It contains two rock silos excavated at the depth of 60...100 meters in the bedrock. Low level waste will be disposed of in a shotcreted rock silo. For bituminized medium level waste, a separate silo of reinforced concrete has been built inside the shotcreted rock silo. The post-closure safety analysis has been done for the Final Safety Analysis Report (FSAR) of the VLJ repository. In addition to the normal evolution scenario, several disturbed evolution and accident scenarios have been analysed. In the reference scenario, radio-nuclides are assumed to be released from the bituminized waste within 500 years, the concrete silo is assumed to gradually disintegrate and finally to collapse at 5 000 years, all concrete in the silo is assumed to be also chemically depleted within 6 000 years, and all the seals of the repository are assumed to deteriorate within 12 000 years. The ability of alone natural barriers to restrict the release of radionuclides into the biosphere has been evaluated by means of scenarios where the degradation of engineered barriers has been assumed to take place at a still faster rate. In one of the disturbed evolution scenarios it has been assumed that the concrete silo for medium level waste is severely impaired immediately after sealing of the repository. Effects of gas generation and consequences of human intrusion have been evaluated, too. The results of the safety analysis show that radiation doses of any significance are caused only if a well is bored in the vicinity of the repository or if the groundwater discharge spot is inhabited and used for cultivation. In the reference scenario the maximum expectation value of the individual dose rate is 0.3 mSv/a

Diversion path analysis for the Swedish geological repository

International Nuclear Information System (INIS)

Fritzell, Anni; Meer, Klaas Van Der

2008-02-01

The Swedish strategy to handle the spent fuel from the nuclear power plants is direct disposal in a geological repository. The safeguards regime covering all nuclear material in the state will be expanded to cover the new repository, which will require a novel safeguards approach due mainly to the inaccessibility of the fuel after disposal. The safeguards approach must be able to provide a high level of assurance that the fuel in the repository not diverted, but must also be resource efficient. An attractive approach with regards to use of resources is to monitor only the access points to the repository, i.e. the openings. The implementation of such an approach can only be allowed if it is shown to be sufficiently secure. With the purpose of determining the applicability of this 'black box' approach, a diversion path analysis for the Swedish geological repository has been carried out. The result from the analysis shows that all credible diversion paths could be covered by the black-box safeguards approach provided that the identified boundary conditions can be met

Diversion path analysis for the Swedish geological repository

Energy Technology Data Exchange (ETDEWEB)

Fritzell, Anni (Dept. of Physics and Astronomy, Uppsala Univ., Uppsala (Sweden)); Meer, Klaas Van Der (Belgian Nuclear Research Center SCK.CEN (BG))

2008-02-15

The Swedish strategy to handle the spent fuel from the nuclear power plants is direct disposal in a geological repository. The safeguards regime covering all nuclear material in the state will be expanded to cover the new repository, which will require a novel safeguards approach due mainly to the inaccessibility of the fuel after disposal. The safeguards approach must be able to provide a high level of assurance that the fuel in the repository not diverted, but must also be resource efficient. An attractive approach with regards to use of resources is to monitor only the access points to the repository, i.e. the openings. The implementation of such an approach can only be allowed if it is shown to be sufficiently secure. With the purpose of determining the applicability of this 'black box' approach, a diversion path analysis for the Swedish geological repository has been carried out. The result from the analysis shows that all credible diversion paths could be covered by the black-box safeguards approach provided that the identified boundary conditions can be met

Salt Repository Project shaft design guide: Revision 0

International Nuclear Information System (INIS)

1987-12-01

The Salt Repository Project (SRP) Shaft Design Guide (SDG) and the accompanying SRP Input to Seismic Design define the basic approach for developing appropriate shaft designs for a high-level nuclear waste repository in salt at a proposed site in Deaf Smith County, Texas. The SDG is based on current mining industry standards and practices enhanced to meet the special needs of an underground nuclear waste repository. It provides a common approach for design of both the exploratory and repository shafts. The SDG defines shaft lining and material concepts and presents methods for calculating the loads and displacements that will be imposed on lining structures. It also presents the methodology and formulae for sizing lining components. The SDG directs the shaft designer to sources of geoscience and seismic design data for the Deaf Smith County, Texas repository site. In addition, the SDG describes methods for confirming shaft lining design by means of computer analysis, and it discusses performance monitoring needs that must be considered in the design. 113 refs., 18 figs., 14 tabs

Shared Medical Imaging Repositories.

Science.gov (United States)

Lebre, Rui; Bastião, Luís; Costa, Carlos

2018-01-01

This article describes the implementation of a solution for the integration of ownership concept and access control over medical imaging resources, making possible the centralization of multiple instances of repositories. The proposed architecture allows the association of permissions to repository resources and delegation of rights to third entities. It includes a programmatic interface for management of proposed services, made available through web services, with the ability to create, read, update and remove all components resulting from the architecture. The resulting work is a role-based access control mechanism that was integrated with Dicoogle Open-Source Project. The solution has several application scenarios like, for instance, collaborative platforms for research and tele-radiology services deployed at Cloud.

Characterization of Discharge Areas of Radionuclides Originating From Nuclear Waste Repositories

Science.gov (United States)

Marklund, L.; Xu, S.; Worman, A.

2009-05-01

If leakages in nuclear waste repositories located in crystalline bedrock arise, radionuclides will reach the biosphere and cause a risk of radiological impact. The extent of the radiological impact depends on in which landscape elements the radionuclides emerge. In this study, we investigate if there are certain landscape elements that generally will act as discharge areas for radionuclides leaking from subsurface deposits. We also characterize the typical properties that distinguish these areas from others. In humid regions, landscape topography is the most important driving force for groundwater flow. Because groundwater is the main transporting agent for migrating radionuclides, the topography will determine the flowpaths of leaking radionuclides. How topography and heterogeneities in the subsurface affect the discharge distribution of the radionuclides is therefore an important scope of this study. To address these issues, we developed a 3-D transport model. Our analyses are based on site-specific data from two different areas in Sweden, Forsmark, Uppland, and Oskarshamn, Småland. The Swedish Nuclear Waste Management Company (SKB) has selected these two areas as candidate areas for a deep repository of nuclear waste and the areas are currently subject to site investigations. Our results suggest that there are hot-spots in the landscape i.e. areas with high probability of receiving large amounts of radionuclides from a leaking repository of nuclear waste. The hot-spots concentrate in the sea, streams, lakes and wetlands. All these elements are found at lower elevations in the landscape. This pattern is mostly determined by the landscape topography and the locations of fracture zones. There is a relationship between fracture zones and topography, and therefore the importance of the topography for the discharge area distribution is not contradicted by the heterogeneity in the bedrock. The varieties of landscape elements which have potential for receiving

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

International Nuclear Information System (INIS)

Grams, W.H.

1975-01-01

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

Digital Repositories and the Question of Data Usefulness

Science.gov (United States)

Hughes, J. S.; Downs, R. R.

2017-12-01

The advent of ISO standards for trustworthy long-term digital repositories provides both a set of principles to develop long-term data repositories and the instruments to assess them for trustworthiness. Such mandatory high-level requirements are broad enough to be achievable, to some extent, by many scientific data centers, archives, and other repositories. But the requirement that the data be useful in the future, the requirement that is usually considered to be most relevant to the value of the repository for its user communities, largely remains subject to various interpretations and misunderstanding. However, current and future users will be relying on repositories to preserve and disseminate the data and information needed to discover, understand, and utilize these resources to support their research, learning, and decision-making objectives. Therefore, further study is needed to determine the approaches that can be adopted by repositories to make data useful to future communities of users. This presentation will describe approaches for enabling scientific data and related information, such as software, to be useful for current and potential future user communities and will present the methodology chosen to make one science discipline's data useful for both current and future users. The method uses an ontology-based information model to define and capture the information necessary to make the data useful for contemporary and future users.

Nuclear waste in a repository: amount as a factor in risk duration

International Nuclear Information System (INIS)

Zen, E.

1980-01-01

The relationship between the amount of nuclear waste in a nuclear repository and the safety of the repository is examined. It is shown that the amount of a given hazardous nuclide that is potentially leachable depends on the initial amount of waste in the repository and the time that has elapsed since the repository was put into operation. Nuclear repository safety can be enhanced if repositories are designed as modular units with leach-resistant watertight compartments

Retrievability as proposed in the US repository concept

International Nuclear Information System (INIS)

Harrington, P.G.

2000-01-01

The Nuclear Waste Policy Act states that any repository shall be designed and constructed to permit retrieval. Reasons for retrieval include public health and safety, environmental concerns, and recovery of economically valuable contents of spent nuclear fuel. The Nuclear Regulatory Commission requires that waste must be retrievable at any time up to 50 years after start of emplacement. The US Department of Energy intends to maintain a retrieval capability throughout the preclosure period. Possible preclosure periods range from a minimum of 50 years to as much as 300 years. Repository closure includes sealing all accessible portions of the repository, including ventilation shafts, access ramps and boreholes. Drip shields will be installed over the waste packages. Access to the repository after closure is not intended. The proposed repository includes horizontal emplacement drifts located in the unsaturated zone. The emplacement drift centerline spacing is 81 meters to provide a subboiling region between drifts for water drainage. A drip shield covers the waste packages. All emplacement drifts remain open until closure of the repository, providing performance benefits such as removing heat and moisture during the preclosure period and lowering postclosure temperatures. This does not impede retrieval, permitting a reversal of the emplacement process to accomplish retrieval under normal conditions. The preclosure period is therefore not to enhance retrievability, but does improve performance, and the resultant extension of the retrievability capability is a secondary effect. Information must be provided from the performance confirmation program to support a regulatory decision to close. Closure would isolate the repository from the accessible environment, preclude preferential flowpaths for water into the mountain, and minimize the possibility of inadvertent intrusion. (author)

Staged Repository Development Programmes

International Nuclear Information System (INIS)

Isaacs, T

2003-01-01

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 maximize the

Industrial complementarities between interim storage and reversible geological repository - 59237

International Nuclear Information System (INIS)

Hoorelbeke, Jean-Michel

2012-01-01

The French Act voted in 2006 made the choice of deep geological disposal as the reference option for the long term management of high level (HLW) and intermediate level long-lived waste. The CIGEO repository project aims at avoiding or limiting burden to future generations, which could not be achieved by the extension in time of interim storage. The reversibility as provided by the Act will maintain a liberty of choice for waste management on a duration which is comparable to new storage facility. Interim storage is required to accommodate waste as long as the repository is not available. The commissioning of the repository in 2025 will not suppress needs for interim storage. The paper describes the complementarities between existing and future interim storage facilities and the repository project: repository operational issues and planning, HLW thermal decay, support for the reversibility, etc. It shows opportunities to prepare a global optimization of waste management including the utilization at best of storage capacities and the planning of waste emplacement in the repository in such a way to facilitate operational conditions and to limit cost. Preliminary simulations of storage-disposal scenarios are presented. Thanks to an optimal use of the waste management system, provision can be made for a progressive increase of waste emplacement flow during the first operation phase of the repository. It is then possible to stabilize the industrial activity level of the repository site. An optimal utilization of interim storage can also limit the diversity of waste packages emplaced simultaneously, which facilitates the operation of the repository. 60 years minimum interim storage duration is generally required with respect to HLW thermal output. Extending this interim storage period may reduce the underground footprint of the repository. Regarding reversibility, the capability to manage waste packages potentially retrieved from the repository should be analyzed. The

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

LIFE Materials: Fuel Cycle and Repository Volume 11

International Nuclear Information System (INIS)

Shaw, H.; Blink, J.A.

2008-01-01

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 to meet the thermal constraints of

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...

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...... Trial showed a higher concentration (p studied may explain this...

Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

Science.gov (United States)

Liskay, R.Michael

2014-01-01

Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

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

Reference Design Description for a Geologic Repository

International Nuclear Information System (INIS)

2000-01-01

One of the current major national environmental problems is the safe disposal of large quantities of spent nuclear fuel and high-level radioactive waste materials, which are rapidly accumulating throughout the country. These radioactive byproducts are generated as the result of national defense activities and from the generation of electricity by commercial nuclear power plants. At present, spent nuclear fuel is accumulating at over 70 power plant sites distributed throughout 33 states. The safe disposal of these high-level radioactive materials at a central disposal facility is a high national priority. This Reference Design Description explains the current design for a potential geologic repository that may be located at Yucca Mountain in Nevada for the disposal of spent nuclear fuel and high-level radioactive waste materials. This document describes a possible design for the three fundamental parts of a repository: a surface facility, subsurface repository, and waste packaging. It also presents the current conceptual design of the key engineering systems for the final four phases of repository processes: operations, monitoring, closure, and postclosure. In accordance with current law, this design does not include an interim storage option. In addition, this Reference Design Description reviews the expected long-term performance of the potential repository. It describes the natural barrier system which, together with the engineered systems, achieves the repository objectives. This design will protect the public and the environment by allowing the safe disposal of radioactive waste received from government-owned custodial spent fuel sites, high-level radioactive waste sites, and commercial power reactor sites. All design elements meet or exceed applicable regulations governing the disposal of high-level radioactive waste. The design will provide safe disposal of waste materials for at least a 10,000 year period. During this time interval, natural radioactive decay

Optimizing Resources for Trustworthiness and Scientific Impact of Domain Repositories

Science.gov (United States)

Lehnert, K.

2017-12-01

Domain repositories, i.e. data archives tied to specific scientific communities, are widely recognized and trusted by their user communities for ensuring a high level of data quality, enhancing data value, access, and reuse through a unique combination of disciplinary and digital curation expertise. Their data services are guided by the practices and values of the specific community they serve and designed to support the advancement of their science. Domain repositories need to meet user expectations for scientific utility in order to be successful, but they also need to fulfill the requirements for trustworthy repository services to be acknowledged by scientists, funders, and publishers as a reliable facility that curates and preserves data following international standards. Domain repositories therefore need to carefully plan and balance investments to optimize the scientific impact of their data services and user satisfaction on the one hand, while maintaining a reliable and robust operation of the repository infrastructure on the other hand. Staying abreast of evolving repository standards to certify as a trustworthy repository and conducting a regular self-assessment and certification alone requires resources that compete with the demands for improving data holdings or usability of systems. The Interdisciplinary Earth Data Alliance (IEDA), a data facility funded by the US National Science Foundation, operates repositories for geochemical, marine Geoscience, and Antarctic research data, while also maintaining data products (global syntheses) and data visualization and analysis tools that are of high value for the science community and have demonstrated considerable scientific impact. Balancing the investments in the growth and utility of the syntheses with resources required for certifcation of IEDA's repository services has been challenging, and a major self-assessment effort has been difficult to accommodate. IEDA is exploring a partnership model to share

Long-term environmental impacts of geologic repositories

International Nuclear Information System (INIS)

Pigford, T.H.

