WorldWideScience

Sample records for sustainability proliferation resistance

  1. Proliferation resistance of advanced sustainable nuclear fuel cycles

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, H.E.; Lineberry, M.J.; Aumeier, S.E.; McFarlane, H.F. [Argonne National Lab.-West (United States)

    2001-07-01

    Intrinsic and extrinsic proliferation barriers of a pyro-process-based nuclear fuel cycle are discussed. While technical characteristics of the process raise new challenges for safeguards, others naturally facilitate the implementation of more integrated schemes for unattended continuous monitoring. In particular, the concept of operations accountability and model-assisted methods are revisited. While traditional safeguards constructs, such as material control and accountability, place greater emphasis on input/output characterization of nuclear processes, a model- based discrete event accountability approach could explicitly verify not only facility use but also internal operational dynamics. Under the proposed remote integral safeguards approach, transparency can be achieved efficiently, without divulging competitive or national security sensitive information. (author)

  2. Proliferation resistance fuel cycle technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Ko, W. I

    1999-02-01

    The issues of dual use in nuclear technology are analysed for nuclear fuel cycle with special focus on uranium enrichment and spent fuel reprocessing which are considered as the most sensitive components in terms of vulnerability to diversion. Technical alternatives to mitigrate the vulnerability, as has been analysed in depth during the NASAP and INFCE era in the late seventies, are reviewed to characterize the DUPIC fuel cycle alternative. On the other hand, the new realities in nuclear energy including the disposition of weapon materials as a legacy of cold war are recast in an angle of nuclear proliferation resistance and safeguards with a discussion on the concept of spent fuel standard concept and its compliance with the DUPIC fuel cycle technology. (author)

  3. Proliferation resistance: issues, initiatives and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, Joseph F [Los Alamos National Laboratory

    2009-01-01

    The vision of a nuclear renaissance has highlighted the issue of proliferation resistance. The prospects for a dramatic growth in nuclear power may depend on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance. The GenIV International Forum (GIF) and others have devoted attention and resources to proliferation resistance. However, the hope of finding a way to make the peaceful uses of nuclear energy resistant to proliferation has reappeared again and again in the history of nuclear power with little practical consequence. The concept of proliferation resistance has usually focused on intrinsic (technological) as opposed to extrinsic (institutional) factors. However, if there are benefits that may yet be realized from reactors and other facilities designed to minimize proliferation risks, it is their coupling with effective safeguards and other nonproliferation measures that likely will be critical. Proliferation resistance has also traditionally been applied only to state threats. Although there are no technologies that can wholly eliminate the risk of proliferation by a determined state, technology can play a limited role in reducing state threats and perhaps in eliminating many non-state threats. These and other issues are not academic. They affect efforts to evaluate proliferation resistance, including the methodology developed by GIF's Proliferation Resistance and Physical Protection (PR&PP) Working Group as well as the proliferation resistance initiatives that are being pursued or may be developed in the future. This paper will offer a new framework for thinking about proliferation resistance issues, including the ways the output of the methodology could be developed to inform the decisions that states, the International Atomic Energy (IAEA) and others will have to make in order to fully realize the promise of a nuclear renaissance.

  4. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    Energy Technology Data Exchange (ETDEWEB)

    Patricia Paviet-Hartmann; Gary Cerefice; Marcela Stacey; Steven Bakhtiar

    2011-05-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate – and should not be equated -with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. . Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R&D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  5. Proliferation Resistant Nuclear Reactor Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Gray, L W; Moody, K J; Bradley, K S; Lorenzana, H E

    2011-02-18

    Global appetite for fission power is projected to grow dramatically this century, and for good reason. Despite considerable research to identify new sources of energy, fission remains the most plentiful and practical alternative to fossil fuels. The environmental challenges of fossil fuel have made the fission power option increasingly attractive, particularly as we are forced to rely on reserves in ecologically fragile or politically unstable corners of the globe. Caught between a globally eroding fossil fuel reserve as well as the uncertainty and considerable costs in the development of fusion power, most of the world will most likely come to rely on fission power for at least the remainder of the 21st century. Despite inevitable growth, fission power faces enduring challenges in sustainability and security. One of fission power's greatest hurdles to universal acceptance is the risk of potential misuse for nefarious purposes of fissionable byproducts in spent fuel, such as plutonium. With this issue in mind, we have discussed intrinsic concepts in this report that are motivated by the premise that the utility, desirability, and applicability of nuclear materials can be reduced. In a general sense, the intrinsic solutions aim to reduce or eliminate the quantity of existing weapons usable material; avoid production of new weapons-usable material through enrichment, breeding, extraction; or employ engineering solutions to make the fuel cycle less useful or more difficult for producing weapons-usable material. By their nature, these schemes require modifications to existing fuel cycles. As such, the concomitants of these modifications require engagement from the nuclear reactor and fuel-design community to fully assess their effects. Unfortunately, active pursuit of any scheme that could further complicate the spread of domestic nuclear power will probably be understandably unpopular. Nevertheless, the nonproliferation and counterterrorism issues are paramount

  6. Proliferation resistance assessment of high temperature gas reactors

    Energy Technology Data Exchange (ETDEWEB)

    Chikamatsu N, M. A. [Instituto Tecnologico y de Estudios Superiores de Monterrey, Campus Santa Fe, Av. Carlos Lazo No. 100, Santa Fe, 01389 Mexico D. F. (Mexico); Puente E, F., E-mail: midori.chika@gmail.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2014-10-15

    The Generation IV International Forum has established different objectives for the new generation of reactors to accomplish. These objectives are focused on sustain ability, safety, economics and proliferation resistance. This paper is focused on how the proliferation resistance of the High Temperature Gas Reactors (HTGR) is assessed and the advantages that these reactors present currently. In this paper, the focus will be on explaining why such reactors, HTGR, can achieve the goals established by the GIF and can present a viable option in terms of proliferation resistance, which is an issue of great importance in the field of nuclear energy generation. The reason why the HTGR are being targeted in this writing is that these reactors are versatile, and present different options from modular reactors to reactors with the same size as the ones that are being operated today. Besides their versatility, the HTGR has designed features that might improve on the overall sustain ability of the nuclear reactors. This is because the type of safety features and materials that are used open up options for industrial processes to be carried out; cogeneration for instance. There is a small section that mentions how HTGR s are being developed in the international sector in order to present the current world view in this type of technology and the further developments that are being sought. For the proliferation resistance section, the focus is on both the intrinsic and the extrinsic features of the nuclear systems. The paper presents a comparison between the features of Light Water Reactors (LWR) and the HTGR in order to be able to properly compare the most used technology today and one that is gaining international interest. (Author)

  7. Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

    Energy Technology Data Exchange (ETDEWEB)

    Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

    1979-01-19

    This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables.

  8. Sustainability of CD24 expression, cell proliferation and migration, cisplatin-resistance, and caspase-3 expression during mesenchymal-epithelial transition induced by the removal of TGF-β1 in A549 lung cancer cells.

    Science.gov (United States)

    Kim, Seong-Kwan; Park, Jin-A; Zhang, Dan; Cho, Sang-Hyun; Yi, Hee; Cho, Soo-Min; Chang, Byung-Joon; Kim, Jin-Suk; Shim, Jae-Han; Abd El-Aty, A M; Shin, Ho-Chul

    2017-08-01

    Epithelial-mesenchymal transition (EMT) is a notable mechanism underlying cancer cell metastasis. Transforming growth factor β1 (TGF-β1) has been used to induce EMT; however, there is a lack of information regarding the role of TGF-β1 in mesenchymal-epithelial transition (MET). In the present study, EMT was induced in A549 lung cancer cells using TGF-β1 (TGF-β1-treated group) and MET was induced sequentially from the TGF-β1-treated group by removing the TGF-β1 (MET/return group). Untreated A549 lung cancer cells were used as a control. Characteristic features, including cancer stem cell markers [cluster of differentiation (CD)24, CD44 and CD133], cell proliferation and migration and diverse intracellular mechanisms, were observed in all groups. Using western blot analysis, the TGF-β1-treated group demonstrated increased vimentin and reduced E-cadherin expression, whereas the MET/return group demonstrated the opposite trend. Among cancer stem cell markers, the population of CD24low cells was reduced in the TGF-β1-treated group. Furthermore, the G2/M phase cell cycle population, cisplatin-sensitivity, and cell proliferation and migration ability were increased in the TGF-β1-treated group. These features were unaltered in the MET/return group when compared to the TGF-β1-treated group. Immunoblotting revealed an increase in the levels of SMAD3, phosphorylated SMAD3, phosphorylated extracellular signal-regulated kinase and caspase-3, and a decrease in active caspase-3 levels in the TGF-β1-treated group. Increased caspase-3 and reduced active caspase-3 levels were observed in the MET/return group, similar to those in the TGF-β1-treated group; however, levels of other signalling proteins were unchanged compared with the control group. EMT induced by TGF-β1 was not preserved; however, stemness-associated properties (CD24 expression, caspase-3 expression, cell proliferation and cisplatin-resistance) were sustained following removal of TGF-β1.

  9. Enhancing BWR proliferation resistance fuel with minor actinides

    Science.gov (United States)

    Chang, Gray S.

    2009-03-01

    To reduce spent fuel for storage and enhance the proliferation resistance for the intermediate-term, there are two major approaches (a) increase the discharged spent fuel burnup in the advanced light water reactor- LWR (Gen-III Plus), which not only can reduce the spent fuel for storage, but also increase the 238Pu isotopes ratio to enhance the proliferation resistance, and (b) use of transuranic nuclides ( 237Np and 241Am) in the high burnup fuel, which can drastically increase the proliferation resistance isotope ratio of 238Pu/Pu. For future advanced nuclear systems, minor actinides (MA) are viewed more as a resource to be recycled, and transmuted to less hazardous and possibly more useful forms, rather than simply disposed of as a waste stream in an expensive repository facility. As a result, MAs play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors to the reactivity control of the systems into which they are incorporated. In the study, a typical boiling water reactor (BWR) fuel unit lattice cell model with UO 2 fuel pins will be used to investigate the effectiveness of minor actinide reduction approach (MARA) for enhancing proliferation resistance and improving the fuel cycle performance in the intermediate-term goal for future nuclear energy systems. To account for the water coolant density variation from the bottom (0.76 g/cm 3) to the top (0.35 g/cm 3) of the core, the axial coolant channel and fuel pin were divided to 24 nodes. The MA transmutation characteristics at different elevations were compared and their impact on neutronics criticality discussed. The concept of MARA, which involves the use of transuranic nuclides ( 237Np and/or 241Am), significantly increases the 238Pu/Pu ratio for proliferation resistance, as well as serves as a burnable absorber to hold-down the initial excess reactivity. It is believed that MARA can play an important role in

  10. Sustainability transition dynamics: Towards overcoming policy resistance

    OpenAIRE

    Gooyert, V. de; Rouwette, E.A.J.A.; van Kranenburg, H.L.; Freeman, R.E.; Breen, H.J. van

    2016-01-01

    Sustainability transitions receive major scholarly attention, often explicitly with the intention to develop policy recommendations aimed towards progressing such transitions. Despite these efforts, many implemented transition policies have not been able to meet expectations. This tendency of systems to defeat the policies that have been designed to improve them is known as ‘policy resistance’. This paper addresses the question how we can explain the persistence of policy resistance in the co...

  11. Proliferation resistances of Generation IV recycling facilities for nuclear fuel

    OpenAIRE

    Åberg Lindell, Matilda

    2013-01-01

    The effects of global warming raise demands for reduced CO2 emissions, whereas at the same time the world’s need for energy increases. With the aim to resolve some of the difficulties facing today’s nuclear power, striving for safety, sustainability and waste minimization, a new generation of nuclear energy systems is being pursued: Generation IV. New reactor concepts and new nuclear facilities should be at least as resistant to diversion of nuclear material for weapons production, as were th...

  12. PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION WORKING GROUP: METHODOLOGY AND APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Bari R. A.; Whitlock, J.; Therios, I.U.; Peterson, P.F.

    2012-11-14

    We summarize the technical progress and accomplishments on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of Generation IV nuclear energy systems. We intend the results of the evaluations performed with the methodology for three types of users: system designers, program policy makers, and external stakeholders. The PR and PP Working Group developed the methodology through a series of demonstration and case studies. Over the past few years various national and international groups have applied the methodology to nuclear energy system designs as well as to developing approaches to advanced safeguards.

  13. Sustained proliferation in cancer: mechanisms and novel therapeutic targets

    Science.gov (United States)

    Arzumanyan, Alla; Kulathinal, Rob J.; Blain, Stacy W.; Holcombe, Randall F.; Mahajna, Jamal; Marino, Maria; Martinez-Chantar, Maria L.; Nawroth, Roman; Sanchez-Garcia, Isidro; Sharma, Dipali; Saxena, Neeraj K.; Singh, Neetu; Vlachostergios, Panagiotis J.; Guo, Shanchun; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Nowsheen, Somaira

    2016-01-01

    Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). This data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression. PMID:25892662

  14. Sustainably Sourced, Thermally Resistant, Radiation Hard Biopolymer

    Science.gov (United States)

    Pugel, Diane

    2011-01-01

    This material represents a breakthrough in the production, manufacturing, and application of thermal protection system (TPS) materials and radiation shielding, as this represents the first effort to develop a non-metallic, non-ceramic, biomaterial-based, sustainable TPS with the capability to also act as radiation shielding. Until now, the standing philosophy for radiation shielding involved carrying the shielding at liftoff or utilizing onboard water sources. This shielding material could be grown onboard and applied as needed prior to different radiation landscapes (commonly seen during missions involving gravitational assists). The material is a bioplastic material. Bioplastics are any combination of a biopolymer and a plasticizer. In this case, the biopolymer is a starch-based material and a commonly accessible plasticizer. Starch molecules are composed of two major polymers: amylase and amylopectin. The biopolymer phenolic compounds are common to the ablative thermal protection system family of materials. With similar constituents come similar chemical ablation processes, with the potential to have comparable, if not better, ablation characteristics. It can also be used as a flame-resistant barrier for commercial applications in buildings, homes, cars, and heater firewall material. The biopolymer is observed to undergo chemical transformations (oxidative and structural degradation) at radiation doses that are 1,000 times the maximum dose of an unmanned mission (10-25 Mrad), indicating that it would be a viable candidate for robust radiation shielding. As a comparison, the total integrated radiation dose for a three-year manned mission to Mars is 0.1 krad, far below the radiation limit at which starch molecules degrade. For electron radiation, the biopolymer starches show minimal deterioration when exposed to energies greater than 180 keV. This flame-resistant, thermal-insulating material is non-hazardous and may be sustainably sourced. It poses no hazardous

  15. A Comparison of Proliferation Resistance Measures of Misuse Scenarios Using a Markov Approach

    Energy Technology Data Exchange (ETDEWEB)

    Yue,M.; Cheng, L.-Y.; Bari, R.

    2008-05-11

    Misuse of declared nuclear facilities is one of the important proliferation threats. The robustness of a facility against these threats is characterized by a number of proliferation resistance (PR) measures. This paper evaluates and compares PR measures for several misuse scenarios using a Markov model approach to implement the pathway analysis methodology being developed by the PR&PP (Proliferation Resistance and Physical Protection) Expert Group. Different misue strategies can be adopted by a proliferator and each strategy is expected to have different impacts on the proliferator's success. Selected as the probabilistic measure to represent proliferation resistance, the probabilities of the proliferator's success of misusing a hypothetical ESFR (Example Sodium Fast Reactor) facility system are calculated using the Markov model based on the pathways constructed for individual misuse scenarios. Insights from a comparison of strategies that are likely to be adopted by the proliferator are discussed in this paper.

  16. Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2000-07-01

    This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity.

  17. Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume II. Proliferation resistance

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Volume II assesses proliferation resistance. Chapters are devoted to: assessment of civilian nuclear systems (once-through fuel-cycle systems, closed fuel cycle systems, research reactors and critical facilities); assessment of associated sensitive materials and facilities (enrichment, problems with storage of spent fuel and plutonium content, and reprocessing and refabrication facilities); and safeguards for alternative fuel cycles.

  18. Establishment of Assessment Methodology Improvement of IAEA INPRO Proliferation Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. H.; Yang, M. S.; Song, K. C.; Ko, W. I.; Kim, H. D.; Kim, Y. I.; Rhee, B. W.; Kim, H. T.

    2008-03-15

    For the development of assessment methodology of acquisition and diversion pathway of nuclear material, the PR assessment methodology which has been developed by GEN-IV PR and PP group was reviewed regarding the acquisition and diversion pathway of nuclear material and we proposed the research areas to develop the model of acquisition and diversion pathway of nuclear material including misuse of fuel cycle facilities and one of the IAEA INPRO CRPs which is aiming to develop its model. From the present study, its preliminary model for acquisition and diversion pathway of nuclear material was obtained. For preliminary evaluation of DUPIC system using methodology of acquisition/diversion pathway of nm and review of pyro-processing system characteristics, the research direction and work procedure was established to develop the assessment methodology of User Requirement 4 of INPRO PR by; 1) selection of the possible pathway to acquire and divert the nuclear material of DUPIC system, 2) the analysis of selected pathway, 3) the development of the assessment methodology of robustness and multiplicity of an INS. And, the PR characteristics and process/material flow analysis of the Pyro-processing system were preliminarily studied. For establishment of R and D direction for an INS and supporting international cooperation research, the collaborative research project titled as 'Acquisition and Diversion pathway analysis of Proliferation Resistance' as one of activities of IAEA INPRO was proposed, since Korean Government decided to actively support the IAEA INPRO. In order to review and clarify the Terms of Reference (TOR) of a Korean Proposed Collaborative Project (ROK1), two INPRO Consultancy Meetings were held. Its results were presented at two INPRO Steering Committees and the finalized TOR of Korean Proposal submit the 12-th INPRO Steering Committee Meeting which was held Dec. 3-5 2007. Four participants including USA, Canada, China and European Community (EC

  19. Underpinning sustainable vector control through informed insecticide resistance management.

    Science.gov (United States)

    Thomsen, Edward K; Strode, Clare; Hemmings, Kay; Hughes, Angela J; Chanda, Emmanuel; Musapa, Mulenga; Kamuliwo, Mulakwa; Phiri, Faustina N; Muzia, Lucy; Chanda, Javan; Kandyata, Alister; Chirwa, Brian; Poer, Kathleen; Hemingway, Janet; Wondji, Charles S; Ranson, Hilary; Coleman, Michael

    2014-01-01

    There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.

  20. Sustainability transition dynamics: Towards overcoming policy resistance

    NARCIS (Netherlands)

    Gooyert, V. de; Rouwette, E.A.J.A.; Kranenburg, H.L. van; Freeman, R.E.; Breen, H.J. van

    2016-01-01

    Sustainability transitions receive major scholarly attention, often explicitly with the intention to develop policy recommendations aimed towards progressing such transitions. Despite these efforts, many implemented transition policies have not been able to meet expectations. This tendency of

  1. Tanoak resistance: can it be used to sustain populations?

    Science.gov (United States)

    Katherine J. Hayden; Alex Lundquist; Douglas J. Schmidt; Richard A. Sniezko; Susan J. Frankel; Matteo. Garbelotto

    2010-01-01

    Tanoak (Lithocarpus densiflorus) trees are among Phytophthora ramorum’s most susceptible hosts. Extensive mortality in this species has led researchers to question whether selective breeding for resistance can be used to sustain populations; the answer depends on the extent and heritability of pathogen resistance within the...

  2. Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

    DEFF Research Database (Denmark)

    Perea, Daniel; Guiu, Jordi; Hudry, Bruno

    2017-01-01

    site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop...... role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders...

  3. Proliferation resistance assessment of various methods of spent nuclear fuel storage and disposal

    Science.gov (United States)

    Kollar, Lenka

    Many countries are planning to build or already are building new nuclear power plants to match their growing energy needs. Since all nuclear power plants handle nuclear materials that could potentially be converted and used for nuclear weapons, they each present a nuclear proliferation risk. Spent nuclear fuel presents the largest build-up of nuclear material at a power plant. This is a proliferation risk because spent fuel contains plutonium that can be chemically separated and used for a nuclear weapon. The International Atomic Energy Agency (IAEA) safeguards spent fuel in all non-nuclear weapons states that are party to the Non-Proliferation Treaty. Various safeguards methods are in use at nuclear power plants and research is underway to develop safeguards methods for spent fuel in centralized storage or underground storage and disposal. Each method of spent fuel storage presents different proliferation risks due to the nature of the storage method and the safeguards techniques that are utilized. Previous proliferation resistance and proliferation risk assessments have mainly compared nuclear material through the whole fuel cycle and not specifically focused on spent fuel storage. This project evaluates the proliferation resistance of the three main types of spent fuel storage: spent fuel pool, dry cask storage, and geological repository. The proliferation resistance assessment methodology that is used in this project is adopted from previous work and altered to be applicable to spent fuel storage. The assessment methodology utilizes various intrinsic and extrinsic proliferation-resistant attributes for each spent fuel storage type. These attributes are used to calculate a total proliferation resistant (PR) value. The maximum PR value is 1.00 and a greater number means that the facility is more proliferation resistant. Current data for spent fuel storage in the United States and around the world was collected. The PR values obtained from this data are 0.49 for

  4. Underpinning sustainable vector control through informed insecticide resistance management.

    Directory of Open Access Journals (Sweden)

    Edward K Thomsen

    Full Text Available There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions.A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s.Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.

  5. Proliferation-Resistant Nuclear Power Systems: A Workshop on New Ideas

    Energy Technology Data Exchange (ETDEWEB)

    Schock, R.

    2000-03-01

    The workshop addressed a number of major questions and challenges surrounding the relationship between the future of nuclear power and the broader issue of proliferation of nuclear materials for weapons or other means of nuclear terrorism. This is but one of at least four issues facing the civilian nuclear power industry, the others of note being safety, economics, and environmental impacts including the final disposition of waste. Various authorities attach different levels of significance to these issues, at least some maintaining that proliferation is the greatest, but all agree that they must be examined in parallel. Workshop participants were asked to consider several questions: What do we mean by nuclear proliferation and proliferation resistance? What metrics are useful for assessing proliferation resistance? What are meaningful goals and solutions? Can nuclear power systems and/or sub-systems be developed that are more resistant to proliferation than those in existence or being planned today? What are the barriers to the implementation of such systems? Can these solutions be applied to research, test, and isotope-production reactors?

  6. New concept of proliferation resistant sodium cooled fast reactor

    Energy Technology Data Exchange (ETDEWEB)

    Eliseev, V.A.; Krivitski, I.Y.; Matveev, V.I.; Popov, E.P.; Savitski, V.I.; Tsikunov, A.G. [Institute for Physics and Power Engineering, Obninsk (Russian Federation)

    2001-07-01

    The full text follows. It is proposed the concept of BN-800 sodium cooled fast reactor operating in the closed fuel cycle with special reprocessing technology. The use of nitride fuel allows improving the parameters of reactor safety (internal breeding {approx}1, zero value of sodium void reactivity effect), economy (one refueling per year), ecology (use of nitride enriched by nitrogen-15) and non-proliferation (use of reprocessing without separating the plutonium from uranium). The main difficulty of this type reactor development is that the technical project of BN-800 reactor with MOX fuel was developed. When using the nitride fuel it is necessary to serve (in max extent) the mail technical decisions of this project. This report presents first results on development and justification of the BN-800 reactor with nitride fuel core. (authors)

  7. Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun [Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081 (China); Tan, Wenhua, E-mail: tanwenhua1962@163.com [Department of Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086 (China)

    2015-10-23

    Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

  8. Nuclear proliferation and civilian nuclear power. Report of the Nonproliferation Alternative Systems Assessment Program. Volume II. Proliferation resistance

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    The purpose of this volume is limited to an assessment of the relative effects that particular choices of nuclear-power systems, for whatever reasons, may have on the possible spread of nuclear-weapons capabilities. This volume addresses the concern that non-nuclear-weapons states may be able to initiate efforts to acquire or to improve nuclear-weapons capabilities through civilian nuclear-power programs; it also addresses the concern that subnational groups may obtain and abuse the nuclear materials or facilities of such programs, whether in nuclear-weapons states (NWS's) or nonnuclear-weapons states (NNW's). Accordingly, this volume emphasizes one important factor in such decisions, the resistance of nuclear-power systems to the proliferation of nuclear-weapons capabilities.

  9. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  10. Proliferation resistance for fast reactors and related fuel cycles: issues and impacts

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, Joseph F [Los Alamos National Laboratory

    2010-01-01

    The prospects for a dramatic growth in nuclear power may depend to a significant degree on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance and nuclear materials accountability. The challenges for fast reactors and related fuel cycles are especially critical. They are being explored in the Generation IV Tnternational Forum (GIF) and the Tnternational Atomic Energy Agency's (IAEA's) International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) initiative, as well as by many states that are looking to these systems for the efficient lise of uranium resources and long-term energy security. How do any proliferation risks they may pose compare to other reactors, both existing and under development, and their fuel cycles? Can they be designed with intrinsic (technological) features to make these systems more proliferation resistant? What roles can extrinsic (institutional) features play in proliferation resistance? What are the anticipated safeguards requirements, and will new technologies and approaches need to be developed? How can safeguards be facilitated by the design process? These and other questions require a rethinking of proliferation resistance and the prospects for new technologies and other intrinsic and extrinsic features being developed that are responsive to specific issues for fast reactors and related fuel cycles and to the broader threat environment in which these systems will have to operate. There are no technologies that can wholly eliminate the risk of proliferation by a determined state, but technology and design can playa role in reducing state threats and perhaps in eliminating non-state threats. There will be a significant role for extrinsic factors, especially the various measures - from safeguards and physical protection to export controls - embodied in the international nuclear nonproliferation regime. This paper

  11. An Expert Elicitation of the Proliferation Resistance of Using Small Modular Reactors (SMR) for the Expansion of Civilian Nuclear Systems.

    Science.gov (United States)

    Siegel, Jonas; Gilmore, Elisabeth A; Gallagher, Nancy; Fetter, Steve

    2018-02-01

    To facilitate the use of nuclear energy globally, small modular reactors (SMRs) may represent a viable alternative or complement to large reactor designs. One potential benefit is that SMRs could allow for more proliferation resistant designs, manufacturing arrangements, and fuel-cycle practices at widespread deployment. However, there is limited work evaluating the proliferation resistance of SMRs, and existing proliferation assessment approaches are not well suited for these novel arrangements. Here, we conduct an expert elicitation of the relative proliferation resistance of scenarios for future nuclear energy deployment driven by Generation III+ light-water reactors, fast reactors, or SMRs. Specifically, we construct the scenarios to investigate relevant technical and institutional features that are postulated to enhance the proliferation resistance of SMRs. The experts do not consistently judge the scenario with SMRs to have greater overall proliferation resistance than scenarios that rely on conventional nuclear energy generation options. Further, the experts disagreed on whether incorporating a long-lifetime sealed core into an SMR design would strengthen or weaken proliferation resistance. However, regardless of the type of reactor, the experts judged that proliferation resistance would be enhanced by improving international safeguards and operating several multinational fuel-cycle facilities rather than supporting many more national facilities. © 2017 Society for Risk Analysis.

  12. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Walpen, Thomas; Kalus, Ina [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Schwaller, Juerg [Department of Biomedicine, University of Basel, 4031 Basel (Switzerland); Peier, Martin A. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Battegay, Edouard J. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland); Humar, Rok, E-mail: Rok.Humar@usz.ch [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  13. Framework for Proliferation Resistance and Physical Protection for Nonproliferation Impact Assessments.

    Energy Technology Data Exchange (ETDEWEB)

    Bari,R.

    2008-03-01

    This report describes a framework for proliferation resistance and physical protection evaluation for the fuel cycle systems envisioned in the expansion of nuclear power for electricity generation. The methodology is based on an approach developed as part of the Generation IV technical evaluation framework and on a qualitative evaluation approach to policy factors similar to those that were introduced in previous Nonproliferation Impact Assessments performed by DOE.

  14. Neutronic simulation calculations to assess the proliferation resistance of nuclear technologies; Neutronenphysikalische Simulationsrechnungen zur Proliferationsresistenz nuklearer Technologien

    Energy Technology Data Exchange (ETDEWEB)

    Englert, Matthias

    2009-07-13

    This thesis investigates the proliferation resistance of nuclear technologies on the basis of three case studies. After a brief description of the concept of proliferation resistance the utilized computer codes and methods are presented. The first case study investigates the potential of monolithic fuel for the conversion of one-fuel-element high-flux research reactors from highly enriched to low enriched uranium using the example of the german research reactor FRM-II. The second case study assesses the proliferation potential of future tokamak based fusion reactors by using neutronic simulations of a possible plutonium production. The third example investigates the proliferation potential of spallation neutron sources to produce nuclear weapon relevant material and the proliferation resistance of such facilities. (orig.)

  15. Rage induces hepatocellular carcinoma proliferation and sorafenib resistance by modulating autophagy.

    Science.gov (United States)

    Li, Jun; Wu, Peng-Wen; Zhou, Yuan; Dai, Bo; Zhang, Peng-Fei; Zhang, Yu-Hen; Liu, Yang; Shi, Xiao-Lei

    2018-02-14

    The receptor for advanced glycation end products (Rage) is involved in the development of various tumors and acts as an oncogenic protein. Rage is overexpressed in tumors including hepatocellular carcinoma (HCC). However, the molecular mechanism of Rage in HCC progression and sorafenib resistance remains unclear. In this study, enhanced Rage expression is highly associated proliferation and contributes to sorafenib resistance. Rage deficiency contributed to autophagy induction through activating AMPK/mTOR signaling pathway, which is important for sorafenib response. Moreover, the interactions between Rage and Rage ligands such as high mobility group box 1 (HMGB1) and s100a4 positively increased Rage expression. Our data indicate that Rage may be a potential target for therapeutic intervention in HCC and biomarker for sorafenib resistance.