1983-05-01

This paper summarizes a study of the long-term environmental impacts of geologic repositories for radioactive wastes. Conceptual repositories in basalt, granite, salt, and tuff were considered. Site-specific hydrological and geochemical parameters were used wherever possible, supplemented with generic parameters when necessary. Radiation doses to future maximally exposed individuals who use the contaminated groundwater and surface water were calculated and compared with a performance criterion of 10 -4 Sv/yr for radiation exposures from probable events. The major contributors to geologic isolation are the absence of groundwater if the repository is in natural salt, the slow dissolution of key radioelements as limited by solubility and by diffusion and convection in groundwater, long water travel times from the waste to the environment, and sorption retardation in the media surrounding the repository. In addition, dilution by surface water can considerably reduce the radiation exposures that result from the small fraction of the waste radioactivity that may ultimately reach the environment. Estimates of environmental impacts are made both for unreprocessed spent fuel and for reprocessing wastes. Accelerated dissolution of waste exposed to groundwater during the period of repository heating is also considered. This study of environmental impacts is a portion of a more comprehensive study of geologic waste disposal carried out by the Waste Isolation System Panel of the US National Research Council

Final repository search together with the citizens. Information, consultation, dialogue, participation

International Nuclear Information System (INIS)

Mueller, Monika C.M.

2013-01-01

The documentation on the Loccum meeting 2013 includes contributions on the following topics: Public participation for the final repository search; Lessons learned from the past; Public participation: what is expected? Experiences of repository operators on public participation; The TRIPLEX concept; From Gorleben to the law on final repository search: a long and a short story; Public participation concerning radioactive waste storage; The public has to be informed on the radioactive waste problem and the possible solutions; After consensus is before consensus - German final repository conflict between legislation and simulated public participation; Political concept of public participation; A fast final repository law will not bring about social peace; Good public participation on final repository search - requirements, challenges, questions and approaches.

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Science.gov (United States)

Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

2016-10-01

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computational Materials Repository

DEFF Research Database (Denmark)

Landis, David

, different abstraction levels and enables users to analyze their own results, and allows to share data with collaborators. The approach of the Computational Materials Repository (CMR) is to convert data to an internal format that maintains the original variable names without insisting on any semantics...

Geotechnical instrumentation for repository shafts

International Nuclear Information System (INIS)

Lentell, R.L.; Byrne, J.

1993-01-01

The US Congress passed the Nuclear Waste Policy Act in 1980, which required that three distinctly different geologic media be investigated as potential candidate sites for the permanent disposal of high-level nuclear waste. The three media that were selected for study were basalt (WA), salt (TX, LA, MS, UT), and tuff (NV). Preliminary Exploratory Shaft Facilities (ESF) designs were prepared for seven candidate salt sites, including bedded and domal salt environments. A bedded-salt site was selected in Deaf Smith County, TX for detailed site characterization studies and ESF Final Design. Although Congress terminated the Salt Repository Program in 1988, Final Design for the Deaf Smith ESF was completed, and much of the design rationale can be applied to subsequent deep repository shafts. This paper presents the rationale for the geotechnical instrumentation that was designed for construction and operational performance monitoring of the deep shafts of the in-situ test facility. The instrumentation design described herein can be used as a general framework in designing subsequent instrumentation programs for future high-level nuclear waste repository shafts

Safety case for Slovenian LILW near-surface repository

International Nuclear Information System (INIS)

Viršek, Sandi; Špiler, Janja; Žagar, Tomaž

2016-01-01

Conclusions: • Repository provides the fulfillment of international and national legal requirements regarding treatment and disposal of LILW; • Repository improves the conditions for life extension for NPP Krško and offers synergetic effects for the second unit of NPP Krško; • Repository provides a basis for safe, economic and reliable use of radioactive sources in science, medicine and industry in Slovenia; • All economic calculations and comparisons show a clear advantage in case of a joint Slovenian and Croatian solution

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.

In Vivo Immunomodulation and Lipid Peroxidation Activities Contributed to Chemoprevention Effects of Fermented Mung Bean against Breast Cancer

Directory of Open Access Journals (Sweden)

Swee Keong Yeap

2013-01-01

Full Text Available Mung bean has been reported to have antioxidant, cytotoxic, and immunomodulatory effects in vitro. Fermented products are reported to have enhanced immunomodulation and cancer chemopreventive effects. In this study, fermented mung bean treatments in vivo were studied by monitoring tumor development, spleen immunity, serum cytokine (interleukin 2 and interferon gamma levels, and spleen/tumor antioxidant levels after injection with low and high risk 4T1 breast cancer cells. Pretreatment with fermented mung bean was associated with delayed tumor formation in low risk mice. Furthermore, this treatment was connected with higher serum anticancer cytokine levels, spleen T cell populations, splenocyte cytotoxicity, and spleen/tumor antioxidant levels. Histopathological evaluation of fermented mung bean treated tumor revealed lower event of mitotic division. On the other hand, antioxidant and nitric oxide levels that were significantly increased in the untreated mice were inhibited in the fermented mung bean treated groups. These results suggested that fermented mung bean has potential cancer chemoprevention effects through the stimulation of immunity, lipid peroxidation, and anti-inflammation.

Impact of retrievability of repository design

International Nuclear Information System (INIS)

Heijdra, J.J.; Gaag, J. v.d.; Prij, J.

1995-01-01

In this paper the impact of the retrievability on the design of the repository will be handled. Retrievability of radioactive waste from a repository in geological formations has received increasing attention during recent years. It is obvious that this retrievability will have consequences in terms of mining engineering, safety and cost. The purpose of the present study is to evaluate cost consequences by comparing two extreme options for retrievable storage. (author). 6 refs., 3 figs

Chemical risks from nuclear waste repositories

International Nuclear Information System (INIS)

Persson, L.

1988-01-01

Studies concerning the chemical risks of nuclear waste are reviewed. The radiological toxicity of the material is of primary concern but the potential nonradiological toxicity should not be overlooked as the chemotoxic substances may reach the biosphere from a nuclear waste repository. In the report is concluded that the possible chemotoxic effects of a repository for nuclear waste should be studied as a part of the formal risk assessment of the disposal concept. (author)

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...

Repository waste-handling operations, 1998

International Nuclear Information System (INIS)

Cottam, A.E.; Connell, L.

1986-04-01

The Civilian Radioactive Waste Management Program Mission Plan and the Generic Requirements for a Mined Geologic Disposal System state that beginning in 1998, commercial spent fuel not exceeding 70,000 metric tons of heavy metal, or a quantity of solidified high-level radioactive waste resulting from the reprocessing of such a quantity of spent fuel, will be shipped to a deep geologic repository for permanent storage. The development of a waste-handling system that can process 3000 metric tons of heavy metal annually will require the adoption of a fully automated approach. The safety and minimum exposure of personnel will be the prime goals of the repository waste handling system. A man-out-of-the-loop approach will be used in all operations including the receipt of spent fuel in shipping casks, the inspection and unloading of the spent fuel into automated hot-cell facilities, the disassembly of spent fuel assemblies, the consolidation of fuel rods, and the packaging of fuel rods into heavy-walled site-specific containers. These containers are designed to contain the radionuclides for up to 1000 years. The ability of a repository to handle more than 6000 pressurized water reactor spent-fuel rods per day on a production basis for approximately a 23-year period will require that a systems approach be adopted that combines space-age technology, robotics, and sophisticated automated computerized equipment. New advanced inspection techniques, maintenance by robots, and safety will be key factors in the design, construction, and licensing of a repository waste-handling facility for 1998

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.

Ventilation planning for a prospective nuclear waste repository

International Nuclear Information System (INIS)

Wallace, K.G. Jr.

1987-01-01

In 1982, the US Congress passed the Nuclear Waste Policy Act to provide for the development of underground repositories for spent nuclear fuel. This development will be managed by the United States Department of Energy. In 1986, the President selected three areas for site characterization to determine their suitability for the development of an underground repository; those sites were: (1) A site in volcanic tuff located at Yucca Mountain in Nevada, (2) a site in bedded salt located in Deaf Smith County in Texas, and (3) a site in basalt located in Hanford, Washington. At present conceptual repository designs are being developed for each site. A key element of a repository design is the underground ventilation system required to support construction, nuclear waste emplacement, and potential waste retrieval. This paper describes the preliminary ventilation systems designed for the repository in tuff. The concept provides separate ventilation systems for the construction and waste emplacement activities. The paper further describes the means by which acceptable environmental conditions will be re-established to allow re-entry into previously closed rooms for the purpose of inspection, maintenance or retrieval

Status of the implementation of Brazilian National Repository

International Nuclear Information System (INIS)

Tello, Cledola Cassia Oliveira de

2015-01-01

In Brazil, the use of nuclear energy and radioisotopes is increasing and it already justifies the construction of a national repository for radioactive wastes of low and intermediate-level. The Brazilian National Commission for Nuclear Energy (CNEN) is legally responsible for designing and constructing intermediate and final storages for radioactive wastes generated in all Country, in accordance to Federal Law No. 10308. Additionally, the Brazilian Environmental Regulator (IBAMA) lately is imposing to the implementation of new nuclear installations (e.g. Angra 3 NPP and Brazilian Multipurpose Reactor) that the National Repository should be in construction, before the start-up of those ones. In November 2009, the RBMN Project Charter was signed. The RBMN Project aims at the implantation of a National Repository to dispose the radioactive wastes of low- and intermediate-level. Some aspects about the Repository construction are very challenging, mainly due to the licensing process, which will be made for two different regulatory bodies, nuclear and environmental. The main achievements obtained till now are the establishment of the current Brazilian radioactive waste inventory, the conceptual design and the selection of candidate sites for the repository. The current status of the Project is summarized. (author)

A Repository of Semantic Open EHR Archetypes

Directory of Open Access Journals (Sweden)

Fernando Sánchez

2015-03-01

Full Text Available This paper describes a repository of openEHR archetypes that have been translated to OWL. In the work presented here, five different CKMs (Clinical Knowledge Managers have been downloaded and the archetypes have been translated to OWL. This translation is based on an existing translator that has been improved to solve programming problems with certain structures. As part of the repository a tool has been developed to keep it always up-to-date. So, any change in one of the CKMs (addition, elimination or even change of an archetype will involve translating the changed archetypes once more. The repository is accessible through a Web interface (http://www.openehr.es/.

Low- and intermediate-level waste repository-induced effects

Energy Technology Data Exchange (ETDEWEB)

Leupin, O.X.; Marschall, P.; Johnson, L.; Cloet, V.; Schneider, J. [National Cooperative for the Disposal of Radioactive Waste (NAGRA), Wettingen (Switzerland); Smith, P. [Safety Assessment Management Ltd, Henley-On-Thames, Oxfordshire (United Kingdom); Savage, D. [Savage Earth Associates Ltd, Bournemouth, Dorset (United Kingdom); Senger, R. [Intera Inc., Ennetbaden (Switzerland)

2016-10-15

This status report aims at describing and assessing the interactions of the radioactive waste emplaced in a low- and intermediate level waste (L/ILW) repository with the engineered materials and the Opalinus Clay host rock. The Opalinus Clay has a thickness of about 100 m in the proposed siting regions. Among other things the results are used to steer the RD and D programme of NAGRA. The repository-induced effects considered in this report are of the following broad types: - Thermal effects: i.e. effects arising principally from the heat generated by the waste and the setting of cement. - Rock-mechanical effects: i.e. effects arising from the mechanical disturbance to the rock caused by the excavation of the emplacement caverns and other underground structures. - Hydraulic and gas-related effects: i.e. the effects of repository resaturation and of gas generation, e.g. due to the corrosion of metals within the repository, on the host rock and engineered barriers. - Chemical effects: i.e. chemical interactions between the waste, the engineered materials and the host rock. Deep geological repositories are designed to avoid or mitigate the impact of potentially detrimental repository-induced effects on long-term safety. For the repository under consideration in the present report, an assessment of those repository-induced effects that remain shows that detrimental chemical and mechanical impacts are largely confined to the rock adjacent to the excavations, thermal impacts are minimal and gas effects can be mitigated by appropriate design measures to reduce gas production and provide pathways for gas transport that limit gas pressure build-up (engineered gas transport system, or EGTS). Specific measures that are part of the current reference design are discussed in relation to their significance with respect to repository-induced effects. The disposal system described in this report provides a system of passive barriers with multiple safety functions. The disposal

Low- and intermediate-level waste repository-induced effects

International Nuclear Information System (INIS)

Leupin, O.X.; Marschall, P.; Johnson, L.; Cloet, V.; Schneider, J.; Smith, P.; Savage, D.; Senger, R.

2016-10-01

This status report aims at describing and assessing the interactions of the radioactive waste emplaced in a low- and intermediate level waste (L/ILW) repository with the engineered materials and the Opalinus Clay host rock. The Opalinus Clay has a thickness of about 100 m in the proposed siting regions. Among other things the results are used to steer the RD and D programme of NAGRA. The repository-induced effects considered in this report are of the following broad types: - Thermal effects: i.e. effects arising principally from the heat generated by the waste and the setting of cement. - Rock-mechanical effects: i.e. effects arising from the mechanical disturbance to the rock caused by the excavation of the emplacement caverns and other underground structures. - Hydraulic and gas-related effects: i.e. the effects of repository resaturation and of gas generation, e.g. due to the corrosion of metals within the repository, on the host rock and engineered barriers. - Chemical effects: i.e. chemical interactions between the waste, the engineered materials and the host rock. Deep geological repositories are designed to avoid or mitigate the impact of potentially detrimental repository-induced effects on long-term safety. For the repository under consideration in the present report, an assessment of those repository-induced effects that remain shows that detrimental chemical and mechanical impacts are largely confined to the rock adjacent to the excavations, thermal impacts are minimal and gas effects can be mitigated by appropriate design measures to reduce gas production and provide pathways for gas transport that limit gas pressure build-up (engineered gas transport system, or EGTS). Specific measures that are part of the current reference design are discussed in relation to their significance with respect to repository-induced effects. The disposal system described in this report provides a system of passive barriers with multiple safety functions. The disposal

Making research data repositories visible: the re3data.org Registry.

Directory of Open Access Journals (Sweden)

Heinz Pampel

Full Text Available Researchers require infrastructures that ensure a maximum of accessibility, stability and reliability to facilitate working with and sharing of research data. Such infrastructures are being increasingly summarized under the term Research Data Repositories (RDR. The project re3data.org-Registry of Research Data Repositories-has begun to index research data repositories in 2012 and offers researchers, funding organizations, libraries and publishers an overview of the heterogeneous research data repository landscape. In July 2013 re3data.org lists 400 research data repositories and counting. 288 of these are described in detail using the re3data.org vocabulary. Information icons help researchers to easily identify an adequate repository for the storage and reuse of their data. This article describes the heterogeneous RDR landscape and presents a typology of institutional, disciplinary, multidisciplinary and project-specific RDR. Further the article outlines the features of re3data.org, and shows how this registry helps to identify appropriate repositories for storage and search of research data.

Making research data repositories visible: the re3data.org Registry.

Science.gov (United States)

Pampel, Heinz; Vierkant, Paul; Scholze, Frank; Bertelmann, Roland; Kindling, Maxi; Klump, Jens; Goebelbecker, Hans-Jürgen; Gundlach, Jens; Schirmbacher, Peter; Dierolf, Uwe

2013-01-01

Researchers require infrastructures that ensure a maximum of accessibility, stability and reliability to facilitate working with and sharing of research data. Such infrastructures are being increasingly summarized under the term Research Data Repositories (RDR). The project re3data.org-Registry of Research Data Repositories-has begun to index research data repositories in 2012 and offers researchers, funding organizations, libraries and publishers an overview of the heterogeneous research data repository landscape. In July 2013 re3data.org lists 400 research data repositories and counting. 288 of these are described in detail using the re3data.org vocabulary. Information icons help researchers to easily identify an adequate repository for the storage and reuse of their data. This article describes the heterogeneous RDR landscape and presents a typology of institutional, disciplinary, multidisciplinary and project-specific RDR. Further the article outlines the features of re3data.org, and shows how this registry helps to identify appropriate repositories for storage and search of research data.

Exploring Characterizations of Learning Object Repositories Using Data Mining Techniques

Science.gov (United States)

Segura, Alejandra; Vidal, Christian; Menendez, Victor; Zapata, Alfredo; Prieto, Manuel

Learning object repositories provide a platform for the sharing of Web-based educational resources. As these repositories evolve independently, it is difficult for users to have a clear picture of the kind of contents they give access to. Metadata can be used to automatically extract a characterization of these resources by using machine learning techniques. This paper presents an exploratory study carried out in the contents of four public repositories that uses clustering and association rule mining algorithms to extract characterizations of repository contents. The results of the analysis include potential relationships between different attributes of learning objects that may be useful to gain an understanding of the kind of resources available and eventually develop search mechanisms that consider repository descriptions as a criteria in federated search.

Radiosensitivity of microorganisms isolated from radioactive waste repository

International Nuclear Information System (INIS)

Gazso, Lajos

2001-01-01

established. The gases produced by the gasforming isolates were CO 2 and H 2 (anaerobic isolates). About 20% of the aerobic isolates produced siderophores. The highest proportions of organic acid producers in the aerobic and anaerobic isolates from the air samples were 63 % and 54 %, respectively. The radiosensitivity of the aerobic isolates was also determined, the D10 values of the spore-formers ranges between 0.8-2.44 kGy. Our results indicate that the sulfate-reducing bacteria and production of complexing agents may contribute to the mobilization of radionuclides in underground repository. Although our findings contribute to an understanding of the impact of microbial activity on radioactive waste repository, we do not as yet have enough information to develop a model which will predict the consequences of these processes. Future investigation will focus on specific questions such as the effect of biofilms on radionuclide migration and the uptake and accumulation of cations by the isolated bacteria. These processes should be evaluated for the long term safe disposal. (author)

Studies on an advanced repository system with enhanced engineered barriers (a framework)

International Nuclear Information System (INIS)

Fujiwara, A.; Tashiro, S.; Ikari, S.; Suzuki, A.

1993-01-01

In order to propose advanced designs of repositories with enhanced engineered barriers of relatively high radioactive wastes such as burnable poisons, channel boxes, control rods and highly irradiated metals, studies started in 1987 and completed the first phase in 1992. This paper presents the framework and brief results of the first phase. The studies set preliminary design concepts of the repositories with various combinations with engineered barriers and natural barriers for different models and locations such as a silo type in shallow land or a tunnel type in intermediate depth. Through the designs, four component technics were picked up and studied for (1) construction of the components in repository; (2) performance evaluation to realize repository design; (3) improvement of circumstances inside or around repository; and (4) surveillance of repository performance to realize the repository designs. Finally, some repository systems were provided using obtained results, and then the applicability and the economy were evaluated. The studies will continue to the second phase focusing on the long-term performance of the repositories

Visual querying and analysis of large software repositories

NARCIS (Netherlands)

Voinea, Lucian; Telea, Alexandru

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

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…

The Use of Digital Repositories for Enhancing Teacher Pedagogical Performance

Science.gov (United States)

Cohen, Anat; Kalimi, Sharon; Nachmias, Rafi

2013-01-01

This research examines the usage of local learning material repositories at school, as well as related teachers' attitudes and training. The study investigates the use of these repositories for enhancing teacher performance and assesses whether the assimilation of the local repositories increases their usage of and contribution to by teachers. One…

Oceanographic Data Repositories: An Analysis of the International Situation

Directory of Open Access Journals (Sweden)

Fabiano Couto Corrêa da Silva

2017-04-01

Full Text Available The preservation and organization of oceanographic research data enables the scientific community to consult and reuse information of different kinds, and this is made possible by the repositories, meaning the services that facilitate data storage and dissemination. This paper reviews the current situation of oceanographic data repositories across different countries and evaluates them according to a series of indicators. The writers propose that although interest in storing and reusing oceanographic data has increased in recent years, the repositories are still in the process of developing their systems for processing, disseminating and reusing data. The repositories also differ in terms of architecture and the organizational level of the content they offer.

Keratinocyte proliferation, differentiation, and apoptosis-Differential mechanisms of regulation by curcumin, EGCG and apigenin

International Nuclear Information System (INIS)

Balasubramanian, Sivaprakasam; Eckert, Richard L.

2007-01-01

We have proposed that it is important to examine the impact of chemopreventive agents on the function of normal human epidermal keratinocytes since these cells comprise the barrier that protects the body from a range of environmental insults. In this context, it is widely appreciated that cancer may be retarded by consumption or topical application of naturally occurring food-derived chemopreventive agents. Our studies show that (-)-epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, acts to enhance the differentiation of normal human keratinocytes as evidenced by its ability to increase involucrin (hINV), transglutaminase type 1 (TG1) and caspase-14 gene expression. EGCG also stimulates keratinocyte morphological differentiation. These actions of EGCG are mediated via activation of a nPKC, Ras, MEKK1, MEK3, p38δ-ERK1/2 signaling cascade which leads to increased activator protein 1 (AP1) and CAATT enhancer binding protein (C/EBP) transcription factor expression, increased binding of these factors to DNA, and increased gene transcription. In contrast, apigenin, a dietary flavonoid derived from plants and vegetables, and curcumin, an agent derived from turmeric, inhibit differentiation by suppressing MAPK signal transduction and reducing API transcription factor level. Curcumin also acts to enhance apoptosis, although EGCG and apigenin do not stimulate apoptosis. In addition, all of these agents inhibit keratinocyte proliferation. These findings indicate that each of these diet-derived chemopreventive agents has a profound impact on normal human keratinocyte function and that they operate via distinct and sometimes opposing mechanisms. However, all are expected to act as chemopreventive agents

Microbial Influence on the Performance of Subsurface, Salt-Based Radioactive Waste Repositories. An Evaluation Based on Microbial Ecology, Bioenergetics and Projected Repository Conditions

International Nuclear Information System (INIS)

Swanson, J.S.; Reed, D.T.; Cherkouk, A.; Arnold, T.; Meleshyn, A.; Patterson, Russ

2018-01-01

For the past several decades, the Nuclear Energy Agency Salt Club has been supporting and overseeing the characterisation of rock salt as a potential host rock for deep geological repositories. This extensive evaluation of deep geological settings is aimed at determining - through a multidisciplinary approach - whether specific sites are suitable for radioactive waste disposal. Studying the microbiology of granite, basalt, tuff, and clay formations in both Europe and the United States has been an important part of this investigation, and much has been learnt about the potential influence of microorganisms on repository performance, as well as about deep subsurface microbiology in general. Some uncertainty remains, however, around the effects of microorganisms on salt-based repository performance. Using available information on the microbial ecology of hyper-saline environments, the bioenergetics of survival under high ionic strength conditions and studies related to repository microbiology, this report summarises the potential role of microorganisms in salt-based radioactive waste repositories

Effects of repository conditions on environmental impact reduction by recycling

International Nuclear Information System (INIS)

Ahn, Joonhong

2010-01-01

The environmental impacts (EI) of high-level wastes (HLW) disposed of in a water-saturated repository (WSR) and in the Yucca Mountain Repository (YMR) for various fuel cycle cases have been evaluated and compared to observe the difference in the recycling effects for differing repository conditions. With the impacts of direct spent fuel disposal in each repository as the reference level, separation of actinides by Urex+ and borosilicate vitrification clearly reduces the environmental impacts of YMR, while separation by Purex and borosilicate vitrification would not necessarily reduce the environmental impact of WSR. (authors)

NPP Krsko: LILW Repository or Long Term Storage

International Nuclear Information System (INIS)

Lokner, V.; Subasic, D.; Levanat, I.

2008-01-01

Construction of the facilities for LILW and SF management, as planned in Decommissioning and LILW and SF management program for NPP Krsko, would be a rather expensive and challenging project for such a small nuclear program. In order to accommodate waste arising from a single nuclear power plant, one LILW repository should be constructed before the end of the NPP operation, then one SF dry storage, and finally one geological repository. This requires relatively urgent identification within Slovenian/Croatian territory of three locations that meet the criteria for establishment of such facilities and are acceptable to the local communities. There are very few such potential locations. The siting process for the first of the three facilities is well under way in Slovenia, because the country wants to have its LILW repository in operation by the year 2013. In order to facilitate public acceptance, Slovenian government has introduced financial incentives to local communities for the repository construction and operation. These 'compensations for limited land use' may significantly increase the overall costs of disposal if the repository is in operation for a long period. In the recent years, however, a possibility of long term storage (LTS) is gaining an increased attention in the waste management community, and has already been introduced e.g. in the Netherlands. It is a particularly viable option for limited waste quantities. Disposal remains the final solution, but present technologies have made possible a relatively inexpensive storage up to about hundred years, which can accommodate LILW, HLW and SF from nuclear programs as well as research reactor waste and NORM. Such storage would be a safe and simple temporary solution, encompassing all immediate and near future waste management needs. In addition, it would increase flexibility and reduce financing requirements for the final waste disposal: providing additional time for reduction of radiation emission and heat

Czech Republic. Dukovany repository

International Nuclear Information System (INIS)

2001-01-01

Full text: The repository at the Dukovany site is a structure located above the land surface. It consists of two double-rows of reinforced concrete vaults. Each double-row has dimensions 38x160x6 meters and contains 2x28 vaults. The internal dimensions of each vault are 18x6x5.4 meters. The repository serves for reactor wastes from the Dukovany and Temelin nuclear power plants (NPPs). Its capacity is 55,000 m 3 or 130,000 drums. The repository is a fully engineered facility with multiple barriers. The first engineered barrier is the waste form (in the case of waste from the Dukovany NPP, the waste form is mainly bitumen, but concrete and glass are also considered as suitable solidification products). The second barrier is the container (a 200 litre steel drum or a HIC container), whereas the third consists of cut-off reinforced concrete walls with asphalt-based hydro-insulation. The fourth barrier is a cap which should protect the vaults against infiltration of rainwater and should serve also as an intrusion and erosion barrier. The fifth barrier is a drainage system around the repository which is composed of layers of gravel and sand. The void space in drums around the waste is filled with specially composed grout. Such waste packages are emplaced into the disposal vault, which is covered by pre-fabricated panels. Thereafter, joints between the panels are sealed and a provisional coverage added; the final cover, however, will be constructed only over the whole row of 28 vaults, until all vaults are filled with waste. The final cover will encompass the following components: reinforced concrete pre-fabricated panels (500 mm); cement overcoat (30 mm); insulation foil; concrete layer for cap levelling (5-150 mm); layer of asphalto-propylene concrete (150 mm); soil (450 mm); geotextile foil with topsoil (top surface vegetation). (author)

Monitored retrievable storage (MRS) facility and salt repository integration: Engineering study report

International Nuclear Information System (INIS)

1987-07-01

This MRS Facility and Salt Repository Integration Study evaluates the impacts of an integrated MRS/Salt Repository Waste Management System on the Salt Repository Surface facilities' design, operations, cost, and schedule. Eight separate cases were studied ranging from a two phase repository design with no MRS facility to a design in which the repository only received package waste from the MRS facility for emplacement. The addition of the MRS facility to the Waste Management System significantly reduced the capital cost of the salt repository. All but one of the cases studied were capable of meeting the waste acceptance data. The reduction in the size and complexity of the Salt Repository waste handling building with the integration of the MRS facility reduces the design and operating staff requirements. 7 refs., 35 figs., 43 tabs

Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice.

Science.gov (United States)

Nasr, Magda; Selima, Eman; Hamed, Omar; Kazem, Amany

2014-01-15

No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic agents: leflunomide; a disease modifying antirheumatic drug, perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice. Eight weeks following DEN administration, there was a significant rise in immunohistochemical staining of CD31-positive endothelial cells and consequently hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was associated with elevation in hepatic vascular endothelial growth factor (VEGF) level as compared to normal controls (Pcurcumin alone abrogated the DEN-induced increased MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF-1α hepatic expression. Combination of these agents showed further inhibitory action on neovascularization and synergistic attenuation of hepatic VEGF (1954.27±115pg/ml) when compared to each single agent. Histopathological examination revealed a more beneficial chemopreventive activity in the combination group compared to each monotherapy. In conclusion, the combination treatment of leflunomide, perindopril and curcumin targeting different angiogenic pathways, resulted in synergistic inhibition of angiogenesis and consequently more effective chemoprevention of HCC. © 2013 Published by Elsevier B.V.