  16. Very High-Temperature Reactor (VHTR) Proliferation Resistance and Physical Protection (PR&PP)

    Energy Technology Data Exchange (ETDEWEB)

    Moses, David Lewis [ORNL

    2011-10-01

    This report documents the detailed background information that has been compiled to support the preparation of a much shorter white paper on the design features and fuel cycles of Very High-Temperature Reactors (VHTRs), including the proposed Next-Generation Nuclear Plant (NGNP), to identify the important proliferation resistance and physical protection (PR&PP) aspects of the proposed concepts. The shorter white paper derived from the information in this report was prepared for the Department of Energy Office of Nuclear Science and Technology for the Generation IV International Forum (GIF) VHTR Systems Steering Committee (SSC) as input to the GIF Proliferation Resistance and Physical Protection Working Group (PR&PPWG) (http://www.gen-4.org/Technology/horizontal/proliferation.htm). The short white paper was edited by the GIF VHTR SCC to address their concerns and thus may differ from the information presented in this supporting report. The GIF PR&PPWG will use the derived white paper based on this report along with other white papers on the six alternative Generation IV design concepts (http://www.gen-4.org/Technology/systems/index.htm) to employ an evaluation methodology that can be applied and will evolve from the earliest stages of design. This methodology will guide system designers, program policy makers, and external stakeholders in evaluating the response of each system, to determine each system's resistance to proliferation threats and robustness against sabotage and terrorism threats, and thereby guide future international cooperation on ensuring safeguards in the deployment of the Generation IV systems. The format and content of this report is that specified in a template prepared by the GIF PR&PPWG. Other than the level of detail, the key exception to the specified template format is the addition of Appendix C to document the history and status of coated-particle fuel reprocessing technologies, which fuel reprocessing technologies have yet to be

  17. PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan; Zheng, Wei; Wu, Haochen [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Lu, Yan, E-mail: luyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Shen, Pingping, E-mail: ppshen@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Model Animal Research Center (MARC), Nanjing University, Nanjing (China)

    2014-03-10

    Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21{sup Waf1/Cip1} and p27{sup Kip1} descended in PPARγ1{sup S84D} stable HT1080 cell, whereas the expression of p18{sup INK4C} was not changed. Moreover, compared to the PPARγ1{sup S84A}, PPARγ1{sup S84D} up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. - Highlights: • Phosphorylation attenuates PPARγ1 transcriptional activity. • Phosphorylated PPARγ1 promotes HT1080 cells proliferation. • PPARγ1 phosphorylation regulates cell cycle by mediating expression of cell cycle regulators. • PPARγ1 phosphorylation reduces sensitivity to agonist and anticancer drug. • Our findings establish PPARγ1 phosphorylation as a critical event in HT1080

  18. Prevalence and proliferation of antibiotic resistance genes in two municipal wastewater treatment plants.

    Science.gov (United States)

    Mao, Daqing; Yu, Shuai; Rysz, Michal; Luo, Yi; Yang, Fengxia; Li, Fengxiang; Hou, Jie; Mu, Quanhua; Alvarez, P J J

    2015-11-15

    The propagation of antibiotic resistance genes (ARGs) is an emerging health concern worldwide. Thus, it is important to understand and mitigate their occurrence in different systems. In this study, 30 ARGs that confer resistance to tetracyclines, sulfonamides, quinolones or macrolides were detected in two activated sludge wastewater treatment plants (WWTPs) in northern China. Bacteria harboring ARGs persisted through all treatment units, and survived disinfection by chlorination in greater percentages than total Bacteria (assessed by 16S rRNA genes). Although the absolute abundances of ARGs were reduced from the raw influent to the effluent by 89.0%-99.8%, considerable ARG levels [(1.0 ± 0.2) × 10(3) to (9.5 ± 1.8) × 10(5) copies/mL)] were found in WWTP effluent samples. ARGs were concentrated in the waste sludge (through settling of bacteria and sludge dewatering) at (1.5 ± 2.3) × 10(9) to (2.2 ± 2.8) × 10(11) copies/g dry weight. Twelve ARGs (tetA, tetB, tetE, tetG, tetH, tetS, tetT, tetX, sul1, sul2, qnrB, ermC) were discharged through the dewatered sludge and plant effluent at higher rates than influent values, indicating overall proliferation of resistant bacteria. Significant antibiotic concentrations (2%-50% of raw influent concentrations) remained throughout all treatment units. This apparently contributed selective pressure for ARG replication since the relative abundance of resistant bacteria (assessed by ARG/16S rRNA gene ratios) was significantly correlated to the corresponding effluent antibiotic concentrations. Similarly, the concentrations of various heavy metals (which induce a similar bacterial resistance mechanism as antibiotics - efflux pumps) were also correlated to the enrichment of some ARGs. Thus, curtailing the release of antibiotics and heavy metals to sewage systems (or enhancing their removal in pre-treatment units) may alleviate their selective pressure and mitigate ARG proliferation in WWTPs. Copyright © 2015 Elsevier Ltd. All

  19. Anti-proliferation effect of blue light-emitting diodes against antibiotic-resistant Helicobacter pylori.

    Science.gov (United States)

    Ma, Jianwei; Hiratsuka, Takahiro; Etoh, Tsuyoshi; Akada, Junko; Fujishima, Hajime; Shiraishi, Norio; Yamaoka, Yoshio; Inomata, Masafumi

    2017-12-07

    Infection by Helicobacter pylori is implicated in a wide range of upper gastrointestinal diseases. Owing to the rapid emergence of antibiotic-resistant strains of H. pylori, the development of novel treatment modalities for antibiotic-resistant H. pylori infection is a key priority. Blue light-emitting diodes (LED) may represent a unique option owing to their antimicrobial effect. In this study, we aimed to evaluate the anti-proliferative effect of blue LED against antibiotic-resistant H. pylori. Ten antibiotic-resistant strains and one sensitive H. pylori strain were used in this study. After irradiation by blue LED along time course, the viability of H. pylori was evaluated by enumerating colony forming units. Morphological changes in H. pylori were observed using a scanning electron microscope. Reductase activity was measured as an indicator of bacterial cellular activity. Total reactive oxygen species was monitored using fluorescence intensity and fluorescence microscope imaging. After irradiation by blue LED, the numbers of H. pylori in all the strains were significantly reduced compared to control group. The H. pylori exhibited a short rod-shaped morphology after irradiation; no such change was observed in H. pylori not exposed to blue LED. Re-irradiation of surviving strain after the initial irradiation also exhibited the same anti-proliferation effect. After blue LED irradiation, bacterial cellular activity was lower and total reactive oxygen species production was significantly higher in blue LED group, compared to that in control. Blue LED could be a new treatment to eradicate infection with antibiotic-resistant H. pylori. This article is protected by copyright. All rights reserved.

  20. PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells.

    Science.gov (United States)

    Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan; Zheng, Wei; Wu, Haochen; Lu, Yan; Shen, Pingping

    2014-03-10

    Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21(Waf1/Cip1) and p27(Kip1) descended in PPARγ1(S84D) stable HT1080 cell, whereas the expression of p18(INK4C) was not changed. Moreover, compared to the PPARγ1(S84A), PPARγ1(S84D) up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Role of bottom-fermenting brewer's yeast KEX2 in high temperature resistance and poor proliferation at low temperatures.

    Science.gov (United States)

    Yamagishi, Hiromi; Ohnuki, Shinsuke; Nogami, Satoru; Ogata, Tomoo; Ohya, Yoshikazu

    2010-08-01

    Variants of bottom-fermenting brewer's yeast that grew at high temperatures and showed poor proliferation and fermentation at low temperatures were isolated. Similar variants of laboratory yeast were also isolated and found to be incapable of mating. The KEX2 gene was cloned by complementation. It was shown to be responsible for these traits, because a KEX2 disruptant of Saccharomyces cerevisiae (S. cerevisiae) laboratory yeast grew poorly at low temperatures and was resistant to high temperatures. In addition, a Saccharomyces bayanus (S. bayanus)-type KEX2 (Sb-KEX2) disruptant of bottom-fermenting brewer's yeast grew poorly at low temperatures and was resistant to high temperatures. The KEX2 gene product plays an important role in proliferation of yeast at low temperatures, which is an important trait of bottom-fermenting brewer's yeast. These findings advance our understanding of the proliferation of yeast at low temperatures, especially that of bottom-fermenting brewer's yeast.

  2. Assessment of Proliferation Resistance of Closed Nuclear Fuel Cycle System with Sodium Cooled Fast Reactors Using INPRO Evaluation Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young In; Hahn, Do Hee; Won, Byung Chool; Lee, Dong Uk

    2007-11-15

    Using the INPRO methodology, the proliferation resistance of an innovative nuclear energy system(INS) defined as a closed nuclear fuel cycle system consisting of KALIMER and pyroprocessing, has been assessed. Considering a very early development stage of the INS concept, the PR assessment is carried out based on intrinsic features, if required information and data are not available. The PR assessment of KALIMER and JSFR using the INPRO methodology affirmed that an adequate proliferation resistance has been achieved in both INSs CNFC-SFR, considering the assessor's progress and maturity of design development. KALIMER and JSFR are developed or being developed conforming to the targets and criteria defined for developing Gen IV nuclear reactor system. Based on these assessment results, proliferation resistance and physical protection(PR and PP) of KALIMER and JSFR are evaluated from the viewpoint of requirements for future nuclear fuel cycle system. The envisioned INSs CNFC-SFR rely on active plutonium management based on a closed fuel cycle, in which a fissile material is recycled in an integrated fuel cycle facility within proper safeguards. There is no isolated plutonium in the closed fuel cycle. The material remains continuously in a sequence of highly radioactive matrices within inaccessible facilities. The proliferation resistance assessment should be an ongoing analysis that keeps up with the progress and maturity of the design of Gen IV SFR.

  3. Utility of Social Modeling for Proliferation Assessment - Enhancing a Facility-Level Model for Proliferation Resistance Assessment of a Nuclear Enegry System

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Brothers, Alan J.; Gastelum, Zoe N.; Olson, Jarrod; Thompson, Sandra E.

    2009-10-26

    The Utility of Social Modeling for Proliferation Assessment project (PL09-UtilSocial) investigates the use of social and cultural information to improve nuclear proliferation assessments, including nonproliferation assessments, Proliferation Resistance (PR) assessments, safeguards assessments, and other related studies. These assessments often use and create technical information about a host State and its posture towards proliferation, the vulnerability of a nuclear energy system (NES) to an undesired event, and the effectiveness of safeguards. This objective of this project is to find and integrate social and technical information by explicitly considering the role of cultural, social, and behavioral factors relevant to proliferation; and to describe and demonstrate if and how social science modeling has utility in proliferation assessment. This report describes a modeling approach and how it might be used to support a location-specific assessment of the PR assessment of a particular NES. The report demonstrates the use of social modeling to enhance an existing assessment process that relies on primarily technical factors. This effort builds on a literature review and preliminary assessment performed as the first stage of the project and compiled in PNNL-18438. [ T his report describes an effort to answer questions about whether it is possible to incorporate social modeling into a PR assessment in such a way that we can determine the effects of social factors on a primarily technical assessment. This report provides: 1. background information about relevant social factors literature; 2. background information about a particular PR assessment approach relevant to this particular demonstration; 3. a discussion of social modeling undertaken to find and characterize social factors that are relevant to the PR assessment of a nuclear facility in a specific location; 4. description of an enhancement concept that integrates social factors into an existing, technically

  4. Mechanically tuned nanocomposite coating on titanium metal with integrated properties of biofilm inhibition, cell proliferation, and sustained drug delivery.

    Science.gov (United States)

    Mishra, Sandeep K; Teotia, Arun K; Kumar, Ashok; Kannan, Sanjeevi

    2017-01-01

    The clinical success of coated implants in executing biological functions inclusive of sustainable drug release and long term antibacterial activity without antibiotics is critical. To this aim, a nanohybrid of silver nanoparticles (AgNPs) cored in polyvinyl alcohol nanocapsules (Ag-PVA NCs) embedded in chitosan (CS) matrix loaded with anti-inflammatory drug naproxen was prepared. The synthesized nanohybrids that were subjected to coatings on (3-aminopropyl)triethoxysilane (APTES) treated titanium (Ti) metal exhibited dual role of excellent inhibition on biofilm formation and sustained drug release. These dual characteristics are achieved mainly based on intrinsic antibacterial property of AgNPs and differential entrapment of drug in PVA polymeric shell of AgNPs and CS matrix. The coatings also demonstrated enhanced mechanical properties with increasing inorganic filler and stress shielding on Ti metal. The biocompatibility tests involving adhesion, proliferation and differentiation of osteoblast cells demonstrated the efficacy of Ag-PVA NCs embedded in CS matrix as a suitable coating material for orthopedic applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Development status and potential program for development of proliferation-resistant molten-salt reactors

    Energy Technology Data Exchange (ETDEWEB)

    Engel, J.R.; Bauman, H.F.; Dearing, J.F.; Grimes, W.R.; McCoy, H.E. Jr.

    1979-03-01

    Preliminary studies of existing and conceptual molten-salt reactor (MSR) designs have led to the identification of conceptual systems that are technologically attractive when operated with denatured uranium as the principal fissile fuel. These denatured MSRs would also have favorable resource-utilization characteristics and substantial resistance to proliferation of weapons-usable nuclear materials. The report presents a summary of the current status of technology and a discussion of the major technical areas of a possible base program to develop commercial denatured MSRs. The general areas treated are (1) reactor design and development, (2) safety and safety related technology, (3) fuel-coolant behavior and fuel processing, and (4) reactor materials. A substantial development effort could lead to authorization for construction of a molten-salt test reactor about 5 years after the start of the program and operation of the unit about 10 years later. A prototype commercial denatured MSR could be expected to begin operating 25 years from the start of the program. The postulated base program would extend over 32 years and would cost about $700 million (1978 dollars, unescalated). Additional costs to construct the MSTR, $600 million, and the prototype commercial plant, $1470 million, would bring the total program cost to about $2.8 billion. Additional allowances probably should be made to cover contingencies and incidental technology areas not explicitly treated in this preliminary review.

  6. Radiation-induced homotypic cell fusions of innately resistant glioblastoma cells mediate their sustained survival and recurrence.

    Science.gov (United States)

    Kaur, Ekjot; Rajendra, Jacinth; Jadhav, Shailesh; Shridhar, Epari; Goda, Jayant Sastri; Moiyadi, Aliasgar; Dutt, Shilpee

    2015-06-01

    Understanding of molecular events underlying resistance and relapse in glioblastoma (GBM) is hampered due to lack of accessibility to resistant cells from patients undergone therapy. Therefore, we mimicked clinical scenario in an in vitro cellular model developed from five GBM grade IV primary patient samples and two cell lines. We show that upon exposure to lethal dose of radiation, a subpopulation of GBM cells, innately resistant to radiation, survive and transiently arrest in G2/M phase via inhibitory pCdk1(Y15). Although arrested, these cells show multinucleated and giant cell phenotype (MNGC). Significantly, we demonstrate that these MNGCs are not pre-existing giant cells from parent population but formed via radiation-induced homotypic cell fusions among resistant cells. Furthermore, cell fusions induce senescence, high expression of senescence-associated secretory proteins (SASPs) and activation of pro-survival signals (pAKT, BIRC3 and Bcl-xL) in MNGCs. Importantly, following transient non-proliferation, MNGCs escape senescence and despite having multiple spindle poles during mitosis, they overcome mitotic catastrophe to undergo normal cytokinesis forming mononucleated relapse population. This is the first report showing radiation-induced homotypic cell fusions as novel non-genetic mechanism in radiation-resistant cells to sustain survival. These data also underscore the importance of non-proliferative phase in resistant glioma cells. Accordingly, we show that pushing resistant cells into premature mitosis by Wee1 kinase inhibitor prevents pCdk1(Y15)-mediated cell cycle arrest and relapse. Taken together, our data provide novel molecular insights into a multistep process of radiation survival and relapse in GBM that can be exploited for therapeutic interventions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. SUSTAINABILITY OF INSECT RESISTANCE MANAGEMENT STRATEGIES FOR TRANSGENIC BT CORN

    Science.gov (United States)

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  8. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    Science.gov (United States)

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

  9. Demonstration of Three Corrosion-Resistant Sustainable Roofing Systems

    Science.gov (United States)

    2013-06-01

    UV-resistant acrylic binder (Figure 1). The stone chips provide additional protection from heat and abrasion . The “fawn grey” color that was chosen... peeling , chalking, or any other environmental-related degradation. 3.2.2 Attic environment and roof temperature assessments 3.2.2.1 Stone-coated metal

  10. Calcium or resistant starch does not affect colonic epithelial cell proliferation throughout the colon in adenoma patients : A randomized controlled trial

    NARCIS (Netherlands)

    van Gorkom, Britta A P; Karrenbeld, Arend; van der Sluis, Tineke; Zwart, Nynke; van der Meer, Roelof; de Vries, Elisabeth G E; Kleibeuker, Jan H

    2002-01-01

    Patients with a history of sporadic adenomas have increased epithelial cell proliferative activity, an intermediate risk marker for colorectal cancer. Reduction of proliferation by dietary intervention may reflect a decreased colorectal cancer risk. To evaluate whether calcium or resistant starch

  11. Peroxisome Proliferator-Activated Receptors in Regulation of Cytochromes P450: New Way to Overcome Multidrug Resistance?

    Directory of Open Access Journals (Sweden)

    Katerina Cizkova

    2012-01-01

    Full Text Available Embryonic and tumour cells are able to protect themselves against various harmful compounds. In human pathology, this phenomenon exists in the form of multidrug resistance (MDR that significantly deteriorates success of anticancer treatment. Cytochromes P450 (CYPs play one of the key roles in the xenobiotic metabolism. CYP expression could contribute to resistance of cancer cells to chemotherapy. CYP epoxygenases (CYP2C and CYP2J metabolize about 20% of clinically important drugs. Besides of drug metabolism, CYP epoxygenases and their metabolites play important role in embryos, normal body function, and tumors. They participate in angiogenesis, mitogenesis, and cell signaling. It was found that CYP epoxygenases are affected by peroxisome proliferator-activated receptor α (PPARα. Based on the results of current studies, we assume that PPARs ligands may regulate CYP2C and CYP2J and in some extent they may contribute to overcoming of MDR in patients with different types of tumours.

  12. Surge in insect resistance to transgenic crops and prospects for sustainability.

    Science.gov (United States)

    Tabashnik, Bruce E; Carrière, Yves

    2017-10-11

    Transgenic crops have revolutionized insect pest control, but their effectiveness has been reduced by evolution of resistance in pests. We analyzed global monitoring data reported during the first two decades of transgenic crops, with each case representing the responses of one pest species in one country to one insecticidal protein from Bacillus thuringiensis (Bt). The cases of pest resistance to Bt crystalline (Cry) proteins produced by transgenic crops increased from 3 in 2005 to 16 in 2016. By contrast, in 17 other cases there was no decrease in pest susceptibility to Bt crops, including the recently introduced transgenic corn that produces a Bt vegetative insecticidal protein (Vip). Recessive inheritance of pest resistance has favored sustained susceptibility, but even when inheritance is not recessive, abundant refuges of non-Bt host plants have substantially delayed resistance. These insights may inform resistance management strategies to increase the durability of current and future transgenic crops.

  13. Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seong-Su, E-mail: seong-su-han@uiowa.edu [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Han, Sangwoo [Health and Human Physiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Kamberos, Natalie L. [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)

    2014-09-26

    Highlights: • PL inhibits the proliferation of B-ALL cell lines irrespective of GC-resistance. • PL selectively kills B-ALL cells by increasing ROS, but not normal counterpart. • PL does not sensitize majority of B-ALL cells to DEX. • PL represses the network of constitutively activated TFs and modulates their target genes. • PL may serve as a new therapeutic molecule for GC-resistant B-ALL. - Abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL.

  14. FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yi-Fan; Zhao, Jing-Yu; Yue, Hong [Department of Anesthesiology, The First Affiliated Hospital of the General Hospital of CPLA, Beijing 100048 (China); Hu, Ke-Shi; Shen, Hao [Department of Anesthesiology, The General Hospital of CPLA, Beijing 100853 (China); Guo, Zheng-Gang, E-mail: gsgzg304@163.com [Department of Anesthesiology, The First Affiliated Hospital of the General Hospital of CPLA, Beijing 100048 (China); Su, Xiao-Jun, E-mail: lucusebibi@163.com [Department of Anesthesiology, The First Affiliated Hospital of the General Hospital of CPLA, Beijing 100048 (China)

    2015-01-02

    Highlights: • FOXD1 is up-regulated in breast cancer tissues. • FOXD1 promotes breast cancer cell proliferation and chemoresistance by inducing G1 to S transition. • FOXD1 transcriptionally suppresses p27 expression. - Abstract: Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. As a member of the forkhead family, FOXD1 is required during kidney development and its inactivation results in failure of nephron progenitor cells. However, the role of FOXD1 in carcinogenesis and progression is still limited. Here, we reported that FOXD1 is a potential oncogene in breast cancer. We found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increases the ability of cell proliferation and chemoresistance in MCF-7 cells. Furthermore, we observed that FOXD1 induces G1 to S phase transition by targeting p27 expression. Our results suggest that FOXD1 may be a potential therapy target for patients with breast cancer.

  15. Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors

    Directory of Open Access Journals (Sweden)

    Xiaoyan Sheng

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγ and α, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO and db/db mice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptors γ and α (PPARγ/α and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD of PPARγ and PPARα are activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARγ and α, and may be an alternative to PPARγ activator in managing obesity-related diabetes and hyperlipidemia.

  16. Sustainable deployment of QTLs conferring quantitative resistance to crops: first lessons from a stochastic model.

    Science.gov (United States)

    Bourget, Romain; Chaumont, Loïc; Durel, Charles-Eric; Sapoukhina, Natalia

    2015-05-01

    Quantitative plant disease resistance is believed to be more durable than qualitative resistance, since it exerts less selective pressure on the pathogens. However, the process of progressive pathogen adaptation to quantitative resistance is poorly understood, which makes it difficult to predict its durability or to derive principles for its sustainable deployment. Here, we study the dynamics of pathogen adaptation in response to quantitative plant resistance affecting pathogen reproduction rate and its colonizing capacity. We developed a stochastic model for the continuous evolution of a pathogen population within a quantitatively resistant host. We assumed that pathogen can adapt to a host by the progressive restoration of reproduction rate or of colonizing capacity, or of both. Our model suggests that a combination of quantitative trait loci (QTLs) affecting distinct pathogen traits was more durable if the evolution of repressed traits was antagonistic. Otherwise, quantitative resistance that depressed only pathogen reproduction was more durable. In order to decelerate the progressive pathogen adaptation, QTLs that decrease the pathogen's maximum capacity to colonize must be combined with QTLs that decrease the spore production per lesion or the infection efficiency or that increase the latent period. Our theoretical framework can help breeders to develop principles for sustainable deployment of QTLs. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  17. OPTIMIZATION OF HETEROGENEOUS UTILIZATION OF THORIUM IN PWRS TO ENHANCE PROLIFERATION RESISTANCE AND REDUCE WASTE.

    Energy Technology Data Exchange (ETDEWEB)

    TODOSOW,M.; KAZIMI,M.

    2004-08-01

    Issues affecting the implementation, public perception and acceptance of nuclear power include: proliferation, radioactive waste, safety, and economics. The thorium cycle directly addresses the proliferation and waste issues, but optimization studies of core design and fuel management are needed to ensure that it fits within acceptable safety and economic margins. Typical pressurized water reactors, although loaded with uranium fuel, produce 225 to 275 kg of plutonium per gigawatt-year of operation. Although the spent fuel is highly radioactive, it nevertheless offers a potential proliferation pathway because the plutonium is relatively easy to separate, amounts to many critical masses, and does not present any significant intrinsic barrier to weapon assembly. Uranium 233, on the other hand, produced by the irradiation of thorium, although it too can be used in weapons, may be ''denatured'' by the addition of natural, depleted or low enriched uranium. Furthermore, it appears that the chemical behavior of thoria or thoria-urania fuel makes it a more stable medium for the geological disposal of the spent fuel. It is therefore particularly well suited for a once-through fuel cycle. The use of thorium as a fertile material in nuclear fuel has been of interest since the dawn of nuclear power technology due to its abundance and to potential neutronic advantages. Early projects include homogeneous mixtures of thorium and uranium oxides in the BORAX-IV, Indian Point I, and Elk River reactors, as well as heterogeneous mixtures in the Shippingport seed-blanket reactor. However these projects were developed under considerably different circumstances than those which prevail at present. The earlier applications preceded the current proscription, for non-proliferation purposes, of the use of uranium enriched to more than 20 w/o in {sup 235}U, and has in practice generally prohibited the use of uranium highly enriched in {sup 235}U. They were designed when

  18. Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

    Science.gov (United States)

    Zheng, Shui-er; Xiong, Sang; Lin, Feng; Qiao, Guang-lei; Feng, Tao; Shen, Zan; Min, Da-liu; Zhang, Chun-ling; Yao, Yang

    2012-01-01

    Aim: Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. Methods: Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. Results: MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200–1000 ng/mL) inhibited the cell proliferation in time- and concentration-dependent manners. THP (50–500 ng/mL) induced MG63/DOX cell cycle arrest at the G2/M phase in time- and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (200–1000 ng/mL) downregulated cyclin B1 expression, and decreased the phosphorylated Cdc2 at Thr161. Conversely, the treatment increased the phosphorylated Cdc2 at Thr14/Tyr15 and Cdc25C at Ser216, which led to a decrease in Cdc2-cyclin B1 activity. Conclusion: The cytotoxicity of THP to MG63/DOX cells may be in part due to its ability to arrest cell cycle progression at the G2/M phase, which supports the use of THP for managing patients with MDR osteosarcoma. PMID:22580740

  19. Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Judy [Division of Nephrology, Department of Medicine, McMaster University, Juravinski Innovation Tower, Room T3310, St. Joseph' s Hospital, 50 Charlton Ave East, Hamilton, Ontario, Canada L8S 4L8 (Canada); Father Sean O' Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6 (Canada); The Hamilton Centre for Kidney Research (HCKR), St. Joseph' s Hamilton Healthcare, Hamilton, Ontario, Canada L8N 4A6 (Canada); Tang, Damu, E-mail: damut@mcmaster.ca [Division of Nephrology, Department of Medicine, McMaster University, Juravinski Innovation Tower, Room T3310, St. Joseph' s Hospital, 50 Charlton Ave East, Hamilton, Ontario, Canada L8S 4L8 (Canada); Father Sean O' Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6 (Canada); The Hamilton Centre for Kidney Research (HCKR), St. Joseph' s Hamilton Healthcare, Hamilton, Ontario, Canada L8N 4A6 (Canada)

    2014-10-15

    Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistance to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. - Highlights: • Increased survival in DU145 PCSCs following etoposide-induced cytotoxicity. • PCSCs exhibit increased sensitivity to etoposide-induced DDR. • Resistance to cytotoxicity may be due to slower proliferation in PCSCs. • Reduced kinetics to growth factor induced activation of AKT in PCSCs.

  20. Aldo-keto reductase 1B10 and its role in proliferation capacity of drug-resistant cancers

    Directory of Open Access Journals (Sweden)

    Toshiyuki eMatsunaga

    2012-01-01

    Full Text Available The human aldo-keto reductase AKR1B10, originally identified as an aldose reductase-like protein and human small intestine aldose reductase, is a cytosolic NADPH-dependent reductase that metabolizes a variety of endogenous compounds, such as aromatic and aliphatic aldehydes and dicarbonyl compounds, and some drug ketones. The enzyme is highly expressed in solid tumors of several tissues including lung and liver, and as such has received considerable interest as a relevant biomarker for the development of those tumors. In addition, AKR1B10 has been recently reported to be significantly up-regulated in some cancer cell lines (medulloblastoma D341 and colon cancer HT29 acquiring resistance towards chemotherapeutic agents (cyclophosphamide and mitomycin c, suggesting the validity of the enzyme as a chemoresistance marker. Although the detailed information on the AKR1B10-mediated mechanisms leading to the drug resistance process is not well understood so far, the enzyme has been proposed to be involved in functional regulations of cell proliferation and metabolism of drugs and endogenous lipids during the development of chemoresistance. This article reviews the current literature focusing mainly on expression profile and roles of AKR1B10 in the drug resistance of cancer cells. Recent developments of AKR1B10 inhibitors and their usefulness in restoring sensitivity to anticancer drugs are also reviewed.

  1. Dysregulated connexin 43 in HER2-positive drug resistant breast cancer cells enhances proliferation and migration.

    Science.gov (United States)

    Yeh, Elizabeth S; Williams, Christina J; Williams, Carly Bess; Bonilla, Ingrid V; Klauber-DeMore, Nancy; Phillips, Stephanie L

    2017-12-12

    Connexin 43 (Cx43) is a gap junction protein whose function in the development of breast cancer and in breast cancer progression remains unclear. Evidence suggests that Cx43 ( GJA1 ) mRNA and protein expression is altered in breast tumors. However, reports indicate both increased and decreased Cx43 levels in human breast cancer samples. Studies also suggest that loss of Cx43 regulated gap junction intercellular communication is a common feature of breast malignancies that potentially correlates with histological stage. Further evidence suggests that Cx43 ( GJA1 ) mRNA expression is negatively correlated with HER2 positivity but a relationship between Cx43 and HER2 in breast cancer is not well defined. Therefore, in this study, we sought to evaluate the relationship between Cx43 activity, HER2, and drug resistance. Using HER2+ breast cancer cell lines that are sensitive or resistant to HER2 inhibitor, we evaluated Cx43 gap junction function. We found that Cx43 gap junction activity is completely lost in drug resistant HER2-positive (HER2+) breast cancer cells, whereas Cx43 gap junction activity can be restored by Cx43 overexpression in drug sensitive HER2+ cells. Moreover, the dysregulation of Cx43 resulted in increased tumorigenic and migratory capacity of the HER2+ drug resistant breast cancer cells.