Monte Carlo simulations for generic granite repository studies

Energy Technology Data Exchange (ETDEWEB)

Chu, Shaoping [Los Alamos National Laboratory; Lee, Joon H [SNL; Wang, Yifeng [SNL

2010-12-08

In a collaborative study between Los Alamos National Laboratory (LANL) and Sandia National Laboratories (SNL) for the DOE-NE Office of Fuel Cycle Technologies Used Fuel Disposition (UFD) Campaign project, we have conducted preliminary system-level analyses to support the development of a long-term strategy for geologic disposal of high-level radioactive waste. A general modeling framework consisting of a near- and a far-field submodel for a granite GDSE was developed. A representative far-field transport model for a generic granite repository was merged with an integrated systems (GoldSim) near-field model. Integrated Monte Carlo model runs with the combined near- and farfield transport models were performed, and the parameter sensitivities were evaluated for the combined system. In addition, a sub-set of radionuclides that are potentially important to repository performance were identified and evaluated for a series of model runs. The analyses were conducted with different waste inventory scenarios. Analyses were also conducted for different repository radionuelide release scenarios. While the results to date are for a generic granite repository, the work establishes the method to be used in the future to provide guidance on the development of strategy for long-term disposal of high-level radioactive waste in a granite repository.

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.

Monitoring of geological repositories for high level radioactive waste

International Nuclear Information System (INIS)

2001-04-01

Geological repositories for disposal of high level radioactive waste are designed to provide isolation of the waste from human environment for many thousands of years. This report discusses the possible purposes for monitoring geological repositories at the different stages of a repository programme, the use that may be made of the information obtained and the techniques that might be applied. This report focuses on the different objectives that monitoring might have at various stages of a programme, from the initiation of work on a candidate site, to the period after repository closure. Each objective may require somewhat different types of information, or may use the same information in different ways. Having evaluated monitoring requirements, the report concludes with a brief evaluation of available monitoring techniques

Integrating repositories with fuel cycles: The airport authority model

Energy Technology Data Exchange (ETDEWEB)

Forsberg, C. [Massachusetts Inst. of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States)

2012-07-01

The organization of the fuel cycle is a legacy of World War II and the cold war. Fuel cycle facilities were developed and deployed without consideration of the waste management implications. This led to the fuel cycle model of a geological repository site with a single owner, a single function (disposal), and no other facilities on site. Recent studies indicate large economic, safety, repository performance, nonproliferation, and institutional incentives to collocate and integrate all back-end facilities. Site functions could include geological disposal of spent nuclear fuel (SNF) with the option for future retrievability, disposal of other wastes, reprocessing with fuel fabrication, radioisotope production, other facilities that generate significant radioactive wastes, SNF inspection (navy and commercial), and related services such as SNF safeguards equipment testing and training. This implies a site with multiple facilities with different owners sharing some facilities and using common facilities - the repository and SNF receiving. This requires a different repository site institutional structure. We propose development of repository site authorities modeled after airport authorities. Airport authorities manage airports with government-owned runways, collocated or shared public and private airline terminals, commercial and federal military facilities, aircraft maintenance bases, and related operations - all enabled and benefiting the high-value runway asset and access to it via taxi ways. With a repository site authority the high value asset is the repository. The SNF and HLW receiving and storage facilities (equivalent to the airport terminal) serve the repository, any future reprocessing plants, and others with needs for access to SNF and other wastes. Non-public special-built roadways and on-site rail lines (equivalent to taxi ways) connect facilities. Airport authorities are typically chartered by state governments and managed by commissions with members

Integrating repositories with fuel cycles: The airport authority model

International Nuclear Information System (INIS)

Forsberg, C.

2012-01-01

The organization of the fuel cycle is a legacy of World War II and the cold war. Fuel cycle facilities were developed and deployed without consideration of the waste management implications. This led to the fuel cycle model of a geological repository site with a single owner, a single function (disposal), and no other facilities on site. Recent studies indicate large economic, safety, repository performance, nonproliferation, and institutional incentives to collocate and integrate all back-end facilities. Site functions could include geological disposal of spent nuclear fuel (SNF) with the option for future retrievability, disposal of other wastes, reprocessing with fuel fabrication, radioisotope production, other facilities that generate significant radioactive wastes, SNF inspection (navy and commercial), and related services such as SNF safeguards equipment testing and training. This implies a site with multiple facilities with different owners sharing some facilities and using common facilities - the repository and SNF receiving. This requires a different repository site institutional structure. We propose development of repository site authorities modeled after airport authorities. Airport authorities manage airports with government-owned runways, collocated or shared public and private airline terminals, commercial and federal military facilities, aircraft maintenance bases, and related operations - all enabled and benefiting the high-value runway asset and access to it via taxi ways. With a repository site authority the high value asset is the repository. The SNF and HLW receiving and storage facilities (equivalent to the airport terminal) serve the repository, any future reprocessing plants, and others with needs for access to SNF and other wastes. Non-public special-built roadways and on-site rail lines (equivalent to taxi ways) connect facilities. Airport authorities are typically chartered by state governments and managed by commissions with members

Overly Honest Data Repository Development

Directory of Open Access Journals (Sweden)

Colleen Fallaw

2016-10-01

Full Text Available After a year of development, the library at the University of Illinois at Urbana-Champaign has launched a repository, called the Illinois Data Bank (https://databank.illinois.edu/, to provide Illinois researchers with a free, self-serve publishing platform that centralizes, preserves, and provides persistent and reliable access to Illinois research data. This article presents a holistic view of development by discussing our overarching technical, policy, and interface strategies. By openly presenting our design decisions, the rationales behind those decisions, and associated challenges this paper aims to contribute to the library community's work to develop repository services that meet growing data preservation and sharing needs.

Initial design process of the repository

International Nuclear Information System (INIS)

Osmanlioglu, A.E.

2001-01-01

The concept of the final disposal of high level wastes is to isolate the waste from the biosphere for extremely long periods of time by emplacement of wastes into deep stable geological formations. Several geological formations have been considered as candidate host environments for high level waste disposal and several techniques have been developed for repository design. In this study, interrelationships of main parameters of a general repository design have been defined and effective parameters are shown at each step. Initial design process is based on the long term stability of underground openings as disposal galleries. For this reason, this design process includes two main analyses: mechanical analysis and thermal analysis. Each of the analysis systems is directly related to each other by technical precautions. As a result of this design process, general information about the acceptable depth of the repository, layout and emplacement pattern can be taken. Final design study can be established on the result of initial design process. (author)

The deep geologic repository technology programme: toward a geoscience basis for understanding repository safety

International Nuclear Information System (INIS)

Jensen, M.R.

2007-01-01

Within the Deep Geologic Repository Technology Programme (DGRTP) several Geoscience activities are focused on advancing the understanding of groundwater flow system evolution and geochemical stability in a Canadian Shield setting as affected by long-term climate change. A key aspect is developing confidence in predictions of groundwater flow patterns and residence times as they relate to the safety of a deep geologic repository for used nuclear fuel waste. This is being achieved through a coordinated multi-disciplinary approach intent on: i) demonstrating coincidence between independent geo-scientific data; ii) improving the traceability of geo-scientific data and its interpretation within a conceptual descriptive model(s); iii) improving upon methods to assess and demonstrate robustness in flow domain prediction(s) given inherent flow domain uncertainties (i.e. spatial chemical/physical property distributions, boundary conditions) in time and space; and iv) improving awareness amongst geo-scientists as to the utility of various geo-scientific data in supporting a safety case for a deep geologic repository. This multi-disciplinary DGRTP approach is yielding an improved understanding of groundwater flow system evolution and stability in Canadian Shield settings that is further contributing to the geo-scientific basis for understanding and communicating aspects of DGR safety. (author)

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…

General construction requirements for the deep repository in the KBS-3 system

International Nuclear Information System (INIS)

2002-10-01

The KBS-3 systems includes equipment and plants for transport of spent nuclear fuels and encapsulated spent fuels, central intermediate storage, encapsulation and deep geologic disposal. The requirements in this document concern the repository and have been put together in view of the tasks of designing, constructing and building the repository. The report presents: A general review of existing design plans; Laws and regulations relevant for the design of the repository; How the regulations have been broken down to functional demands and dimensioning requirements for the repository; How the site conditions influence the design, and how the layout of the different parts of the repository interact; Relations between the functions of the repository, the safety and the design; A foundation for developing construction plans for the repository. The requirements will be collected in a database that will develop as new knowledge is collected

Global thermo-mechanical effects from a KBS-3 type repository

International Nuclear Information System (INIS)

Hakami, E.; Olofsson, Stig-Olof

1998-01-01

The objective of this study has been to identify the global thermo-mechanical effects in the bedrock hosting a nuclear waste repository. Numerical thermo-mechanical modeling using distinct element models was performed. The number of fracture zones, the heat intensity of the waste, the material properties of the rock mass and the boundary conditions of the models were varied. Different models for multi-level repositories were also analyzed and compared to the main single-level case. Further, the global influence from the excavation of repository tunnels and deposition holes was examined by introducing weaker rock mass material properties in the repository region of one model. The maximum compression stress obtained for the main model is 44 MPa and occurs at the repository level after about 100 years of deposition. Due to thermal expansion, the rock mass displaces upward, and the maximum heave at the ground surface after 1000 years is calculated to be 16 cm. In the area close to the ground surface the horizontal stresses reduce, causing the rock to yield in tension down to a depth of about 80 meters. The fracture zones show opening displacements at shallow depths and closing and shearing at the repository level. The maximum displacements are 0.3-2.5 cm for closing, 0.0-0.8 cm for opening and 0.2-2.2 cm for shearing. The resultant stresses and displacements depend in large part on the assumptions made concerning the heat intensity of the waste. In the main model, an initial heat intensity of 10 W/m 2 is assumed, which gives larger effects than the case with 6 W/m 2 . Another important input parameter for the analysis is the Young's modulus of the rock mass. In the main model, a value of 30 GPa is assumed. Higher values of Young's modulus give larger thermo-mechanical effects. All multi-level repository layouts give rise to higher temperatures than the single-level layout, causing the compressive stresses to increase more at the repository level. The multi

Underground excavation methods for a high-level waste repository

International Nuclear Information System (INIS)

Peshel, J.; Gupta, D.; Nataraja, M.

1990-01-01

This paper reports on rock excavation methods for a High-Level Waste repository that should be selected to limit the potential for creating preferential pathways for groundwater to travel to the waste packages or for radionuclides to migrate to the accessible environment. The use of water and other foreign substances should be controlled so that the repository performance is not compromised. The excavated openings should remain stable so that operations can be carried out safely and the retrievability option maintained. As per the current conceptual designs presented by the Department of Energy, the exploratory shaft facility becomes a part of the repository if the Yucca Mountain site is found suitable for repository development. Therefore, the methods of constructing the underground openings should be compatible with the performance requirements for the repository. Also, the degree of damage to the rock surrounding the openings and the extent of the damage zone should not preclude adequate site characterization. The ESf construction and operation should be compatible with the site data gathering activities, such as geological, thermomechanical, hydrological and geochemical testing

Reference design description for a geologic repository. Revision 02

International Nuclear Information System (INIS)

1999-01-01

This Reference Design Description explains the current design for a potential geologic repository that may be located at Yucca Mountain in Nevada. It describes the proposed design for a surface facility, subsurface repository, and waste packaging; it also presents the current design of the key engineering systems for the final four phases: operations, monitoring, closure, and postclosure. In addition, this Reference Design Description reviews the expected long-term performance of the potential repository. In accordance with current law, this design does not include an interim storage option. This document has six major sections. Section 1 describes the physical layout of the proposed repository. The second section describes the 4-phase evolution of the development of the proposed repository. Section 3 describes the reception of waste from offsite locations. The fourth section details the various systems that will package the waste and move it below ground as well as safety monitoring and closure. Section 5 describes the systems (both physical and analytical) that ensure continued safety after closure. The final section offers design options that may be adopted to increase the margin of safety

Environmental effects on corrosion in the Tuff repository

International Nuclear Information System (INIS)

Beavers, J.A.; Thompson, N.G.

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

Future extension of the Swedish repository for low and intermediate level waste (SFR)

International Nuclear Information System (INIS)

Carlsson, Jan

2006-01-01

The existing Swedish repository for low and intermediate level waste (SFR) is licensed for disposal of short-lived waste originated from operation and maintenance of Swedish nuclear power plants. The repository is foreseen to be extended to accommodate short-lived waste from the future decommissioning of the Nuclear Power Plants. Long-lived waste from operation, maintenance and eventually decommissioning will be stored some years before disposal in a geological repository. This repository can be build either as a further extension of the SFR facility or as a separate repository. This paper discusses the strategy of a step-wise extended repository where the extensions are performed during operation of the existing parts of the repository. It describes the process for licensing new parts of the repository (and re-license of the existing parts). (author)

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)....

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

Study of nuclear waste storage capacity at Yucca mountain repository

International Nuclear Information System (INIS)

Zhou Wei; Apted, M.; Kessler, J.H.

2008-01-01

The Yucca Mountain repository is applying license for storing 70000 MTHM nuclear waste including commercial spent nuclear fuel (CSNF) and defense high-level radioactive waste (HLW). The 70000 MTHM is a legal not the technical limit. To study the technical limit, the Electric Power Research Institute (EPRI) carried out a systematic study to explore the potential impact if the repository will accept more waste. This paper describes the model and results for evaluating the spent-fuel disposal capacity for a repository at Yucca Mountain from the thermal and hydrological point of view. Two proposed alternative repository designs are analyzed, both of which would fit into the currently well-characterized site and, therefore, not necessitating any additional site characterization at Yucca Mountain. The two- and three-dimensional models for coupled thermo-hydrological analysis extends from the surface to the water table, covering all the major and subgroup rock layers of the planned repository, as well as formations above and below the repository horizon. A dual-porosity and dual-permeability approach is used to model coupled heat and mass transfer through fracture formations. The waste package heating and ventilation are all assumed to follow those of the current design. The results show that the repository is able to accommodate three times the amount of spent fuel compared to the current design, without extra spatial expansion or exceeding current thermal and hydrological constraints. (authors)

Chemopreventive effects of free and bound phenolics associated to steep waters (nejayote) obtained after nixtamalization of different maize types.