  2. Pathway Aggregation in the Risk Assessment of Proliferation Resistance and Physical Protection (PR&PP) of Nuclear Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Aldemir, Tunc [Ohio State Univ., Columbus, OH (United States); Denning, Richard [Ohio State Univ., Columbus, OH (United States); Catalyurek, Umit [Ohio State Univ., Columbus, OH (United States); Yilmaz, Alper [Ohio State Univ., Columbus, OH (United States); Yue, Meng [Brookhaven National Lab. (BNL), Upton, NY (United States); Cheng, Lap-Yan [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-01-23

    The framework for Proliferation Resistance and Physical Protection (PR & PP) evaluation is to define a set of challenges, to obtain the system responses, and to assess the outcomes. The assessment of outcomes heavily relies on pathways, defined as sequences of events or actions that could potentially be followed by a State or a group of individuals in order to achieve a proliferation objective, with the defined threats as initiating events. There may be large number of segments connecting pathway stages (e.g. acquisition, processing, and fabrication for PR) which can lead to even larger number of pathways or scenarios through possible different combinations of segment connections, each with associated probabilities contributing to the overall risk. Clustering of these scenarios in specified stage attribute intervals is important for their tractable analysis and outcome assessment. A software tool for scenario generation and clustering (OSUPR) is developed that utilizes the PRCALC code developed at the Brookhaven National Laboratory for scenario generation and the K- means, mean shift and adaptive mean shift algorithms as possible clustering schemes. The results of the study using the Example Sodium Fast Breeder as an example system show that clustering facilitates the probabilistic or deterministic analysis of scenarios to identify system vulnerabilities and communication of the major risk contributors to stakeholders. The results of the study also show that the mean shift algorithm has the most potential for assisting the analysis of the scenarios generated by PRCALC.

  3. Enhanced satellite cell proliferation with resistance training in elderly men and women

    DEFF Research Database (Denmark)

    Mackey, Abigail; Esmarck, B; Kadi, F

    2007-01-01

    In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men...... and women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross.......15+/-0.06; mean+/-SD) and females (from 0.11+/-0.04 to 0.13+/-0.05). These results suggest that 12 weeks of resistance training is effective in enhancing the satellite cell pool in skeletal muscle in the elderly....

  4. Effect of copper nanoparticles administered in ovo on the activity of proliferating cells and on the resistance of femoral bones in broiler chickens

    DEFF Research Database (Denmark)

    Mroczek-Sosnowska, Natalia; Lukasiewicz, Monika; Adamek, Dobrochna

    2017-01-01

    The objective of this study was to evaluate bone resistance after in ovo administration of copper nanoparticles (NanoCu) and to determine the number of cells positive for proliferating cell nuclear antigen (PCNA) in the femoral bones of broiler chickens (n = 12 per group). The study demonstrated...... that femoral bones from the NanoCu group were characterised by a higher weight and volume and by significantly greater resistance to fractures compared to the Control group. NanoCu promoted the proliferation of PCNA-positive cells in the long bones of chickens. A significantly higher number of PCNA...

  5. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jilu [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Mao, Daqing, E-mail: mao@tju.edu.cn [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China); Mu, Quanhua [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Luo, Yi, E-mail: luoy@nankai.edu.cn [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China)

    2015-09-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10{sup 3} to (3.68 ± 0.27) × 10{sup 6} copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10{sup 7} to (4.30 ± 0.81) × 10{sup 10} copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7

  6. Sustainable, heat-resistant and flame-retardant cellulose-based composite separator for high-performance lithium ion battery

    National Research Council Canada - National Science Library

    Zhang, Jianjun; Yue, Liping; Kong, Qingshan; Liu, Zhihong; Zhou, Xinhong; Zhang, Chuanjian; Xu, Quan; Zhang, Bo; Ding, Guoliang; Qin, Bingsheng; Duan, Yulong; Wang, Qingfu; Yao, Jianhua; Cui, Guanglei; Chen, Liquan

    2014-01-01

    A sustainable, heat-resistant and flame-retardant cellulose-based composite nonwoven has been successfully fabricated and explored its potential application for promising separator of high-performance...

  7. Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance

    DEFF Research Database (Denmark)

    Schuster, H.; Fagerberg, B.; Edwards, S.

    2008-01-01

    Aim: To determine the effects of the peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist tesaglitazar on serum levels of apolipoprotein (apo) A-I, apoB, and apoCIII in non-diabetic insulin-resistant subjects. Methods: This randomized, double-blind, multicentre, placebo...... associated with insulin resistance. (C) 2007 Elsevier Ireland Ltd. All rights reserved Udgivelsesdato: 2008/3...

  8. Plant defense against herbivorous pests: exploiting resistance and tolerance traits for sustainable crop protection

    Directory of Open Access Journals (Sweden)

    Carolyn Mitchell

    2016-07-01

    Full Text Available Interactions between plants and insect herbivores are important determinants of plant productivity in managed and natural vegetation. In response to attack, plants have evolved a range of defenses to reduce the threat of injury and loss of productivity. Crop losses from damage caused by arthropod pests can exceed 15% annually. Crop domestication and selection for improved yield and quality can alter the defensive capability of the crop, increasing reliance on artificial crop protection. Sustainable agriculture, however, depends on reduced chemical inputs. There is an urgent need, therefore, to identify plant defensive traits for crop improvement. Plant defense can be divided into resistance and tolerance strategies. Plant traits that confer herbivore resistance typically prevent or reduce herbivore damage through expression of traits that deter pests from settling, attaching to surfaces, feeding and reproducing, or that reduce palatability. Plant tolerance of herbivory involves expression of traits that limit the negative impact of herbivore damage on productivity and yield. Identifying the defensive traits expressed by plants to deter herbivores or limit herbivore damage, and understanding the underlying defense mechanisms, is crucial for crop scientists to exploit plant defensive traits in crop breeding. In this review, we assess the traits and mechanisms underpinning herbivore resistance and tolerance, and conclude that physical defense traits, plant vigor and herbivore-induced plant volatiles show considerable utility in pest control, along with mixed species crops. We highlight emerging approaches for accelerating the identification of plant defensive traits and facilitating their deployment to improve the future sustainability of crop protection.

  9. Peroxisome proliferator-activated receptor alpha improves pancreatic adaptation to insulin resistance in obese mice and reduces lipotoxicity in human islets

    NARCIS (Netherlands)

    Lalloyer, Fanny; Vandewalle, Brigitte; Percevault, Frederic; Torpier, Gerard; Kerr-Conte, Julie; Oosterveer, Maaike; Paumelle, Rejane; Fruchart, Jean-Charles; Kuipers, Folkert; Pattou, Francois; Fievet, Catherine; Staels, Bart

    Peroxisome proliferator-activated receptor (PPAR) alpha is a transcription factor controlling lipid and glucose homeostasis. PPAR alpha-deficient (-/-) mice are protected from high-fat diet-induced insulin resistance. However, the impact of PPAR alpha in the pathophysiological setting of

  10. Changes in expression of oestrogen regulated and proliferation genes with neoadjuvant treatment highlight heterogeneity of clinical resistance to the aromatase inhibitor, letrozole.

    Science.gov (United States)

    Miller, William R; Larionov, Alexey

    2010-01-01

    Clinical resistance is a major factor limiting benefits to endocrine therapy. Causes of resistance may be diverse and the mechanism of resistance in individual breast cancers is usually unknown. The present study illustrates how changes in the expression of proliferation and oestrogen-regulated genes occurring during neoadjuvant treatment with the aromatase inhibitor, letrozole, may define distinctive tumour subgroups and suggest different mechanisms of resistance in clinically endocrine resistant breast cancers. Postmenopausal women with large primary oestrogen-receptor (ER)-rich breast cancers were treated neoadjuvantly with letrozole (2.5 mg daily) for three months. Clinical response was determined by ultrasound changes in tumour volume. Tumour ribonucleic acid (RNA) from biopsies taken before, after 14 days and after three months of treatment was hybridized on Affymetrix U133A chips. Changes in expression of KIAA0101, TFF3, SERPINA3, IRS-1 and TFF1 were taken as markers of oestrogen regulation and those in CDC2, CKS-2, Cyclin B1, Thymidine Synthetase and PCNA as markers of proliferation. Fifteen tumours with < 50% volume reduction over three months of treatment were classified as being clinically non-responsive. Gene expression changes after 14 days of treatment with letrozole revealed different patterns of change in oestrogen regulated and proliferation genes in individual resistant tumours. Tumours could be separated into three different subgroups as follows: i) nine cases in which both proliferation and oestrogen signalling signatures were generally reduced on treatment (ii) four cases in which both signatures were generally unaffected or increased with treatment and (iii) two cases in which expression of the majority of oestrogen-regulated genes decreased whereas proliferation genes remained unchanged or increased. In 14 out of 15 tumours, RNA profiles were also available after three months of treatment. Patterns of change observed after 14 days were

  11. CNT1 expression influences proliferation and chemosensitivity in drug-resistant pancreatic cancer cells

    Science.gov (United States)

    Bhutia, Yangzom D.; Hung, Sau Wai; Patel, Bhavi; Lovin, Dylan; Govindarajan, Rajgopal

    2011-01-01

    Overcoming the inherent chemoresistance of pancreatic cancers remains a major goal of therapeutic investigations in this disease. In this study, we discovered a role for the human concentrative nucleoside transporter-1 (hCNT1; SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug used presently as a standard of care. Compared with normal pancreas and pancreatic ductal epithelial cells, hCNT1 expression was frequently reduced in pancreatic tumors and tumor cell lines. In addition, hCNT1-mediated 3H-gemcitabine transport was lower in pancreatic cancer cell lines and correlated with cytotoxic IC50 estimations of gemcitabine. In contrast to gemcitabine-sensitive pancreatic cancer cell lines, MIA PaCa-2, a gemcitabine-resistant pancreatic cancer cell line exhibited relatively restrictive, cell cycle-dependent hCNT1 expression and transport. hCNT1 translation was suppressed in the late G1-enriched MIA PaCa-2 cell population possibly in an miRNA-dependent manner, which corresponded with the lowest hCNT1-mediated gemcitabine transport during this phase. While hCNT1 protein was induced during G1/S transition, increased hCNT1 trafficking resulted in maximal cell surface recruitment and transport-overshoot in the G2/M phase-enriched cell population. hCNT1 protein was directed predominantly to proteasomal or lysosomal degradation in S or G2/M phase MIA PaCa-2 cells, respectively. Pharmacological inhibition of hCNT1 degradation moderately increased cell surface hCNT1 expression and cellular gemcitabine transport in MIA PaCa-2 cells. Constitutive hCNT1 expression reduced clonogenic survival of MIA PaCa-2 cells and steeply augmented gemcitabine transport and chemosensitization. In addition to supporting a putative tumor suppressor role for hCNT1, our findings identify hCNT1 as a potential candidate to render drug-resistant pancreatic cancer cells amenable to chemotherapy. PMID

  12. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hee-Jin [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of); Kim, Gwangil [Department of Pathology, CHA Bundang Medical Center, CHA University, Seoul (Korea, Republic of); Park, Kyung-Soon, E-mail: kspark@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of)

    2013-08-09

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway.

  13. Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.

    Science.gov (United States)

    Liu, Jianming; Burkin, Dean J; Kaufman, Stephen J

    2008-02-01

    The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The alpha(7)beta(1)-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of alpha(7)-integrin levels alleviates pathology in mdx/utrn(-/-) mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing alpha(7)-integrin levels affects transcription and cellular functions, we generated alpha(7)-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of alpha(7)-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy.

  14. Revision of Sustainable Criteria of Concrete Walls for Earthquake-Resistant Housing

    Directory of Open Access Journals (Sweden)

    Alcocer S.M.

    2012-10-01

    Full Text Available The seismic performance of low-rise housing has been noticeably inadequate during the most recent earthquakes occurred in Latin American countries. Moreover, the literature review revealed that some traditional techniques do not contribute to building sustainable housing. In the last decade, construction of concrete walls housing has become a preferred choice because of the speed of construction and availability of materials in most of these countries. Aimed at improving seismic design methods for this type of construction, an extensive analytical and experimental program was carried out. The experimental program included quasi-static and shaking-table tests of 47 walls with different height-to-length ratios and walls with openings. Variables studied were type of concrete, web steel ratio and type of web reinforcement. The paper presents and discusses the main results of the research program and evaluates the technical and environmental feasibility for using concrete walls for sustainable and earthquake-resistant housing. Performance of concrete walls housing is assessed in terms of key environmental and earthquake-resistant requirements. It was found that concrete wall housing is not only safe under earthquakes and easily adaptable to climate, but also it stimulates environmental conservation and promotes reducing the costs of construction, operation and maintenance.