Science.gov (United States)

Rojas-García, Carlos; García-Lara, Silverio; Serna-Saldivar, Sergio O; Gutiérrez-Uribe, Janet A

2012-03-01

Free and bound phenolics extracts from nejayote solids were obtained after optimally lime-cooking blue, normal white, red, normal yellow, high-carotenoid and quality protein maize types. The extraction yield ranged from 4.47 to 10.05%. Bound phenolics extracts had higher content of total phenolics, antioxidant activity and ferulic acid compared to the free phenolics extracts. In general, free phenolics extracts were less cytotoxic than the bound phenolics counterparts. Bound phenolics extracts had higher induction of quinone reductase (QR) and particularly the normal yellow nejayote exerted the highest chemopreventive index tested in Hepa1c1c7 cells. When tested for monofunctional phase 2 induction capacity in BPrc1 cells, the bound phenolics extracts of blue, normal white and quality protein nejayotes were better inducers than the normal yellow counterpart. Particularly, the free phenolics extract of the white maize nejayote induced BPrc1 cells QR and exerted a higher chemopreventive index compared to the bound phenolics extract. Therefore, the nejayote of the normal white maize was the best source of monofunctional phase 2 enzyme inducers.

Interoperability Across the Stewardship Spectrum in the DataONE Repository Federation

Science.gov (United States)

Jones, M. B.; Vieglais, D.; Wilson, B. E.

2016-12-01

Thousands of earth and environmental science repositories serve many researchers and communities, each with their own community and legal mandates, sustainability models, and historical infrastructure. These repositories span the stewardship spectrum from highly curated collections that employ large numbers of staff members to review and improve data, to small, minimal budget repositories that accept data caveat emptor and where all responsibility for quality lies with the submitter. Each repository fills a niche, providing services that meet the stewardship tradeoffs of one or more communities. We have reviewed these stewardship tradeoffs for several DataONE member repositories ranging from minimally (KNB) to highly curated (Arctic Data Center), as well as general purpose (Dryad) to highly discipline or project specific (NEON). The rationale behind different levels of stewardship reflect resolution of these tradeoffs. Some repositories aim to encourage extensive uptake by keeping processes simple and minimizing the amount of information collected, but this limits the long-term utility of the data and the search, discovery, and integration systems that are possible. Other repositories require extensive metadata input, review, and assessment, allowing for excellent preservation, discovery, and integration but at the cost of significant time for submitters and expense for curatorial staff. DataONE recognizes these different levels of curation, and attempts to embrace them to create a federation that is useful across the stewardship spectrum. DataONE provides a tiered model for repositories with growing utility of DataONE services at higher tiers of curation. The lowest tier supports read-only access to data and requires little more than title and contact metadata. Repositories can gradually phase in support for higher levels of metadata and services as needed. These tiered capabilities are possible through flexible support for multiple metadata standards and services

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

Science.gov (United States)

Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

2017-07-01

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Repository emplacement costs for Al-clad high enriched uranium spent fuel

International Nuclear Information System (INIS)

McDonell, W.R.; Parks, P.B.

1994-01-01

A range of strategies for treatment and packaging of Al-clad high-enriched uranium (HEU) spent fuels to prevent or delay the onset of criticality in a geologic repository was evaluated in terms of the number of canisters produced and associated repository costs incurred. The results indicated that strategies in which neutron poisons were added to consolidated forms of the U-Al alloy fuel generally produced the lowest number of canisters and associated repository costs. Chemical processing whereby the HEU was removed from the waste form was also a low cost option. The repository costs generally increased for isotopic dilution strategies, because of the substantial depleted uranium added. Chemical dissolution strategies without HEU removal were also penalized because of the inert constituents in the final waste glass form. Avoiding repository criticality by limiting the fissile mass content of each canister incurred the highest repository costs

Prestudy Oskarshamn. Tourism in Oskarshamn with or without a repository

International Nuclear Information System (INIS)

Nordblom, C.J.; Foghagen, C.

1998-11-01

Consequences for the tourism at Oskarshamn from siting a spent fuel repository in the community are studied. Four questionnaire/interview enquires were performed, and the analysis of the results show that no noticeable effects are expected. Still, an uncertainty about the impact of a repository is felt by the public, and more thorough information about the repository and its components is needed

Establishing managerial requirements for low-and intermediate-level waste repository

International Nuclear Information System (INIS)

Chung, C. W.; Lee, Y. K.; Kim, H. T.; Park, W. J.; Suk, T. W.; Park, S. H.

2004-01-01

This paper reviews basic considerations for establishing managerial requirements on the domestic low-and intermediate-level radioactive waste repository and presents the corresponding draft requirements. The draft emphasizes their close linking with the related regulations, standards and safety assessment for the repository. It also proposes a desirable direction towards harmonizing together with the existing waste acceptance requirements for the repository

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.

Radionuclide getters in the near-field chemistry of repositories

International Nuclear Information System (INIS)

Holland, T.R.; Lee, D.J.

1993-01-01

The ultimate release of radionuclides from a radioactive waste repository will depend upon the natural and man-made barriers surrounding the site. An opportunity exists to enhance natural radionuclide retention through improved sorption, by the use of suitable additives applied to the repository backfill material. This programme of work was designed to identify problem isotopes, to search for suitable materials to enhance their retention and ultimately to provide, through experimental studies, an understanding of their effectiveness under repository conditions. (Author)

Achieving public acceptance. Lessons from national repository programs

International Nuclear Information System (INIS)

Isaacs, Tom

2008-01-01

Essentially all countries pursuing nuclear waste repository programs have had long and dynamic histories. There have had changes in policies, programs, and national laws, many successes and more failures. Most continue to pursue the siting and development of geologic repositories for the ultimate disposal of the spent nuclear fuel (or reprocessed wastes) arising from the operation of nuclear power plants. And while many have had very strong repository science and technology programs, they have continued to find significant challenges associated with the societal acceptance issues required for such programs to be successful. Over recent years repository programs have developed and implemented rather different approaches to managing the non-technical (e.g. societal, political, and institutional) aspects of repository program development. This is not unexpected as programs have had different histories, operate under different laws, reside in countries with different cultures and values, and are managed under different formulations. For example, the U.S. program is implemented by a branch of the Department of Energy while in several other countries the program is managed by a separate corporation on behalf of the nuclear waste owners or dedicated quasi-governmental organizations. These similar, but different programs, and their rich histories and current work, provide an excellent opportunity to investigate features that have and have not proven successful in helping to achieve public acceptance. This paper will review some of the compelling aspects and provide some guidelines for applications in other national circumstances. Recent experiences will be evaluated to discern emerging trends for achieving public acceptance in nuclear repository development and in the broader dimensions associated with the potential renaissance of nuclear power. (author)

Impact of transporting defense high-level waste to a geologic repository

International Nuclear Information System (INIS)

Joy, D.S.; Shappert, L.B.; Boyle, J.W.

1984-12-01

The Nuclear Waste Policy Act of 1982 (Public Law 97-425) provides for the development of repositories for the disposal of high-level radioactive waste and spent nuclear fuel and requires the Secretary of Energy to evaluate five potential repository sites. One factor that is to be examined is transportation of radioactive materials to such a repository and whether transportation might be affected by shipments to a defense-only repository, or to one that accepts both defense and commercial waste. In response to this requirement, The Department of Energy has undertaken an evaluation of the cost and risk associated with the potential shipments. Two waste-flow scenarios are considered which are related to the total quantity of defense high-level waste which will be placed in a repository. The low-flow case is based on a total of 6700 canisters being transported from one site, while the high-flow case assumes that a total of 20,000 canisters will be transported from three sites. For the scenarios considered, the estimated shipping costs range from $105 million to $257 million depending upon the mode of transport and the repository location. The total risks associated with shipping defense high-level waste to a repository are estimated to be significantly smaller than predicted for other transportation activities. In addition, the cost of shipping defense high-level waste to a repository does not depend on whether the site is a defense-only or a commercial repository. Therefore, the transportation considerations are not a basis for the selection of one of the two disposal options

Estimating the economic impact of a repository from scenario-based surveys: Models of the relation of stated intent to actual behavior

International Nuclear Information System (INIS)

Easterling, D.; Morwitz, V.; Kunreuther, H.

1990-12-01

The task of estimating the economic impact of a facility as novel and long-lived as a high-level nuclear waste (HLNW) repository is fraught with uncertainty. One approach to the forecasting problems is to survey economic agents as to how they would respond when confronted with hypothetical repository scenarios. A series of such studies conducted for the state of Nevada have examined the potential impact of a Yucca Mountain repository on behavior such as planning conventions, attending conventions, vacationing, outmigration, immigration, and business location. In each case, respondents drawn from a target population report on whether a particular repository event (either some form of an accident, or simply the presence of the facility) would cause them to act any differently than they otherwise would. The responses to such a survey provide an indication of whether or not economic behavior would be altered. However, the analysis is inevitably plagued with the question of how much credence to place in the reports of intended behavior; can we believe what people report they would do in a hypothetical situation? The present study examines a more precise version of this question regarding the validity of stated intent data. After reviewing a variety of literature in the area of intent versus actual behavior, we provide an answer to the question, ''What levels of actual behavior are consistent with the intent data that have been observed in the repository surveys?'' More formally, we assume that we are generally interested in predicting the proportion of a sample who will actually perform a target behavior. 86 refs., 6 figs., 9 tabs

Durability of cemented waste in repository and under simulated conditions

International Nuclear Information System (INIS)

Dragolici, F.; Nicu, M.; Lungu, L.; Turcanu, C.; Rotarescu, Gh.

2000-01-01

simulated disposal conditions for reference samples; - emplacement of reference samples in Baita Bihor Repository for real disposal characterization. All samples were positioned in five locations of Baita-Bihor repository where they will be kept for 1, 3, 5 and 10 years before mechanical and structural characterization. These locations have different humidity values, decreasing from location 1 to 5. The results will be compared with those obtained for the same type of samples kept in laboratory conditions. The mechanical performances of the matrix with cement-mineral additives are not influenced if bentonite or volcanic tuff concentration is is lower than 10%. The very good mechanical behaviour of the samples, drives at the conclusion that the additive cement-mineral mixture could be used in the disposal procedure, with good results, if the future structure characterization would prove the role as engineered barrier. Complexing reagents reduce drastically the mechanical performances. The chemical nature of the complexing agent plays an important role, the damaging effect being more pregnant for tartaric and citric acid than for oxalic acid. In any case there is a maximum limit of concentration which is acceptable from mechanical point of view. The mechanical resistance observed in all samples, after one year disposal, are within the accepted limits for the matrix durability. Thus, disposal conditions has not influence the mechanical properties of the cement matrix after one year disposal. The presented results, showed that bentonite seems to have a positive influence on the quality of the examined matrices . These results are preliminary. The data obtained so far will be completed with those to be obtained after three year disposal. XRD initial investigation of waste samples showed complex changes in the structure and components. To understand the systems, series of different compositions need to be characterized. In the next years the durability of samples kept for times

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.

[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.

Polyethylene Glycol Mediated Colorectal Cancer Chemoprevention: Roles of Epidermal Growth Factor Receptor and Snail

Science.gov (United States)

Wali, Ramesh K.; Kunte, Dhananjay P.; Koetsier, Jennifer L.; Bissonnette, Marc; Roy, Hemant K.

2008-01-01

Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We previously reported that Snail/β-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overepressed in ~80% of human colorectal cancers (CRC), on PEG-mediated anti-proliferative and hence anti-neoplastic effects in azoxymethane (AOM)-rats and HT-29 colon cancer cells. AOM-rats were randomized to either standard diet or one with 10% PEG 3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (pPEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pre-treating cells with gefitinib or stably transfecting with EGFR-shRNA and measured the effect of PEG on proliferation. In either case PEG effect was blunted suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-shRNA cells, besides having reduced membrane EGFR also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/β-catenin pathway playing the central intermediary function. PMID:18790788

Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail.

Science.gov (United States)

Wali, Ramesh K; Kunte, Dhananjay P; Koetsier, Jennifer L; Bissonnette, Marc; Roy, Hemant K

2008-09-01

Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We reported previously that Snail/beta-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overexpressed in approximately 80% of human colorectal cancers, on PEG-mediated antiproliferative and hence antineoplastic effects in azoxymethane (AOM) rats and HT-29 colon cancer cells. AOM rats were randomized to either standard diet or one with 10% PEG-3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (P PEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pretreating cells with gefitinib or stably transfecting with EGFR-short hairpin RNA and measured the effect of PEG on proliferation. In either case, PEG effect was blunted, suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-short hairpin RNA cells, besides having reduced membrane EGFR, also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells, PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/beta-catenin pathway playing the central intermediary function.

Identifying Tensions in the Use of Open Licenses in OER Repositories

Science.gov (United States)

Amiel, Tel; Soares, Tiago Chagas

2016-01-01

We present an analysis of 50 repositories for educational content conducted through an "audit system" that helped us classify these repositories, their software systems, promoters, and how they communicated their licensing practices. We randomly accessed five resources from each repository to investigate the alignment of licensing…

Development of an object-oriented simulation code for repository performance assessment

International Nuclear Information System (INIS)

Tsujimoto, Keiichi; Ahn, J.

1999-01-01

As understanding for mechanisms of radioactivity confinement by a deep geologic repository improves at the individual process level, it has become imperative to evaluate consequences of individual processes to the performance of the whole repository system. For this goal, the authors have developed a model for radionuclide transport in, and release from, the repository region by incorporating multiple-member decay chains and multiple waste canisters. A computer code has been developed with C++, an object-oriented language. By utilizing the feature that a geologic repository consists of thousands of objects of the same kind, such as the waste canister, the repository region is divided into multiple compartments and objects for simulation of radionuclide transport. Massive computational tasks are distributed over, and executed by, multiple networked workstations, with the help of parallel virtual machine (PVM) technology. Temporal change of the mass distribution of 28 radionuclides in the repository region for the time period of 100 million yr has been successfully obtained by the code

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...

University digital repositories and authors.

Directory of Open Access Journals (Sweden)

Alice Keefer

2008-02-01

Full Text Available The Open Access movement offers two strategies for making scientific information available without economic, technical or legal obstacles: the publication of articles in OA journals and the deposit by authors of their Works in stable institutional or discipline-based repositories. This article explores the implementation of the second “route” on the part of authors, because it is the strategy that offers the greatest possibility of attaining OA in the short term. However, it does require repositories to exert great effort in informing the authors of the advantages of self-archiving and of the procedures for depositing their work and, even helping them to do so – through services and promotional activities.

Construction of quality-assured infant feeding process of care data repositories: Construction of the perinatal repository (Part 2).