  15. PIK3CA-mutated melanoma cells rely on cooperative signaling through mTORC1/2 for sustained proliferation.

    Science.gov (United States)

    Silva, Jillian M; Deuker, Marian M; Baguley, Bruce C; McMahon, Martin

    2017-05-01

    Malignant conversion of BRAF- or NRAS-mutated melanocytes into melanoma cells can be promoted by PI3'-lipid signaling. However, the mechanism by which PI3'-lipid signaling cooperates with mutationally activated BRAF or NRAS has not been adequately explored. Using human NRAS- or BRAF-mutated melanoma cells that co-express mutationally activated PIK3CA, we explored the contribution of PI3'-lipid signaling to cell proliferation. Despite mutational activation of PIK3CA, melanoma cells were more sensitive to the biochemical and antiproliferative effects of broader spectrum PI3K inhibitors than to an α-selective PI3K inhibitor. Combined pharmacological inhibition of MEK1/2 and PI3K signaling elicited more potent antiproliferative effects and greater inhibition of the cell division cycle compared to single-agent inhibition of either pathway alone. Analysis of signaling downstream of MEK1/2 or PI3K revealed that these pathways cooperate to regulate cell proliferation through mTORC1-mediated effects on ribosomal protein S6 and 4E-BP1 phosphorylation in an AKT-dependent manner. Although PI3K inhibition resulted in cytostatic effects on xenografted NRASQ61H /PIK3CAH1047R melanoma, combined inhibition of MEK1/2 plus PI3K elicited significant melanoma regression. This study provides insights as to how mutationally activated PIK3CA acts in concert with MEK1/2 signaling to cooperatively regulate mTORC1/2 to sustain PIK3CA-mutated melanoma proliferation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Resilience versus Resistance: Affectively Modulating Contemporary Diagrams of Social Resilience, Social Sustainability, and Social Innovation

    Directory of Open Access Journals (Sweden)

    Petra Hroch

    2013-11-01

    Full Text Available This article critically interrogates the twin notions of social sustainability and activities grouped under the term social innovation in order to argue that sustainability and innovation are schizoid modes of representing what Deleuze calls “the cliché” (the authority of the same as “the new” (difference that short-circuit any real possibility of social transformation. I argue that the kinds of solutions presented by social innovation to the problems of social sustainability in the context of a neoliberal governmentality are sustainable only in the sense that they are a model for a more collective mode of existence in an individualized realm that reciprocally supports a realm in which collective responsibility is individualized. In other words, this neo-liberal diagram catches and captures creative energies in service to the status quo. To illustrate these ideas I turn to Dutch filmmaker Bregtje van der Haak’s 2010 documentary, California Dreaming, in which she compares the popular response to the 2008 financial crisis by focusing on several families across the transatlantic transcontinental divide. She interviews Europeans who blame the state as the source of the economic problem, and thus expect the state to fix it. And she interviews Americans who, reflecting on the “American dream,” reveal their faith in meritocracy, blame themselves, and thus look to their own families and communities for solutions. Their respective stories tell us how different neo-liberal diagrams structure and modulate subjectivity and its relation to the social, as well as the emerging ways in which this relation is being framed. If, as Deleuze writes, “there is no diagram that does not also include, besides the points which it connects up, certain relatively free points, points of creativity, change and resistance,” how can analysis of these shifty subjective-social structures point us to points of resistance" (Foucault? And why is it crucial that

  17. [Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

    Science.gov (United States)

    Lin, Juan-Na; Kuang, Qiao-Ting; Ye, Kai-He; Ye, Chun-Ling; Huang, Yi; Zhang, Xiao-Qi; Ye, Wen-Cai

    2013-08-01

    To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P 0.05). Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

  18. IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Yanhan [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Yan [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Qiao, Chunxia; Liu, Guijun [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhao, Qing [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Zhou, Tingting; Chen, Guojiang [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Li, Yali [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Feng, Jiannan; Li, Yan [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Qiuping, E-mail: qpzhang@whu.edu.cn [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Peng, Hui, E-mail: p_h2002@hotmail.com [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Beijing 100850 (China)

    2013-07-12

    Highlights: •We established trastuzumab-resistant cell line SKOV3/T. •SKOV3/T enhances proliferation and in vivo carcinogenesis. •IGF-1R and HER3 genes were up-regulated in SKOV3/T based on microarray analysis. •Targeting IGF-1R and/or HER3 inhibited the proliferation of SKOV3/T. •Therapies targeting IGF-1R and HER3 might be effective in ovarian cancer. -- Abstract: Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer.

  19. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  20. Altered Landscapes and Groundwater Sustainability — Exploring Impacts with Induced Polarization, DC Resistivity, and Thermal Tracing

    Science.gov (United States)

    Eddy-Miller, C.; Caldwell, R.; Wheeler, J.; McCarthy, P.; Binley, A. M.; Constantz, J. E.; Stonestrom, D. A.

    2009-12-01

    Anthropogenically impacted landscapes constitute rising proportions of the Earth’s surface that are characterized by generally elevated nutrient and sediment loadings concurrent with increased consumptive water withdrawals. In recent years a growing number of hydraulically engineered riparian habitat restoration projects have attempted to ameliorate negative impacts of land use on groundwater-surface water systems resulting, e.g., from agricultural practices and urban development. Often the nature of groundwater-surface water interactions in pre- and minimally altered systems is poorly known, making it difficult to assess the impacts of land use and restoration projects on groundwater sustainability. Traditional assessments of surface water parameters (flow, temperature, dissolved oxygen, biotic composition, etc.) can be complemented by hydraulic and thermal measurements to better understand the important role played by groundwater-surface water interactions. Hydraulic and thermal measurements are usually limited to point samples, however, making non-invasive and spatially extensive geophysical characterizations an attractive additional tool. Groundwater-surface water interactions along the Smith River, a tributary to the Missouri River in Montana, and Fish Creek and Flat Creek, tributaries to the Snake River in Wyoming, are being examined using a combination of hydraulic measurements, thermal tracing, and electrical-property imaging. Ninety-two direct-current (DC) resistivity and induced polarization cross sections were obtained at stream transects covering a wide variety of hydrogeologic settings ranging from shallow bedrock to thick alluvial sequences, nature of groundwater-surface water interactions (always gaining, always losing, or seasonally varying) and anthropogenic impacts (minimal low-intensity agriculture to major landscape engineering, including channel reconstruction). DC resistivity and induced polarization delineated mutually distinct features

  1. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  2. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  3. Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype.

    Science.gov (United States)

    Amaral, Leonard; Spengler, Gabriella; Molnar, Joseph

    2016-11-01

    The focus of this mini-review is to identify non-toxic compounds isolated from natural sources (plants) that exhibit specific activity against efflux pumps of specific multidrug-resistant (MDR) cancer cell lines, inhibit proliferation of the MDR cancer cell lines and inhibit the activity of overexpressed efflux pumps of the MDR cancer cell line. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Paulin Roxane

    2011-09-01

    Full Text Available Background Pulmonary arterial hypertension (PAH is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis and the upregulation of growth factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET-1 promoting PASMC proliferation. Krüppel-like factor 5 (KLF5, is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation, proliferation, migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the implication of KLF5 in pulmonary arterial hypertension (PAH remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis. Methods and results We showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5 promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers survivin expression hyperpolarizing mitochondria membrane potential decreasing PASMC ability to undergo apoptosis. Conclusion We demonstrated for the first time that KLF5 is activated in human PAH and implicated in the pro-proliferative and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our findings will open new avenues of investigation on the role of KLF5 in PAH and might lead to the

  5. LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

    Science.gov (United States)

    Fang, Zheng; Zhao, Junfang; Xie, Weihong; Sun, Qiang; Wang, Haibin; Qiao, Bin

    2017-12-01

    Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR-184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR-184 to repress its expression. Rescue experiments suggested that downregulation of miR-184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP-resistant OSCC cells. Moreover, UCA1 could perform as a miR-184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP-mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  7. Mouse C2 myoblast cells resist HVJ (Sendai virus)-mediated cell fusion in the proliferating stage but become capable of fusion after differentiation.

    Science.gov (United States)

    Hirayama, E; Nakanishi, M; Honda, N; Kim, J

    1999-05-01

    To investigate the mechanism of myoblast fusion, we attempted to prepare artificial myotubes of mouse C2 myoblast cells using the hemagglutinating virus of Japan (HVJ, Sendai virus). Proliferating C2 cells showed strong resistance to HVJ-mediated cell fusion and remained morphologically unchanged even though massive numbers of virions adsorbed onto their surface. They showed no membrane disruption, which occurs in the early stage of cell fusion induced by HVJ. These observations suggest that proliferating C2 cells are resistant to HVJ-mediated cell fusion. However, upon induction of differentiation, C2 cells gradually became capable of fusion induced by HVJ and then even generated heterokaryons with Ehrlich ascites tumor cells. When differentiated C2 cells that had become fusion-sensitive were treated with HVJ in the presence of EDTA, they did not fuse but degenerated, suggesting that their cell membranes were transiently disrupted by interaction with HVJ. These results suggest that the cell membranes of myoblasts change to a fusion-capable state during the process of differentiation.

  8. Peroxisome Proliferator-Activated Receptors in Regulation of Cytochromes P450: New Way to Overcome Multidrug Resistance?

    OpenAIRE

    Katerina Cizkova; Anna Konieczna; Bela Erdosova; Radka Lichnovska; Jiri Ehrmann

    2012-01-01

    Embryonic and tumour cells are able to protect themselves against various harmful compounds. In human pathology, this phenomenon exists in the form of multidrug resistance (MDR) that significantly deteriorates success of anticancer treatment. Cytochromes P450 (CYPs) play one of the key roles in the xenobiotic metabolism. CYP expression could contribute to resistance of cancer cells to chemotherapy. CYP epoxygenases (CYP2C and CYP2J) metabolize about 20% of clinically important drugs. Besides ...

  9. Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani.

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    Sanchita Das

    Full Text Available Sodium antimony gluconate (SAG unresponsiveness of Leishmania donovani (Ld had effectively compromised the chemotherapeutic potential of SAG. 60s ribosomal L23a (60sRL23a, identified as one of the over-expressed protein in different resistant strains of L.donovani as observed with differential proteomics studies indicates towards its possible involvement in SAG resistance in L.donovani. In the present study 60sRL23a has been characterized for its probable association with SAG resistance mechanism.The expression profile of 60s ribosomal L23a (60sRL23a was checked in different SAG resistant as well as sensitive strains of L.donovani clinical isolates by real-time PCR and western blotting and was found to be up-regulated in resistant strains. Ld60sRL23a was cloned, expressed in E.coli system and purified for raising antibody in swiss mice and was observed to have cytosolic localization in L.donovani. 60sRL23a was further over-expressed in sensitive strain of L.donovani to check its sensitivity profile against SAG (Sb V and III and was found to be altered towards the resistant mode.This study reports for the first time that the over expression of 60sRL23a in SAG sensitive parasite decreases the sensitivity of the parasite towards SAG, miltefosine and paramomycin. Growth curve of the tranfectants further indicated the proliferative potential of 60sRL23a assisting the parasite survival and reaffirming the extra ribosomal role of 60sRL23a. The study thus indicates towards the role of the protein in lowering and redistributing the drug pressure by increased proliferation of parasites and warrants further longitudinal study to understand the underlying mechanism.

  10. CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

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    Hassen Kared

    Full Text Available Hepatitis C virus (HCV infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR (n = 9 and patients who achieved sustained virologic response (SVR (n = 19. We examined the expression of activation (CD38, HLA-DR, functional (CD127 and exhaustion markers (PD1, Tim-3, CD160 and CD244 on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.

  11. PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

    Science.gov (United States)

    Sato, Daisuke; Oda, Kanako; Kusunoki, Masataka; Nishina, Atsuyoshi; Takahashi, Kazuaki; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2016-02-15

    It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

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    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China); Wang, Yuchan, E-mail: wangyuchannt@126.com [Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China)

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  13. Study of the Raveling Resistance of Porous Asphalt Pavements Used in Sustainable Drainage Systems Affected by Hydrocarbon Spills

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    Jorge Rodriguez-Hernandez

    2015-12-01

    Full Text Available Permeable pavements are one of the most commonly-used sustainable drainage systems (SuDS in urban areas for managing stormwater runoff problems. Porous asphalt is widely used in surface layers of permeable pavement systems, where it can suffer from accidental oil spills from vehicles. Oil spills affect bituminous mixes through the solvent action of the hydrocarbons on the bitumen, reducing the raveling resistance of asphalt pavements. In order to assess the raveling resistance in porous asphalt pavements, the Cantabro abrasion test was performed on 200 test samples after applying controlled oil spills. Three different types of binders were used: conventional bitumen, polymer-modified bitumen and special fuel-resistant bitumen. After analyzing the results, it was concluded that the most suitable bitumen to protect against oil leakages is the polymer-modified one, which is far better than the other two types of bitumen tested.

  14. Hyperactivity, startle reactivity and cell-proliferation deficits are resistant to chronic lithium treatment in adult Nr2e1(frc/frc) mice.

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    Wong, B K Y; Hossain, S M; Trinh, E; Ottmann, G A; Budaghzadeh, S; Zheng, Q Y; Simpson, E M

    2010-10-01

    The NR2E1 region on Chromosome 6q21-22 has been repeatedly linked to bipolar disorder (BP) and NR2E1 has been associated with BP, and more specifically bipolar I disorder (BPI). In addition, patient sequencing has shown an enrichment of rare candidate-regulatory variants. Interestingly, mice carrying either spontaneous (Nr2e1(frc) ) or targeted (Tlx(-) ) deletions of Nr2e1 (here collectively known as Nr2e1-null) show similar neurological and behavioral anomalies, including hypoplasia of the cerebrum, reduced neural stem cell proliferation, extreme aggression and deficits in fear conditioning; these are the traits that have been observed in some patients with BP. Thus, NR2E1 is a positional and functional candidate for a role in BP. However, no Nr2e1-null mice have been fully evaluated for behaviors used to model BP in rodents or pharmacological responses to drugs effective in treating BP symptoms. In this study we examine Nr2e1(frc/frc) mice, homozygous for the spontaneous deletion, for abnormalities in activity, learning and information processing, and cell proliferation; these are the phenotypes that are either affected in patients with BP or commonly assessed in rodent models of BP. The effect of lithium, a drug used to treat BP, was also evaluated for its ability to attenuate Nr2e1(frc/frc) behavioral and neural stem cell-proliferation phenotypes. We show for the first time that Nr2e1-null mice exhibit extreme hyperactivity in the open field as early as postnatal day 18 and in the home cage, deficits in open-field habituation and passive avoidance, and surprisingly, an absence of acoustic startle. We observed a reduction in neural stem/progenitor cell proliferation in Nr2e1(frc/frc) mice, similar to that seen in other Nr2e1-null strains. These behavioral and cell-proliferation phenotypes were resistant to chronic-adult-lithium treatment. Thus, Nr2e1(frc/frc) mice exhibit behavioral traits used to model BP in rodents, but our results do not support Nr2e1(frc

  15. Hyperactivity, startle reactivity and cell-proliferation deficits are resistant to chronic lithium treatment in adult Nr2e1frc/frc mice

    Science.gov (United States)

    Wong, Bibiana K.Y.; Hossain, Sazzad M.; Trinh, Eric; Ottmann, Glen A.; Budaghzadeh, Saeed; Zheng, Qing Y.; Simpson, Elizabeth M.

    2012-01-01

    The NR2E1 region on Chromosome 6q21-22 has been repeatedly linked to bipolar disorder (BP) and NR2E1 has been associated with BP, and more specifically bipolar I disorder (BPI). In addition, patient sequencing has revealed an enrichment of rare candidate-regulatory variants. Interestingly, mice carrying either spontaneous (Nr2e1frc) or targeted (Tlx−) deletions of Nr2e1 (here collectively known as Nr2e1-null) show similar neurological and behavioral anomalies, including: hypoplasia of the cerebrum, reduced neural stem cell proliferation, extreme aggression, and deficits in fear conditioning; traits that have been observed in some patients with BP. Thus, NR2E1 is a positional and functional candidate for a role in BP. However, no Nr2e1-null mice have been fully evaluated for behaviors used to model BP in rodents or pharmacological responses to drugs effective in treating BP symptoms. In this study we examine Nr2e1frc/frc mice, homozygous for the spontaneous deletion, for abnormalities in activity, learning and information processing, and cell proliferation; phenotypes that are either affected in patients with BP or commonly assessed in rodent models of BP. The effect of lithium, a drug used to treat BP, was also evaluated for its ability to attenuate Nr2e1frc/frc behavioral and neural stem cell proliferation phenotypes. We show for the first time that Nr2e1-null mice exhibit extreme hyperactivity in the open field as early as postnatal day 18 and in the home cage, deficits in open-field habituation and passive avoidance, and, surprisingly, an absence of acoustic startle. We observed a reduction in neural stem/progenitor cell proliferation in Nr2e1frc/frc mice, similar to that seen in other Nr2e1-null strains. These behavioral and cell-proliferation phenotypes were resistant to chronic-adult-lithium treatment. Thus, Nr2e1frc/frc mice exhibit behavioral traits used to model BP in rodents, but our results do not support Nr2e1frc/frc mice as pharmacological models for

  16. The retardation of vasculopathy induced by attenuation of insulin resistance in the corpulent JCR:LA-cp rat is reflected by decreased vascular smooth muscle cell proliferation in vivo.

    Science.gov (United States)

    Absher, P M; Schneider, D J; Baldor, L C; Russell, J C; Sobel, B E

    1999-04-01

    Proliferation in vivo of vascular smooth muscle cells occurs early in the course of atherosclerosis. Cultured smooth muscle cells (SMCs) explanted from aortas of JCR:LA-cp corpulent rats known to exhibit metabolic derangements and insulin resistance typical of type II diabetes early in life and to develop atherosclerosis later in life exhibit increased proliferation compared with SMCs from lean, normal rats. Vascular smooth muscle proliferation in vitro was found to be positively and significantly correlated with plasma insulin levels in vivo. Proliferation of aortic SMCs from JCR:LA-cp cp/cp corpulent rats cultured in vitro exhibited increased proliferation in the presence of exogenous insulin. Exercise and diet, selected as interventions designed to ameliorate the insulin resistance and hyperinsulinemia in the JCR:LA-cp cp/cp rat, effectively lowered blood insulin levels and decreased subsequent proliferation in vitro of aortic SMCs explanted from these animals. The results indicate that assessment of proliferation of vascular smooth muscle cells ex vivo may provide insight into the presence and severity of atherogenicity in association with insulin resistance in diverse species under diverse circumstances. Accordingly, with appropriate controls, it may be possible to use SMC proliferation ex vivo as a marker of the extent to which an intervention such as administration of insulin sensitizers to experimental animals and human subjects results in a change in behavior of vessel wall elements potentially indicative of amelioration of atherogenicity and detectable as judged from reduced proliferative rates of the cells ex vivo when they have been harvested from vessels exposed to a milieu in which insulin resistance has been attenuated.

  17. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Miao, Xiaobing; Wu, Yaxun; Wang, Yuchan; Zhu, Xinghua; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong; Xu, Xiaohong; He, Song

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Silencing CAPN2 Expression Inhibited Castration-Resistant Prostate Cancer Cells Proliferation and Invasion via AKT/mTOR Signal Pathway

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    Pu Li

    2017-01-01

    Full Text Available The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3 than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2 and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues. Therefore, we showed the important roles of CAPN2 in the development and progression in CRPC cells, suggesting a new therapeutic intervention for treating castration-resistant prostate cancer patients.

  19. Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs.

    Science.gov (United States)

    Zhang, Y R; Li, B; Wang, C X; Zhou, N; Qi, W; Li, X L; Wu, L Y; Wei, S F; Zhang, Y D

    2017-03-02

    We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to

  20. Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs

    Directory of Open Access Journals (Sweden)

    Y.R. Zhang

    Full Text Available We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017. In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037. Virus load and hepatitis B E antigen (HBeAg-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000. Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036. Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05. Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the

  1. MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES

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    T. M. Sokolova

    2007-01-01

    Full Text Available Abstract. Cytomegalovirus (CMV infection in diploid human fibroblasts (HF and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to be positively associated with cellular DNA synthesis. At the same time, activities of IFNβ and IFNγ genes were at the constantly low level and were not induced in DNA-synthetic phase (S-phase of the cells. Levels of IFNα mRNA synthesis are quite different for G0- vs S-phase-synchronized HF110044 cell cultures: appropriate values for dividing cells (S-phase proved to be 100-fold higher than in resting state (G0. The mode of CMV infection in resting HF-cell could be considered either as acute, or a productive one. On the contrary, proliferating cells exhibited lagging viral syntheses and delayed cell death. Arrest of CMV replication may be, to some extent, comparable with latent infectious state, being associated with high production of IFNα. Both basal and induced levels of IFNα mRNA in CMV-resistant adult human skin fibroblast cells (HSF-1608 were 10-fold higher than in human embryo lung cell line (HELF-977, which is highly sensitive to CMV. Moreover, a short-time induction of IFNγ genes was observed in resistant cells, whereas no such effect was noticed in highly sensitive cells. CMV reproduction in sensitive cell lines (HELF-977 and HELF-110044 partially inhibits IFNα mRNA transcription at the later stages of infection (24 to 48 hours. Thus, cellular resistance and control of CMV infection in diploid fibroblasts are associated predominantly with high transcription of IFNα gene, and with temporal induction of IFNγ gene. We did not reveal any participation of IFNβ genes in protection of human diploid fibroblasts from CMV.

  2. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Zheng, Z.H.; Wang, E.H. [Institute of Pathology and Pathophysiology, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Wei, M.J. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China)

    2013-12-12

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  3. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Directory of Open Access Journals (Sweden)

    L. Zhao

    2014-01-01

    Full Text Available Fanconi anemia complementation group F protein (FANCF is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  4. Exploring Reasons for the Resistance to Sustainable Management within Non-Profit Organizations

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    Claus-Heinrich Daub

    2014-05-01

    Full Text Available The numerous empirical and conceptual studies that have been conducted over recent years concerning the social responsibility of enterprises and their contributions towards sustainable development have given very little consideration to non-profit organizations (NPOs. This is surprising, because NPOs are confronted with very similar challenges to profit-orientated enterprises regarding their evolution into sustainable organizations. This paper is a preliminary conceptual study and explores the question of why the corporate social responsibility, or corporate sustainability, of NPOs has to date been both neglected by research establishments and also extensively ignored by the NPOs during their day-to-day practical management. The example of church and pastoral institutions in Germany is used to demonstrate the extent to which they take account of ecological and social aspects in their management systems and processes and, thus, implement sustainable management within their day-to-day practice. The paper concludes with some proposals for further empirical and conceptual research projects, which are designed to analyze developments within NPOs with relation to the integration of sustainability into their management systems and processes.

  5. Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells.

    Science.gov (United States)

    Kim, Soyoung; Kim, Kyung-Chan; Lee, ChuHee

    2017-12-01

    found to be induced and reduced by VAE treatment, respectively. Taken together, our data provide that VAE targets Axl to suppress cell proliferation and to circumvent cisplatin- and erlotinib-resistance in NSCLC cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Durable resistance: a key to sustainable management of pathogens and pests.

    Science.gov (United States)

    Mundt, Christopher C

    2014-10-01

    This review briefly addresses what has been learned about resistance durability in recent years, as well as the questions that still remain. Molecular analyses of major gene interactions have potential to contribute to both breeding for resistance and improved understanding of virulence impacts on pathogen fitness. Though the molecular basis of quantitative resistance is less clear, substantial evidence has accumulated for the relative simplicity of inheritance. There is increasing evidence for specific interactions with quantitative resistance, though implications of this for durability are still unknown. Mechanisms by which resistance gene pyramids contribute to durability remain elusive, though ideas have been generated for identifying gene combinations that may be more durable. Though cultivar mixtures and related approaches have been used successfully, identifying the diseases and conditions that are most conducive to the use of diversity has been surprisingly difficult, and the selective influence of diversity on pathogen populations is complex. The importance of considering resistance durability in a landscape context has received increasing emphasis and is an important future area of research. Experimental systems are being developed to test resistance gene deployment strategies that previously could be addressed only with logic and observation. The value of molecular markers for identifying and pyramiding major genes is quite clear, but the successful use of quantitative trait loci (QTL) for marker-assisted selection of quantitative resistance will depend greatly on the degree to which the identified QTL are expressed in different genetic backgrounds. Transgenic approaches will likely provide opportunities for control of some recalcitrant pathogens, though issues of durability for transgenes are likely to be no different than other genes for resistance. The need for high quality phenotypic analysis and screening methodologies is a priority, and field

  7. Sustained complete remission in a patient with platinum-resistant ovarian yolk sac tumor.

    Science.gov (United States)

    Jeyakumar, A; Chalas, E; Hindenburg, A

    2001-09-01

    Yolk sac tumors of the ovary are generally very responsive to chemotherapy; however, they are difficult to manage in the setting of platinum resistance where treatment options are limited and outcomes are poorer. We present a 39-year-old woman who had a platinum-resistant yolk sac ovarian tumor. She achieved complete remission on an innovative regimen of docetaxel, gemcitabine, and thalidomide. The combination of docetaxel, gemcitabine, and thalidomide might be an active regimen for platinum-resistant ovarian nondysgerminomas and further investigation of this combination is warranted. Copyright 2001 Academic Press.

  8. Environmental enrichment induces behavioral recovery and enhanced hippocampal cell proliferation in an antidepressant-resistant animal model for PTSD.

    Directory of Open Access Journals (Sweden)

    Hendrikus Hendriksen

    Full Text Available BACKGROUND: Post traumatic stress disorder (PTSD can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS. METHODOLOGY/PRINCIPAL FINDINGS: IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE. This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus. CONCLUSIONS/SIGNIFICANCE: This animal study shows the importance of (physical exercise in the treatment of psychiatric diseases, including post-traumatic stress disorder and points out the possible role of EE in studying the mechanism of recovery from anxiety disorders.

  9. The colony-stimulating factor-1 (CSF-1 receptor sustains ERK1/2 activation and proliferation in breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Andrea Morandi

    Full Text Available Breast cancer is the second leading cause of cancer-related deaths in western countries. Colony-Stimulating Factor-1 (CSF-1 and its receptor (CSF-1R regulate macrophage and osteoclast production, trophoblast implantation and mammary gland development. The expression of CSF-1R and/or CSF-1 strongly correlates with poor prognosis in several human epithelial tumors, including breast carcinomas. We demonstrate that CSF-1 and CSF-1R are expressed, although at different levels, in 16/17 breast cancer cell lines tested with no differences among molecular subtypes. The role of CSF-1/CSF-1R in the proliferation of breast cancer cells was then studied in MDAMB468 and SKBR3 cells belonging to different subtypes. CSF-1 administration induced ERK1/2 phosphorylation and enhanced cell proliferation in both cell lines. Furthermore, the inhibition of CSF-1/CSF-1R signaling, by CSF-1R siRNA or imatinib treatment, impaired CSF-1 induced ERK1/2 activation and cell proliferation. We also demonstrate that c-Jun, cyclin D1 and c-Myc, known for their involvement in cell proliferation, are downstream CSF-1R in breast cancer cells. The presence of a proliferative CSF-1/CSF-1R autocrine loop involving ERK1/2 was also found. The wide expression of the CSF-1/CSF-1R pair across breast cancer cell subtypes supports CSF-1/CSF-1R targeting in breast cancer therapy.

  10. Sustaining global agriculture through rapid detection and deployment of genetic resistance to deadly crop diseases.

    Science.gov (United States)

    Periyannan, Sambasivam

    2017-12-04

    Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Genetically encoded resistance is a major component of crop disease management. Historically, gene loci conferring resistance to pathogens have been identified through classical genetic methods. In recent years, accelerated gene cloning strategies have become available through advances in sequencing, gene capture and strategies for reducing genome complexity. Here, I describe these approaches with key emphasis on the isolation of resistance genes to the cereal crop diseases that are an ongoing threat to global food security. Rapid gene isolation enables their efficient deployment through marker-assisted selection and transgenic technology. Together with innovations in genome editing and progress in pathogen virulence studies, this creates further opportunities to engineer long-lasting resistance. These approaches will speed progress towards a future of farming using fewer pesticides. © 2017 Commonwealth of Australia. New Phytologist © 2017 New Phytologist Trust.

  11. pH-dependent effects of 2,4-dinitrophenol (DNP) on proliferation, endocytosis, fine structure and DNP resistance in Tetrahymena

    DEFF Research Database (Denmark)

    Nilsson, Jytte R.

    1995-01-01

    Biologi, 2,4-dinitrophenol, pH-dependence, fine structure, cell proliferation, phagocytosis, Tetrahymena pyriformis......Biologi, 2,4-dinitrophenol, pH-dependence, fine structure, cell proliferation, phagocytosis, Tetrahymena pyriformis...

  12. Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

    Science.gov (United States)

    Laurito, Marcela Pezzoto; Parise, Edison Roberto

    2013-01-01

    Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  13. Resistant carbohydrates stimulate cell proliferation and crypt fission in wild-type mice and in the Apc(Min/+) mouse model of intestinal cancer, association with enhanced polyp development.

    Science.gov (United States)

    Mandir, Nikki; Englyst, Hans; Goodlad, Robert A

    2008-10-01

    Fermentation of carbohydrates in the colon can stimulate cell proliferation and could thus be a cancer risk. The effects of resistant carbohydrates, i.e. those not digested and absorbed in the small intestine, on cell proliferation, crypt fission and polyp development were investigated in wild-type and adenomatous polyposis coli multiple intestinal neoplasia (Apc(Min/+)) mice. Fifteen 4-week-old female wild-type and fifteen Apc(Min/+) mice were used for each group and fed a chow diet, a semi-synthetic diet or the semi-synthetic supplemented with wheat bran or an apple pomace preparation, both high in resistant carbohydrates, for 8 weeks. Tissue from all mice was used to measure cell proliferation and crypt fission and tissue from the Apc(Min/+) mice was scored for polyp number and tumour burden. There were slight reductions in intestinal mass in the mice fed the semi-synthetic diets and this was increased by the inclusion of resistant carbohydrates. The Apc(Min/+) mice had elevated cell proliferation and crypt fission in the distal small intestine and colon and these were increased by the resistant carbohydrates. Bran or apple pomace significantly increased polyp number in the proximal third of the small intestine. Apple pulp more than doubled polyp number throughout the small bowel (99.2 (SEM 11.1) v. 40.0 (SEM 8.2), Ptypes of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission.

  14. Environmental and Sustainable Technology Evaluation: Mold-Resistant Armacell Insulation--Armacell LLC, AP Armaflex Black

    Science.gov (United States)

    The ESTE test program measured the mold resistance of Armacell AP Armaflex Black insulation. Tests for emissions of VOCs and formaldehyde were also performed. AP Armaflex Roll Insulation is a black flexible closed-cell, fiber-free elastomeric thermal insulation. The expanded clos...