Science.gov (United States)

García-de-León-Chocano, Ricardo; Muñoz-Soler, Verónica; Sáez, Carlos; García-de-León-González, Ricardo; García-Gómez, Juan M

2016-04-01

This is the second in a series of two papers regarding the construction of data quality (DQ) assured repositories, based on population data from Electronic Health Records (EHR), for the reuse of information on infant feeding from birth until the age of two. This second paper describes the application of the computational process of constructing the first quality-assured repository for the reuse of information on infant feeding in the perinatal period, with the aim of studying relevant questions from the Baby Friendly Hospital Initiative (BFHI) and monitoring its deployment in our hospital. The construction of the repository was carried out using 13 semi-automated procedures to assess, recover or discard clinical data. The initial information consisted of perinatal forms from EHR related to 2048 births (Facts of Study, FoS) between 2009 and 2011, with a total of 433,308 observations of 223 variables. DQ was measured before and after the procedures using metrics related to eight quality dimensions: predictive value, correctness, duplication, consistency, completeness, contextualization, temporal-stability, and spatial-stability. Once the predictive variables were selected and DQ was assured, the final repository consisted of 1925 births, 107,529 observations and 73 quality-assured variables. The amount of discarded observations mainly corresponds to observations of non-predictive variables (52.90%) and the impact of the de-duplication process (20.58%) with respect to the total input data. Seven out of thirteen procedures achieved 100% of valid births, observations and variables. Moreover, 89% of births and ~98% of observations were consistent according to the experts׳ criteria. A multidisciplinary approach along with the quantification of DQ has allowed us to construct the first repository about infant feeding in the perinatal period based on EHR population data. Copyright © 2016 Elsevier Ltd. All rights reserved.

Siting regions for deep geological repositories. Why just here?

International Nuclear Information System (INIS)

Rieser, A.

2009-09-01

This report helps to the popularization of the Nagra works accomplished for the management and disposal of the radioactive wastes in Switzerland. The programme for management and disposal of the radioactive wastes are extensively determined by regulations. Protection of mankind and environment is the primary objective. The basic storage process is considered as having been solved. The question addressed in the report is where the facility has to be built; the site selection procedure includes five steps: 1) according to their type the wastes have to be allocated to two different repositories: for low- and intermediate-level wastes (L/ILW), and for high-level and alpha-toxic wastes (HLW); 2) the safety concept for both repositories and the requirements on the geology have to be determined; 3) large suitable geological-tectonic zones must be found where repositories could be built; 4) in these geological zones a suitable host rock has to be identified; 5) the most important spatial geological conditions of the host rock (minimum depth with respect to surface erosion, maximum depth in terms of engineering requirements, lateral extent) have to be identified. Based on these criteria, three suitable siting regions for a HLW repository were found in the North of Switzerland. The preferred host rock is Opalinus clay because of its very low permeability; it is therefore an excellent barrier against nuclide transport. In the three proposed siting regions, Opalinus clay is present in sufficient volumes at a suitable depth. For a L/ILW repository six different possible siting regions were identified, five in Northern Switzerland and one in Central Switzerland. In the three siting regions found for a possible HLW repository, it would also be possible to built a combined repository for both HLW and L/ILW wastes

Ground water movements around a repository. Rock mechanics analyses

International Nuclear Information System (INIS)

Ratigan, J.L.

1977-09-01

The determination and rational assessment of groundwater flow around a repository depends upon the accurate analysis of several interdependent and coupled phenomenological events occuring within the rock mass. In particular, the groundwater flow pathways (joints) are affected by the excavation and thermomechanical stresses developed within the rock mass, and the properties, of the groundwater are altered by the temperature perturbations in the rock mass. The objective of this report is to present the results of the rock mechanics analysis for the repository excavation and the thermally-induced loadings. Qualitative analysis of the significance of the rock mechanics results upon the groundwater flow is provided in this report whenever such an analysis can be performed. Non-linear rock mechanics calculations have been completed for the repository storage tunnels and the global repository domain. The rock mass has been assumed to possess orthoganol joint sets or planes of weakness with finite strength characteristics. In the local analyses of the repository storage tunnels the effects of jointorientation and repository ventilation have been examined. The local analyses indicated that storage room support requirements and regions of strength failure are highly dependent upon joint orientation. The addition of storage tunnel ventilation was noted to reduce regions of strength failure, particularly during the 30 year operational phase of the repository. Examination of the local stresses around the storage tunnels indicated the potential for perturbed hydraulic permeabilities. The permeabilities can be expected to be altered to a greater degree by the stresses resulting from excavation than from stresses which are thermally induced. The thermal loading provided by the instantaneous waste emplacement resulted in stress states and displacements quite similar to those provided by the linear waste emplacement sequence

Reference design description for a geologic repository: Revision 01

International Nuclear Information System (INIS)

1997-09-01

This document describes the current design expectations for a potential geologic repository that could be located at Yucca Mountain in Nevada. This Reference Design Description (RDD) looks at the surface and subsurface repository and disposal container design. Additionally, it reviews the expected long-term performance of the potential repository. In accordance with current legislation, the reference design for the potential repository does not include an interim storage option. The reference design presented allows the disposal of highly radioactive material received from government-owned spent fuel custodian sites; produces high-level waste sites, and commercial spent fuel sites. All design elements meet current federal, state, and local regulations governing the disposal of high-level radioactive waste and protection of the public and the environment. Due to the complex nature of developing a repository, the design will be created in three phases to support Viability Assessment, License Application, and construction. This document presents the current reference design. It will be updated periodically as the design progresses. Some of the details presented here may change significantly as more cost-effective solutions, technical advancements, or changes to requirements are identified

The Hidden Risk Decisions in Waste Repository Regulation

International Nuclear Information System (INIS)

Frishman, Steve

2001-01-01

The move toward risk-informed, performance-based regulation of activities involving radioactive materials is becoming wide spread and broadly applied. While this approach may have some merit in specific applications in which there is a considerable body of experience, its strict application in regulation of geologic repositories for highly radioactive wastes may not be appropriate for this unproven and socially controversial technology. The U.S. Nuclear Regulatory Commission describes risk-informed, performance-based regulation as 'an approach in which risk insights, engineering analysis and judgement (eg. defense in depth), and performance history are used to (1) focus attention on the most important activities, (2) establish objective criteria based upon risk insights for evaluating performance, (3) develop measurable or calculable parameters for monitoring system and licensee performance, and (4) focus on the results as the primary basis for regulatory decision-making.' Both the risk-informed and performance-based elements of the approach are problematic when considering regulation of geologic repositories for highly radioactive wastes - an activity yet to be accomplished by any nation. In investigating potential sites for geologic repositories there will always be residual uncertainty in understanding the natural system and the events and processes that affect it. The more complex the natural system, the greater will be the uncertainty in both the data and the models used to describe the characteristics of the site's natural barriers, and the events and processes that could affect repository waste isolation. The engineered barriers also are subject to uncertainties that are important to the repository system. These uncertainties translate themselves into a range of probabilities that certain events or processes, detrimental to waste isolation, will occur. The uncertainties also translate to a range of consequences and magnitudes of consequences, should the

Instrument reliability for high-level nuclear-waste-repository applications

International Nuclear Information System (INIS)

Rogue, F.; Binnall, E.P.; Armantrout, G.A.

1983-01-01

Reliable instrumentation will be needed to evaluate the characteristics of proposed high-level nuclear-wasted-repository sites and to monitor the performance of selected sites during the operational period and into repository closure. A study has been done to assess the reliability of instruments used in Department of Energy (DOE) waste repository related experiments and in other similar geological applications. The study included experiences with geotechnical, hydrological, geochemical, environmental, and radiological instrumentation and associated data acquisition equipment. Though this paper includes some findings on the reliability of instruments in each of these categories, the emphasis is on experiences with geotechnical instrumentation in hostile repository-type environments. We review the failure modes, rates, and mechanisms, along with manufacturers modifications and design changes to enhance and improve instrument performance; and include recommendations on areas where further improvements are needed

Environmental assessment overview, Reference repository location, Hanford site, Washington

International Nuclear Information System (INIS)

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. On the basis of the evaluations reported in this EA, the DOE has found that the Hanford site is not disqualified under the guidelines. On the basis of these findings, the DOE is nominating the Hanford site as one of five sites suitable for characterization. 3 figs

An open repositories network development for medical teaching resources.

Science.gov (United States)

Soula, Gérard; Darmoni, Stefan; Le Beux, Pierre; Renard, Jean-Marie; Dahamna, Badisse; Fieschi, Marius

2010-01-01

The lack of interoperability between repositories of heterogeneous and geographically widespread data is an obstacle to the diffusion, sharing and reutilization of those data. We present the development of an open repositories network taking into account both the syntactic and semantic interoperability of the different repositories and based on international standards in this field. The network is used by the medical community in France for the diffusion and sharing of digital teaching resources. The syntactic interoperability of the repositories is managed using the OAI-PMH protocol for the exchange of metadata describing the resources. Semantic interoperability is based, on one hand, on the LOM standard for the description of resources and on MESH for the indexing of the latter and, on the other hand, on semantic interoperability management designed to optimize compliance with standards and the quality of the metadata.

ArrayWiki: an enabling technology for sharing public microarray data repositories and meta-analyses

Science.gov (United States)

Stokes, Todd H; Torrance, JT; Li, Henry; Wang, May D

2008-01-01

Background A survey of microarray databases reveals that most of the repository contents and data models are heterogeneous (i.e., data obtained from different chip manufacturers), and that the repositories provide only basic biological keywords linking to PubMed. As a result, it is difficult to find datasets using research context or analysis parameters information beyond a few keywords. For example, to reduce the "curse-of-dimension" problem in microarray analysis, the number of samples is often increased by merging array data from different datasets. Knowing chip data parameters such as pre-processing steps (e.g., normalization, artefact removal, etc), and knowing any previous biological validation of the dataset is essential due to the heterogeneity of the data. However, most of the microarray repositories do not have meta-data information in the first place, and do not have a a mechanism to add or insert this information. Thus, there is a critical need to create "intelligent" microarray repositories that (1) enable update of meta-data with the raw array data, and (2) provide standardized archiving protocols to minimize bias from the raw data sources. Results To address the problems discussed, we have developed a community maintained system called ArrayWiki that unites disparate meta-data of microarray meta-experiments from multiple primary sources with four key features. First, ArrayWiki provides a user-friendly knowledge management interface in addition to a programmable interface using standards developed by Wikipedia. Second, ArrayWiki includes automated quality control processes (caCORRECT) and novel visualization methods (BioPNG, Gel Plots), which provide extra information about data quality unavailable in other microarray repositories. Third, it provides a user-curation capability through the familiar Wiki interface. Fourth, ArrayWiki provides users with simple text-based searches across all experiment meta-data, and exposes data to search engine crawlers

Planning the rad waste repository - Croatian case

International Nuclear Information System (INIS)

Kucar Dragicevic, S.; Subasic, D.; Lokner, V.

1996-01-01

Radioactive waste is generated in Croatia from various nuclear applications as well as from the Krsko NPP (Slovenian and Croatian joint venture facility). The national programme on radioactive waste management is aimed at straightening existing infrastructure, establishing new (more transparent) system of responsibilities and development of new legislation. The siting of LL/ILW repository is important segments of the whole radioactive waste management cycle. The status and efficiency of the rad waste management infrastructure in the country have the significant influence on all the activities related to the project of repository construction - from the very first phases of preliminary planning and background preparations to advanced phases of the project development. The present status of the Croatian national radioactive waste infrastructure and its influence on the repository project are presented. The role of national legislation and institutional framework are specially discussed. (author)

Modelling gas generation in radioactive waste repositories

International Nuclear Information System (INIS)

Agg, P.J.

1993-02-01

In a repository containing low- and intermediate-level waste, gas generation will occur principally by the coupled processes of metal corrosion and microbial degradation of cellulosic waste. This Paper describes a mathematical model design to address gas generation by these mechanisms. The metal corrosion model incorporates a three-stage process encompassing both aerobic and anaerobic corrosion regimes; the microbial degradation model simulates the activities of eight different microbial populations, which are maintained as functions both of pH and of the concentrations of particular chemical species. Gas concentrations have been measured over a period of three years in large-scale drum experiments designed to simulate repository conditions. Model predictions are confirmed against the experimental measurements, and a prediction is then made of gas concentrations and generation rates over an assessment period of one million years in a radioactive waste repository. (author)

Modelling gas generation in radioactive waste repositories

International Nuclear Information System (INIS)

Agg, P.J.

1992-07-01

In a repository containing low- and intermediate-level waste, gas generation will occur principally by the coupled processes of metal corrosion and microbial degradation of cellulosic waste. This paper describes a mathematical model designed to address gas generation by these mechanisms. The metal corrosion model incorporates a three-stage process encompassing both aerobic and anaerobic corrosion regimes; the microbial degradation model simulates the activities of eight different microbial populations, which are maintained as functions both of pH and of the concentrations of particular chemical species. Gas concentrations have been measured over a period of three years in large-scale drum experiments designed to simulate repository conditions. Model predictions are confirmed against the experimental measurements, and a prediction is then made of gas concentrations and generation rates over an assessment period of one million years in a radioactive waste repository. (Author)

Analysis of the seismic hazard to an underground waste repository

International Nuclear Information System (INIS)

Wight, L.H.

1979-01-01

Conclusions are: The consequence associated with intense vibratory shaking of a well-designed repository is essentially negligible. The specification of an appropriate seismic vibratory design criteria could best be accomplished with a Bayesian seismic hazard assessment, using geologic slip rates as input. The consequence associated with fault displacement is very site specific and dependent on the host geologic media and its permeability changes in response to fault displacement. The probability of faulting through a repository in its million year design life is rather high, principally because of a high probability of primary or secondary faulting on undetected faults. The faulting probability can be minimized by deploying sophisticated site certification programs. High resolution microseismic surveillance seems to be most appropriate. The author's judgement is that the repository simulation program can neglect consequences associated with shaking of the repository, but that the probability of significant fault displacement through the repository during its design life should be conservatively taken as one

Developing of Radioactive Wastes Management Safety at Baldone Repository Radons

International Nuclear Information System (INIS)

Abramenkovs, A.; Abramenkova, G.; Klavins, M.

2008-01-01

The near surface radioactive wastes repository Radons near the Baldone city was put in operation in 1962. The safety assessment of repository was performed during 2000-2001 under the PHARE project to evaluate the recommended upgrades of repository. The outline design for new vaults and interim storage for long lived radioactive wastes was elaborated during 2003-2004 years. The Environmental Impact Assessment (EIA) for upgrade of Baldone repository was performed during 2004-2005 years. Additional evaluations of radioactive wastes management safety were performed during 2006 year by the experts of ENRESA, Spain. It was shown, that the additional efforts were spent for improving of radioactive wastes cementation in concrete containers. The results of tritium and Cs 137 leaching studies are presented and discussed. It was shown, that additives can significantly reduce the migration of radionuclides in ground water. The leaching coefficients for tritium and Cs 137 were determined to supply with the necessary data the risk assessment calculations for operation of Baldone repository R adons

Understanding large scale groundwater flow to aid in repository siting

International Nuclear Information System (INIS)

Davison, C.C.; Brown, A.; Gascoyne, M.; Stevenson, D.R.; Ophori, D.U.

1996-01-01

Atomic Energy of Canada Limited (AECL) with support from Ontario Hydro has developed a concept for the safe disposal of Canada's nuclear fuel waste in a deep (500 to 1000 m) mined repository in plutonic rocks of the Canadian Shield. The disposal concept involves the use of multiple engineered and natural barriers to ensure long-term safety. The geosphere, comprised of the enclosing rock mass and the groundwater which occurs in cracks and pores in the rock, is expected to serve as an important natural barrier to the release and migration of wastes from the engineered repository. Although knowledge of the physical and chemical characteristics of the groundwater in the rock at potential repository sites is needed to help design the engineered barriers of the repository it can also be used to aid in repository siting, to take greater advantage of natural conditions in the geosphere to enhance its role as a barrier in the overall disposal system

Nuclear waste repository in basalt: preconceptual design guidelines

International Nuclear Information System (INIS)

1979-06-01

The development of the basalt waste isolation program parallels the growing need for permanent, environmentally safe, and secure means to store nuclear wastes. The repository will be located within the Columbia Plateau basalt formations where these ends can be met and radiological waste can be stored. These wastes will be stored such that the wastes may be retrieved from storage for a period after placement. After the retrieval period, the storage locations will be prepared for terminal storage. The terminal storage requirements will include decommissioning provisions. The facility boundaries will encompass no more than several square miles of land which will be above a subsurface area where the geologic makeup is primarily deep basaltic rock. The repository will receive, from an encapsulation site(s), nuclear waste in the form of canisters (not more than 18.5 feet x 16 inches in diameter) and containers (55-gallon drums). Canisters will contain spent fuel (after an interim 5-year storage period), solidified high-level wastes (HLW), or intermediate-level wastes (ILW). The containers (drums) will package the low-level transuranic wastes (LL-TRU). The storage capacity of the repository will be expanded in a time-phased program which will require that subsurface development (repository expansion) be conducted concurrently with waste storage operations. The repository will be designed to store the nuclear waste generated within the predictable future and to allow for reasonable expansion. The development and assurance of safe waste isolation is of paramount importance. All activities will be dedicated to the protection of public health and the environment. The repository will be licensed by the US Nuclear Regulatory Commission (NRC). Extensive efforts will be made to assure selection of a suitable site which will provide adequate isolation

Public concerns and choices regarding nuclear-waste repositories

International Nuclear Information System (INIS)

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

Nuclear waste repository in basalt: preconceptual design guidelines

Energy Technology Data Exchange (ETDEWEB)

1979-06-01

The development of the basalt waste isolation program parallels the growing need for permanent, environmentally safe, and secure means to store nuclear wastes. The repository will be located within the Columbia Plateau basalt formations where these ends can be met and radiological waste can be stored. These wastes will be stored such that the wastes may be retrieved from storage for a period after placement. After the retrieval period, the storage locations will be prepared for terminal storage. The terminal storage requirements will include decommissioning provisions. The facility boundaries will encompass no more than several square miles of land which will be above a subsurface area where the geologic makeup is primarily deep basaltic rock. The repository will receive, from an encapsulation site(s), nuclear waste in the form of canisters (not more than 18.5 feet x 16 inches in diameter) and containers (55-gallon drums). Canisters will contain spent fuel (after an interim 5-year storage period), solidified high-level wastes (HLW), or intermediate-level wastes (ILW). The containers (drums) will package the low-level transuranic wastes (LL-TRU). The storage capacity of the repository will be expanded in a time-phased program which will require that subsurface development (repository expansion) be conducted concurrently with waste storage operations. The repository will be designed to store the nuclear waste generated within the predictable future and to allow for reasonable expansion. The development and assurance of safe waste isolation is of paramount importance. All activities will be dedicated to the protection of public health and the environment. The repository will be licensed by the US Nuclear Regulatory Commission (NRC). Extensive efforts will be made to assure selection of a suitable site which will provide adequate isolation.

Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

Science.gov (United States)

Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

2017-05-03

Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

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.

Report of the Task Force on the MRS/repository interface

International Nuclear Information System (INIS)

1986-02-01

In April 1985, the DOE established an MRS/repository interface task force to analyze the cost and schedule impacts of implementing an integrated waste-management system on the repository and the MRS facility. The intended end products of the study were preliminary conceptual designs of repository and MRS facilities, cost and schedule estimates, and other analyses that would advance the definition of the role and function of the MRS facility, support the preparation of the MRS proposal to Congress, and serve as a source of baseline data for further studies of the integrated waste-management system. From the general overall objectives, specific equations were developed to guide the task-force effort, e.g., What would the surface facilities at the repository look like and cost with an MRS facility in the system. In order to address these questions, five scenarios were defined and analyzed. (A number of other scenarios and associated issues were also explored to a lesser extent.) These five scenarios are as follows. Scenario 1: reference case (no MRS facility). Scenario 2: MRS facility with overpacking of both spent fuel and defense high-level waste. Scenario 3: MRS facility with overpacking of spent fuel only (defense-waste overpacking at the repository). Scenario 4: MRS facility with all overpacking at the repository. Scenario 5: MRS facility with all overpacking at the repository and western fuel shipped directly to the repository. It is apparent that, with such a limited set of scenarios, determination of the optimum system was not an objective of this study. Furthermore, time constraints limited the level of detail to which facility designs could be developed; this level can best be characterized as ''preconceptual.'' These limitations are, however, compatible with the intent of the study, which was to make general comparisons between the several systems on an internally consistent basis

Chemical conditions in the repository for low- and intermediate-level reactor waste

International Nuclear Information System (INIS)

Snellman, M.; Uotila, H.

1984-01-01

The chemical conditions in the proposed repositories for low- and intermediate-level reactor waste at Haestholmen (IVO) and Olkiluoto (TVO) have been discussed with respect to materials introduced into the repository, their possible long-term changes and interaction with groundwater flowing into the repository. The main possible groundwater-rock interactions have been discussed, as well as the role of micro-organisms, organic acids and colloids in the estimation of the barrier integrity. Experimental and theoretical studies have been performed on the basis of the natural groundwater compositions expected at the repository sites. Main emphasis is put on the chemical parameters which might influence the integrity of the different barriers in the repository as well as on the parameters which might effect the release and transport of radionuclides from the repository

An approach to improve Romanian geological repository planning

International Nuclear Information System (INIS)

Andrei, Veronica; Prisecaru, Ilie

2016-01-01

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

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

International Nuclear Information System (INIS)

Savage, D.; Stenhouse, M.; Benbow, S.

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 -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 -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 have been

Radioactive waste disposal: Recommendations for a repository site selection

International Nuclear Information System (INIS)

Cadelli, N.; Orlowski, S.

1992-01-01

This report is a guidebook on recommendations for site selection of radioactive waste repository, based on a consensus in european community. This report describes particularly selection criteria and recommendations for radioactive waste disposal in underground or ground repositories. 14 refs

Data vaults: a database welcome to scientific file repositories

NARCIS (Netherlands)

Ivanova, M.; Kargın, Y.; Kersten, M.; Manegold, S.; Zhang, Y.; Datcu, M.; Espinoza Molina, D.

2013-01-01

Efficient management and exploration of high-volume scientific file repositories have become pivotal for advancement in science. We propose to demonstrate the Data Vault, an extension of the database system architecture that transparently opens scientific file repositories for efficient in-database

Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells.

Science.gov (United States)

Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Uckoo, Ram M; Patil, Bhimanagouda S

2012-02-01

Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833μg/mL in 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, Pwater (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF-7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thermal Analysis of a Nuclear Waste Repository in Argillite Host Rock

Science.gov (United States)

Hadgu, T.; Gomez, S. P.; Matteo, E. N.

2017-12-01

Disposal of high-level nuclear waste in a geological repository requires analysis of heat distribution as a result of decay heat. Such an analysis supports design of repository layout to define repository footprint as well as provide information of importance to overall design. The analysis is also used in the study of potential migration of radionuclides to the accessible environment. In this study, thermal analysis for high-level waste and spent nuclear fuel in a generic repository in argillite host rock is presented. The thermal analysis utilized both semi-analytical and numerical modeling in the near field of a repository. The semi-analytical method looks at heat transport by conduction in the repository and surroundings. The results of the simulation method are temperature histories at selected radial distances from the waste package. A 3-D thermal-hydrologic numerical model was also conducted to study fluid and heat distribution in the near field. The thermal analysis assumed a generic geological repository at 500 m depth. For the semi-analytical method, a backfilled closed repository was assumed with basic design and material properties. For the thermal-hydrologic numerical method, a repository layout with disposal in horizontal boreholes was assumed. The 3-D modeling domain covers a limited portion of the repository footprint to enable a detailed thermal analysis. A highly refined unstructured mesh was used with increased discretization near heat sources and at intersections of different materials. All simulations considered different parameter values for properties of components of the engineered barrier system (i.e. buffer, disturbed rock zone and the host rock), and different surface storage times. Results of the different modeling cases are presented and include temperature and fluid flow profiles in the near field at different simulation times. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and

From the repository to the deep geological repository - and back to the Terrain surface?

International Nuclear Information System (INIS)

Lahodynsky, R.

2011-01-01

How deep is 'safe'? How long is long-term? How and for how long will something be isolated? Which rock, which formation and which location are suitable? A repository constructed for the safekeeping of radioactive or highly toxic wastes can be erected either on the surface, near the surface or underground. Radioactive waste is currently often stored at near-surface locations. The storage usually takes place nearby of a nuclear power plant in pits or concrete tombs (vaults). However, repositories can also be found in restricted areas, e.g. near nuclear weapon production or reprocessing plants (WAA) or nuclear weapons test sites (including Tomsk, Russia, Hanford and Nevada desert, USA), or in extremely low rainfall regions (South Africa). In addition there are disused mines which are now used as underground repositories. Low-level and medium-active (SMA) but also high-level waste (HAA) are stored at these types of sites (NPP, WAA, test areas, former mines). In Russia (Tomsk, Siberia) liquid radioactive waste has been injected into deep geological formations for some time (Minatom, 2001). However, all these locations are not the result of a systematic, scientific search or a holistic process for finding a location, but the result of political decisions, sometimes ignoring scientific findings. Why underground storage is given preference over high-security landfill sites (HSD) often has economic reasons. While a low safety standard can significantly reduce the cost of an above-ground high-security landfill as a waste disposal depot, spending remains high, especially due to the need for capital formation to cover operating expenses after filling the HSD. In the case of underground storage, on the other hand, no additional expenses are required for the period after backfilling. The assumption of lower costs for a deep repository runs through the past decades and coincides with the assumption that the desired ideal underground conditions actually exist and will

Region-to-area screening methodology for the crystalline repository project

International Nuclear Information System (INIS)

1984-08-01

The ''Nuclear Waste Policy Act of 1982'' (NWPA), enacted January 7, 1983 as Public Law 97-425, confirmed the responsibility of the US Department of Energy (DOE) for management of high-level radioactive waste. The NWPA directed the DOE to provide safe facilities for isolation of high-level radioactive waste from the environment in federally owned and federally licensed repositories. To achieve the goals of providing licensed repositories for high-level radioactive waste, a technical program has been developed by the DOE to meet all relevant radiological protection criteria and other requirements. By March 1987, the NWPA requires the DOE to recommend to the President a single site, chosen from five nominated sites for construction of the first repository. Rock types being considered as potential hosts for the first repository include salt, basalt, and tuff. The NWPA also requires the DOE to select three candidate sites, chosen from five nominated sites to be recommended to the President by July 1989, as possible locations for the second repository. Potential host rock types for the second federal repository will include crystalline rock. This document outlines the methodology for region-to-area screening of exposed crystalline rock bodies for suitability as sites for further study. 17 refs., 14 figs., 2 tabs

Acceptability of a low and intermediate level radioactive waste repository

International Nuclear Information System (INIS)

Zeleznik, N.; Polic, M.

2000-01-01

Siting of a radioactive waste repository, even for the waste of low and intermediate level (LILW) radioactivity, presents a great problem in almost every country that produces such waste. The main problem is not a technical one, but socio-psychological, namely the acceptability of this kind of repository. In general, people are opposed to any such kind of facility in their vicinity (NIMBY). In this study we try to establish the factors that influence people's behavior regarding the construction of a radioactive waste repository in their local community, with the use of Ajzen's model of planned behavior. Two different scenarios about the construction of a radioactive waste repository in their community, together with a set of questions were presented to participants from different schools. Data from the survey were analysed by multivariate methods, and a model of relevant behaviour was proposed. From the results it can be seen that different approaches to local community participation in site selection process slightly influence people's attitudes towards the LILW repository, while significant differences in answers were found in the responses which depend on participants' knowledge. Therefore the RAO Agency will further intensify preparation of the relevant communication plan and start with its implementation to support LILW repository site selection process, which will also include educational programme. (author)

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.

VerSi. A method for the quantitative comparison of repository systems

Energy Technology Data Exchange (ETDEWEB)

Kaempfer, T.U.; Ruebel, A.; Resele, G. [AF-Consult Switzerland Ltd, Baden (Switzerland); Moenig, J. [GRS Braunschweig (Germany)

2015-07-01

Decision making and design processes for radioactive waste repositories are guided by safety goals that need to be achieved. In this context, the comparison of different disposal concepts can provide relevant support to better understand the performance of the repository systems. Such a task requires a method for a traceable comparison that is as objective as possible. We present a versatile method that allows for the comparison of different disposal concepts in potentially different host rocks. The condition for the method to work is that the repository systems are defined to a comparable level including designed repository structures, disposal concepts, and engineered and geological barriers which are all based on site-specific safety requirements. The method is primarily based on quantitative analyses and probabilistic model calculations regarding the long-term safety of the repository systems under consideration. The crucial evaluation criteria for the comparison are statistical key figures of indicators that characterize the radiotoxicity flux out of the so called containment-providing rock zone (einschlusswirksamer Gebirgsbereich). The key figures account for existing uncertainties with respect to the actual site properties, the safety relevant processes, and the potential future impact of external processes on the repository system, i.e., they include scenario-, process-, and parameter-uncertainties. The method (1) leads to an evaluation of the retention and containment capacity of the repository systems and its robustness with respect to existing uncertainties as well as to potential external influences; (2) specifies the procedures for the system analyses and the calculation of the statistical key figures as well as for the comparative interpretation of the key figures; and (3) also gives recommendations and sets benchmarks for the comparative assessment of the repository systems under consideration based on the key figures and additional qualitative

Nuclide release calculation in the near-field of a reference HLW repository

International Nuclear Information System (INIS)

Lee, Youn Myoung; Hwang, Yong Soo; Kang, Chul Hyung

2004-01-01

The HLW-relevant R and D program for disposal of high-level radioactive waste has been carried out at Korea Atomic Energy Research Institute (KAERI) since early 1997 in order to develop a conceptual Korea Reference Repository System for direct disposal of nuclear spent fuel by the end of 2007. A preliminary reference geologic repository concept considering such established criteria and requirements as waste and generic site characteristics in Korea was roughly envisaged in 2003 focusing on the near-field components of the repository system. According to above basic repository concept, which is similar to that of Swedish KBS-3 repository, the spent fuel is first encapsulated in corrosion resistant canisters, even though the material has not yet been determined, and then emplaced into the deposition holes surrounded by high density bentonite clay in tunnels constructed at a depth of about 500 m in a stable plutonic rock body. Not only to demonstrate how much a reference repository is safe in the generic point of view with several possible scenarios and cases associated with a preliminary repository concept by conducting calculations for nuclide release and transport in the near-field components of the repository, even though enough information has not been available that much yet, but also to show a methodology by which a generic safety assessment could be performed for further development of Korea reference repository concept, nuclide release calculation study strongly seems to be necessary

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.

Continuing Science and Technology at the Proposed Yucca Mountain Repository

International Nuclear Information System (INIS)

Finch, R.J.

2005-01-01

Yucca Mountain, Nevada, was designated in 2002 to be the site for the nation's first permanent geological repository for spent nuclear fuel and high-level radioactive waste. The process of selecting a site for the repository began nearly 25 years ago with passage of the Nuclear Waste Policy Act in 1982. The Department of Energy (DOE) is responsible for submitting a license application to the Nuclear Regulatory Commission for constructing and operating the repository, and DOE's Office of Civilian Radioactive Waste Management (OCRWM) is charged with carrying out this action. The use of multiple natural and engineered barriers in the current repository design are considered by OCRWM to be sufficiently robust to warrant license approval; however, potential design enhancements and increased understanding of both natural and engineered barriers, especially over the long time frames during which the waste is to remain isolated from human contact continue to be examined. The Office of Science and Technology and International (OST andI) was created within OCRWM to help explore novel technologies that might lower overall costs and to develop a greater understanding of processes relevant to the long-term performance of the repository. A brief overview of Yucca Mountain, and the role that OST andI has in identifying technological or scientific advances that could make repository operations more efficient or performance more robust, will be presented. It is important to note, however, that adopting any of OST andI's technological or scientific developments will be at the discretion of OCRWM's Office of Repository Development (ORD)

Thermal analyses of spent nuclear fuel repository

International Nuclear Information System (INIS)

Ikonen, K.

2003-06-01

This report contains the temperature dimensioning of the KBS-3V type 1- or 2-panel repository based on the rock properties measured from the Olkiluoto investigations. The report describes first the development of a calculation methodology for the thermal analysis of a repository for nuclear fuel. The disposed canisters produce residual heat due to decay (or disintegration) of radioactive products. The decay heat is conducted to surrounding rock mass. The methods were applied to determine the effect of different parameters on the highest canister temperature and to support the planning, dimensioning and operation of the repository. The thermal diffusivity of the rock is low and the heat released from the canisters is spread into the surrounding rock volume quite slowly causing thermal gradient in the rock close to canisters and the canister temperature is increased remarkably. The maximum temperature on the canister surface is limited to the design temperature of +100 deg C. However, due to uncertainties in thermal analysis parameters (like scattering in rock conductivity) the allowable calculated maximum canister temperature is set to 90 deg C causing a safety margin of 10 deg C. The allowable temperature is controlled by the spacing between adjacent canisters, adjacent tunnels and the distance between separate panels of the repository and the pre-cooling time affecting power of the canisters. Because of the fact that the disposal operation takes several decades, the moment of disposal of an individual canister in addition to the location has an influence on the maximum temperature in the canister. Also, a second disposal panel in the repository has a thermal interaction with the other panel. This interaction is expressed after a few decades at the strongest. It became apparent that the temperature of canister surfaces can be determined by analytic line heat source model much more efficiently than by numerical analysis, if the analytic model is first verified and

Low level waste repositories

International Nuclear Information System (INIS)

Hill, P.R.H.; Wilson, M.A.

1983-11-01

Factors in selecting a site for low-level radioactive waste disposal are discussed. South Australia has used a former tailings dam in a remote, arid location as a llw repository. There are also low-level waste disposal procedures at the Olympic Dam copper/uranium project

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...

Modulation of cigarette smoke-related end-points in mutagenesis and carcinogenesis

International Nuclear Information System (INIS)

De Flora, Silvio; D'Agostini, Francesco; Balansky, Roumen; Camoirano, Anna; Bennicelli, Carlo; Bagnasco, Maria; Cartiglia, Cristina; Tampa, Elena; Longobardi, Maria Grazia; Lubet, Ronald A.; Izzotti, Alberto

2003-01-01

The epidemic of lung cancer and the increase of other tumours and chronic degenerative diseases associated with tobacco smoking have represented one of the most dramatic catastrophes of the 20th century. The control of this plague is one of the major challenges of preventive medicine for the next decades. The imperative goal is to refrain from smoking. However, chemoprevention by dietary and/or pharmacological agents provides a complementary strategy, which can be targeted not only to current smokers but also to former smokers and passive smokers. This article summarises the results of studies performed in our laboratories during the last 10 years, and provides new data generated in vitro, in experimental animals and in humans. We compared the ability of 63 putative chemopreventive agents to inhibit the bacterial mutagenicity of mainstream cigarette smoke. Modulation by ethanol and the mechanisms involved were also investigated both in vitro and in vivo. Several studies evaluated the effects of dietary chemopreventive agents towards smoke-related intermediate biomarkers in various cells, tissues and organs of rodents. The investigated end-points included metabolic parameters, adducts to haemoglobin, bulky adducts to nuclear DNA, oxidative DNA damage, adducts to mitochondrial DNA, apoptosis, cytogenetic damage in alveolar macrophages, bone marrow and peripheral blood erytrocytes, proliferation markers, and histopathological alterations. The agents tested in vivo included N-acetyl-L-cysteine, 1,2-dithiole-3-thione, oltipraz, phenethyl isothiocyanate, 5,6-benzoflavone, and sulindac. We started applying multigene expression analysis to chemoprevention research, and postulated that an optimal agent should not excessively alter per se the physiological background of gene expression but should be able to attenuate the alterations produced by cigarette smoke or other carcinogens. We are working to develop an animal model for the induction of lung tumours following exposure

DRIVER: Building a Sustainable Infrastructure of European Scientific Repositories

CERN Multimedia

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...

DRIVER Building a Sustainable Infrastructure of European Scientific Repositories

CERN Document Server

CERN. Geneva; Hagemann, Melissa

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 inf...

An OAI repository centric peer-review model

CERN Multimedia

CERN. Geneva

2005-01-01

Pre-print repositories have seen a significant increase in use over the past fifteen years across multiple research domains. Researchers are beginning to develop applications capable of using these repositories to assist the scientific community above and beyond the pure dissemination of information. The contributions set forth by this paper emphasize a deconstructed publication model where in which the peer-review certification phase of a pre-print is mediated by an OAI-compliant peer-review service. This peer-review service uses a social-network algorithm for determining potential reviewers for a submitted manuscript and for weighting the influence of each participating reviewer’s evaluations. The paper also provides a set of peer-review specific metadata tags that can accompany a pre-prints existing metadata record. The combinations of these contributions provide a unique repository-centric peer-review model within the framework of the current OAI standards existing today.

Developing criteria to establish Trusted Digital Repositories

Science.gov (United States)

Faundeen, John L.

2017-01-01

This paper details the drivers, methods, and outcomes of the U.S. Geological Survey’s quest to establish criteria by which to judge its own digital preservation resources as Trusted Digital Repositories. Drivers included recent U.S. legislation focused on data and asset management conducted by federal agencies spending $100M USD or more annually on research activities. The methods entailed seeking existing evaluation criteria from national and international organizations such as International Standards Organization (ISO), U.S. Library of Congress, and Data Seal of Approval upon which to model USGS repository evaluations. Certification, complexity, cost, and usability of existing evaluation models were key considerations. The selected evaluation method was derived to allow the repository evaluation process to be transparent, understandable, and defensible; factors that are critical for judging competing, internal units. Implementing the chosen evaluation criteria involved establishing a cross-agency, multi-disciplinary team that interfaced across the organization. 

WORKSHOP ON DEVELOPMENT OF RADIONUCLIDE GETTERS FOR THE YUCCA MOUNTAIN WASTE REPOSITORY: PROCEEDINGS

International Nuclear Information System (INIS)

K.C. Holt

2006-01-01

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 4 - but are not expected to be durable. On the other hand, durable materials, such as

Potential cancer chemopreventive agents from Arbutus unedo.

Science.gov (United States)

Carcache-Blanco, Esperanza J; Cuendet, Muriel; Park, Eun Jung; Su, Bao-Ning; Rivero-Cruz, J Fausto; Farnsworth, Norman R; Pezzuto, John M; Douglas Kinghorn, A

2006-04-01

A phytochemical study of the petroleum ether and ethyl acetate extracts of the entire plant of Arbutus unedo led to the isolation of a new sterol, 7beta-hydroxystigmast-4-en-3-one (1), and nine known compounds of the flavan, steroid, and terpenoid types. The structure of 1 was determined by spectroscopic data interpretation in combination with molecular modeling calculations. The absolute stereochemistry of C-7 was assigned as S for compound 1 based on the obtained CD spectral data. Activity in the JB6 cell transformation assay was found for pomolic acid 3-acetate (4). All isolates obtained were evaluated in a cyclooxygenase-2 (COX-2) inhibition assay.

Thermo-mechanical effects from a KBS-3 type repository. Performance of pillars between repository tunnels

International Nuclear Information System (INIS)

Hakami, E.; Olofsson, Stig-Olof

2000-03-01

The aim of this study has been to investigate how the rock mass, in the near field of a KBS-3 type repository, will be affected by the excavation of tunnels and deposition holes and the thermal load from the deposited waste. The three-dimensional finite difference program FLAC 3D was used to perform numerical simulation of the rock mass behaviour. The rock mass was modelled as a homogeneous and isotropic continuum. The initial area heat intensity of the repository was assumed to be 10 W/m 2 in all models. The results show that in the middle of the pillar between the repository tunnels the temperature reaches a maximum of about 70 deg C after 55 years of deposition. The extent of areas where the rock is predicted to yield depends on the assumed quality of the rock mass and the initial in-situ stress field. The volume of yielded rock reaches a maximum after about 200 years after deposition. For a rock mass with internal friction angle of 45 deg and cohesion of 5 MPa (using a Mohr-Coulomb material model), the extent of yielded rock is limited to about 1.5 m behind the excavation periphery. The largest rock displacements are found in the tunnel floor at the upper part of the deposition holes. Tension and shear failure in the periphery of the excavations is predicted to occur during the rock excavation, with a depth extension depending on the magnitude and orientation of the in-situ stresses, as well as on the rock mass quality. Both the excavation effects and the then-no-mechanical effects are smallest when the major principal stress is oriented parallel with the deposition tunnels. The maximum convergence between tunnel walls was calculated to occur after 200 years and be about 9 mm, in the model assuming a rock mass with 5 MPa cohesion, 45 deg internal friction angle and maximum horizontal stress perpendicular to the tunnel. In this study confining effects from the buffer and backfill material was neglected. The effective stress concept was used in most of the models

Licensing information needs for a high-level waste repository

International Nuclear Information System (INIS)

Wright, R.J.; Greeves, J.T.; Logsdon, M.J.

1985-01-01

The information needs for licensing findings during the development of a repository for high-level waste (HLW) are described. In particular, attention is given to the information and needs to demonstrate, for construction authorization purposes: repository constructibility, waste retrievability, waste containment, and waste isolation

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…

Microsoft Repository Version 2 and the Open Information Model.

Science.gov (United States)

Bernstein, Philip A.; Bergstraesser, Thomas; Carlson, Jason; Pal, Shankar; Sanders, Paul; Shutt, David

1999-01-01

Describes the programming interface and implementation of the repository engine and the Open Information Model for Microsoft Repository, an object-oriented meta-data management facility that ships in Microsoft Visual Studio and Microsoft SQL Server. Discusses Microsoft's component object model, object manipulation, queries, and information…

Reduction of HLW repository environmental impact by Na-Cooled FBR

International Nuclear Information System (INIS)

Ahn, Joonhong; Ikegami, Tetsuo

2005-01-01

The present study proposes the total toxicity index of radionuclides that have accumulated in the region exterior to the repository as the environmental impact measure. The measure is quantitatively evaluated by a radionuclide transport models that incorporate the effects of canister-array configuration and the initial mass loading in the waste canister. With the measure, it is demonstrated that the environmental impact of the repository can be effectively reduced by reduction of the initial mass loading resulting from FBR deployment and change in the canister-array configuration in the repository. The rate of increase in the environmental impact with the increase in the repository size can be reduced by reducing the initial mass loading of Np and its precursors. (author)

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.

The main demands and criteria for building site choice for radioactive waste repositories

International Nuclear Information System (INIS)

Angelova, R.; Sandul, G.A.; Sen'ko, T.Ya.

2002-01-01

There are considered the main demands of building site choice for RAW repositories. At this the accent is placed on geological repositories (underground repositories of geological type) and near surface repositories assigned to disposal of low- and intermediate-level short- and mediate-lived radionuclides. These demands are conditionally separated into two blocks: account of social development of the adjoining territories; account of natural factors characterizing building site. Further there are discussed the questions of anthropogenous influence on a safety functioning of RAW repositories and of urgency of stable development of the adjoining territories. In context of the Ukrainian and other states nuclear laws there is also considered the lawful aspect defining the building site choice for RAW repositories