  15. Environmental and Sustainable Technology Evaluation: Mold-resistant Lonseal flooring--Lonseal, Inc., Lonwood Natural

    Science.gov (United States)

    The test program measured the mold resistance of Lonseal Lonwood Natural flooring. One additional ancillary test for emissions of VOCs and formaldehyde was performed. Lonwood Natural flooring is a sheet vinyl product with an embossed wood-grain texture. Constructed in multiple la...

  16. Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells.

    Science.gov (United States)

    Sauer, Scott J; Tarpley, Michael; Shah, Imran; Save, Akshay V; Lyerly, H Kim; Patierno, Steven R; Williams, Kevin P; Devi, Gayathri R

    2017-03-01

    Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to induce oxidative stress resulting in perturbations in signal transduction pathways. It is therefore of interest to identify chemicals that can potentiate EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a subset of chemicals from the EPA ToxCast set for their effect on EGFR activation and in multiple cancer phenotypic assays. We demonstrated that endocrine-disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and tumor spheroid formation in vitro, reflecting IBC-specific pathological characteristics. Furthermore, we identified that BPA was able to attenuate the inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent growth assay. These findings provide a potential mechanistic basis for environmental chemicals such as BPA in potentiating a hyperproliferative and death-resistant phenotype in cancer cells by activating mitogenic pathways to which the tumor cells are addicted for survival. © The Author 2017. Published by Oxford University Press. All rights reserved. For

  17. Blueberry intake alters skeletal muscle and adipose tissue peroxisome proliferator-activated receptor activity and reduces insulin resistance in obese rats.

    Science.gov (United States)

    Seymour, E Mitchell; Tanone, Ignasia I; Urcuyo-Llanes, Daniel E; Lewis, Sarah K; Kirakosyan, Ara; Kondoleon, Michael G; Kaufman, Peter B; Bolling, Steven F

    2011-12-01

    Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.

  18. Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase 1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin Resistance of Lung Cancer Cells.

    Science.gov (United States)

    Endo, Satoshi; Xia, Shuang; Suyama, Miho; Morikawa, Yoshifumi; Oguri, Hiroaki; Hu, Dawei; Ao, Yoshinori; Takahara, Satoyuki; Horino, Yoshikazu; Hayakawa, Yoshihiro; Watanabe, Yurie; Gouda, Hiroaki; Hara, Akira; Kuwata, Kazuo; Toyooka, Naoki; Matsunaga, Toshiyuki; Ikari, Akira

    2017-10-26

    Aldo-keto reductase 1B10 (AKR1B10) is overexpressed in several extraintestinal cancers, particularly in non-small-cell lung cancer, where AKR1B10 is a potential diagnostic marker and therapeutic target. Selective AKR1B10 inhibitors are required because compounds should not inhibit the highly related aldose reductase that is involved in monosaccharide and prostaglandin metabolism. Currently, 7-hydroxy-2-(4-methoxyphenylimino)-2H-chromene-3-carboxylic acid benzylamide (HMPC) is known to be the most potent competitive inhibitor of AKR1B10, but it is nonselective. In this study, derivatives of HMPC were synthesized by removing the 4-methoxyphenylimino moiety and replacing the benzylamide with phenylpropylamide. Among them, 4c and 4e showed higher AKR1B10 inhibitory potency (IC50 4.2 and 3.5 nM, respectively) and selectivity than HMPC. The treatments with the two compounds significantly suppressed not only migration, proliferation, and metastasis of lung cancer A549 cells but also metastatic and invasive potentials of cisplatin-resistant A549 cells.

  19. Candesartan cilexetil prevents diet-induced insulin resistance via peroxisome proliferator-activated receptor-γ activation in an obese rat model.

    Science.gov (United States)

    Yan, Wen-Hua; Pan, Chang-Yu; Dou, Jing-Tao; Meng, Jun-Hua; Wang, Bao-An; Mu, Yi-Ming

    2016-07-01

    Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.

  20. Peroxisome Proliferator-Activated Receptor α Activates Human Multidrug Resistance Transporter 3/ATP-Binding Cassette Protein Subfamily B4 Transcription and Increases Rat Biliary Phosphatidylcholine Secretion

    Science.gov (United States)

    Ghonem, Nisanne S.; Ananthanarayanan, Meenakshisundaram; Soroka, Carol J.; Boyer, James L.

    2014-01-01

    Multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 (MDR3/ABCB4) is a critical determinant of biliary phosphatidylcholine (PC) secretion. Clinically, mutations and partial deficiencies in MDR3 result in cholestatic liver injury. Thus, MDR3 is a potential therapeutic target for cholestatic liver disease. Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) α ligand that has antiinflammatory actions and regulates bile acid detoxification. Here we examined the mechanism by which fenofibrate regulates MDR3 gene expression. Fenofibrate significantly up-regulated MDR3 messenger RNA (mRNA) and protein expression in primary cultured human hepatocytes, and stimulated MDR3 promoter activity in HepG2 cells. In silico analysis of 5′-upstream region of human MDR3 gene revealed a number of PPARα response elements (PPRE). Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated specific binding of PPARα to the human MDR3 promoter. Targeted mutagenesis of three novel PPREs reduced inducibility of the MDR3 promoter by fenofibrate. In collagen sandwich cultured rat hepatocytes, treatment with fenofibrate increased secretion of fluorescent PC into bile canaliculi. Conclusion Fenofibrate transactivates MDR3 gene transcription by way of the binding of PPARα to three novel and functionally critical PPREs in the MDR3 promoter. Fenofibrate treatment further stimulates biliary phosphatidylcholine secretion in rat hepatocytes, thereby providing a functional correlate. We have established a molecular mechanism that may contribute to the beneficial use of fenofibrate therapy in human cholestatic liver disease. PMID:24122873

  1. ADP-ribosylation factor 1 (ARF1) takes part in cell proliferation and cell adhesion-mediated drug resistance (CAM-DR).

    Science.gov (United States)

    Xu, Xiaohong; Wang, Qiru; He, Yunhua; Ding, Linlin; Zhong, Fei; Ou, Yangyu; Shen, Yaodong; Liu, Hong; He, Song

    2017-05-01

    Cell adhesion-mediated drug resistance (CAM-DR) remains the primary obstacle in human multiple myeloma (MM) therapy. In this study, we aimed at investigating the expression and biologic function of ARF1 in MM. We determined that ARF1 expression was positively correlated with cell proliferation and knockdown of ARF1 contributed to CAM-DR. The enhancement in the adhesion of MM cells to fibronectin (FN) or the bone marrow stroma cell line HS-5 cells translated to an increased CAM-DR phenotype. Importantly, we showed that this CAM-DR phenotype was correlated with the phosphorylation of Akt and ERK in MM cells. Moreover, we sought to determine whether ARF1 could interact with p27 in RPMI8226 cells. Knockdown of ARF1 also significantly decreased pT157-p27 protein expression in RPMI8226 cells. Our research shows ARF1 may reverse CAM-DR by regulating phosphorylation of p27 at T157 in MM. Taken together, our data shed new light on the molecular mechanism of CAM-DR in MM, and targeting ARF1 may be a novel therapeutic approach for improving the effectiveness of chemotherapy in MM.

  2. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension.

    Science.gov (United States)

    Hering, Dagmara; Marusic, Petra; Walton, Antony S; Lambert, Elisabeth A; Krum, Henry; Narkiewicz, Krzysztof; Lambert, Gavin W; Esler, Murray D; Schlaich, Markus P

    2014-07-01

    Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering effect has been demonstrated, the long-term effect on MSNA remains elusive. We investigated whether RDN influences MSNA over time. Office BP and MSNA were obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant hypertension. Office BP averaged 166±22/88±19 mm Hg, despite the use of an average of 4.8±2.1 antihypertensive drugs. Baseline MSNA was 51±11 bursts/min ≈2- to 3-fold higher than the level observed in healthy controls. Mean office systolic and diastolic BP significantly decreased by -12.6±18.3/-6.5±9.2, -16.1±25.6/-8.6±12.9, and -21.2±29.1/-11.1±12.9 mm Hg (Phypertension and high baseline MSNA. These observations are compatible with the hypothesis of a substantial contribution of afferent renal nerve signaling to increased BP in resistant hypertension and argue against a relevant reinnervation at 1 year after procedure. © 2014 American Heart Association, Inc.

  3. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.

    Science.gov (United States)

    Ding, Jane; Li, Tai; Wang, Xiangwei; Zhao, Erhu; Choi, Jeong-Hyeon; Yang, Liqun; Zha, Yunhong; Dong, Zheng; Huang, Shuang; Asara, John M; Cui, Hongjuan; Ding, Han-Fei

    2013-12-03

    Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure

    DEFF Research Database (Denmark)

    Schultze, Anna; Paredes, Roger; Sabin, Caroline

    2014-01-01

    mutations on CD4 slopes in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test...... during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log......-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. RESULTS: A total of 2731 patients experiencing a median of 1 (range 1-4) episodes were included in this analysis. The prevalence of any...

  5. Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice.

    Science.gov (United States)

    Jalabert, Audrey; Vial, Guillaume; Guay, Claudiane; Wiklander, Oscar P B; Nordin, Joel Z; Aswad, Hala; Forterre, Alexis; Meugnier, Emmanuelle; Pesenti, Sandra; Regazzi, Romano; Danty-Berger, Emmanuelle; Ducreux, Sylvie; Vidal, Hubert; El-Andaloussi, Samir; Rieusset, Jennifer; Rome, Sophie

    2016-05-01

    The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM-released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes. Mice were fed for 16 weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle. Fluorescent ELVs from HPD or SCD quadriceps were injected i.v. or intramuscularly (i.m.) into mice to determine their biodistributions. Micro (mi)RNA quantification in ELVs was determined using quantitative real-time RT-PCR (qRT-PCR)-based TaqMan low-density arrays. Microarray analyses were performed to determine whether standard diet ELVs (SD-ELVs) and high palmitate diet ELVs (HPD-ELVs) induced specific transcriptional signatures in MIN6B1 cells. In vivo, muscle ELVs were taken up by pancreas, 24 h post-injection. In vitro, both SD-ELVs and HPD-ELVs transferred proteins and miRNAs to MIN6B1 cells and modulated gene expressions whereas only HPD-ELVs induced proliferation of MIN6B1 cells and isolated islets. Bioinformatic analyses suggested that transferred HPD-ELV miRNAs may participate in these effects. To validate this, we demonstrated that miR-16, which is overexpressed in HPD-ELVs, was transferred to MIN6B1 cells and regulated Ptch1, involved in pancreas development. In vivo, islets from HPD mice showed increased size and altered expression of genes involved in development, including Ptch1, suggesting that the effect of palm oil on islet size in vivo was reproduced in vitro by treating beta cells with HPD-ELVs. Our data suggest that muscle ELVs might have an endocrine effect and could participate in adaptations in beta cell mass during insulin resistance.

  6. m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.

    Science.gov (United States)

    Zhang, Sicong; Zhao, Boxuan Simen; Zhou, Aidong; Lin, Kangyu; Zheng, Shaoping; Lu, Zhike; Chen, Yaohui; Sulman, Erik P; Xie, Keping; Bögler, Oliver; Majumder, Sadhan; He, Chuan; Huang, Suyun

    2017-04-10

    The dynamic and reversible N6-methyladenosine (m6A) RNA modification installed and erased by N6-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m6A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m6A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a critical function for ALKBH5 and provides insight into critical roles of m6A methylation in glioblastoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. In vivo and ex vivo regulation of breast cancer resistant protein (Bcrp) by peroxisome proliferator-activated receptor alpha (Pparα) at the blood-brain barrier.

    Science.gov (United States)

    Hoque, Md Tozammel; Shah, Arpit; More, Vijay; Miller, David S; Bendayan, Reina

    2015-12-01

    Breast cancer resistance protein (Bcrp/Abcg2) localized at the blood-brain barrier (BBB) limits permeability into the brain of many xenobiotics, including pharmacological agents. Peroxisome proliferator-activated receptor α (Pparα), a ligand-activated transcription factor, primarily involved in lipid metabolism, has been shown to regulate the functional expression of Bcrp in human cerebral microvascular endothelial cells (hCMEC/D3). The aim of this study was to investigate ex vivo and in vivo, the regulation of Bcrp by Pparα in an intact BBB. Ex vivo quantitative real-time PCR and immunoblot analyses showed significant up-regulation of Abcg2/Bcrp mRNA and protein levels in CD-1 mouse brain capillaries incubated with clofibrate, a Pparα ligand. Fluorescence-based transport assays in CD-1 and C57BL/6 brain capillaries showed that exposure to clofibrate significantly increased Bcrp transport activity. This increase was not observed in capillaries isolated from Pparα knockout mice. In vivo, we found: i) significant Bcrp protein up-regulation in clofibrate-dosed CD-1 and C57BL/6 capillary lysates, but no effect in Pparα knockout capillary lysates, and ii) significantly increased Bcrp transport activity in capillaries isolated from clofibrate-treated mice. These results demonstrate an increase in Bcrp functional expression by Pparα in brain capillaries, and suggest that Pparα is another nuclear receptor that can contribute to the regulation of membrane efflux transporters and drug permeability at the BBB. We propose the involvement of the following pathways in clofibrate-mediated induction of the drug transporter Abcg2/Bcrp mRNA, protein expression and function by the nuclear receptor Pparα, in mouse brain capillary endothelial cells. Upon activation with clofibrate (Pparα, ligand), Pparα complex translocates from the cytoplasm into the nucleus and further recruits coactivators and transcription machinery which induce the transcription of Abcg2 gene and

  8. Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

    Science.gov (United States)

    Crisan, Dana; Grigorescu, Mircea Dan; Radu, Corina; Suciu, Alina; Grigorescu, Mircea

    2017-04-01

    One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

  9. MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin.

    Science.gov (United States)

    Zhang, Zi-Wei; Guo, Rui-Wei; Lv, Jin-Lin; Wang, Xian-Mei; Ye, Jin-Shan; Lu, Ni-Hong; Liang, Xing; Yang, Li-Xia

    2017-04-29

    Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

    DEFF Research Database (Denmark)

    Qi, Weier; Li, Qian; Liew, Chong Wee

    2017-01-01

    as Map2k1) and increased DNA methylation of the Shp-1 promoter. VSMCs from Shp-1-Tg mice exhibited impaired platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation with a concomitant decrease in PDGF-stimulated VSMC proliferation and migration. Similarly, HFD-fed Shp-1-Tg mice and mice...

  11. CAF-derived HGF promotes cell proliferation and drug resistance by up-regulating the c-Met/PI3K/Akt and GRP78 signalling in ovarian cancer cells.

    Science.gov (United States)

    Deying, Wei; Feng, Geng; Shumei, Liang; Hui, Zhao; Ming, Liu; Hongqing, Wang

    2017-04-28

    The tumour microenvironment is a highly heterogeneous entity that plays crucial roles in cancer progression. As the most prominent stromal cell types, cancer-associated fibroblasts (CAFs) produce a variety of factors into the tumour microenvironment. In the present study, we firstly isolated CAFs from tumour tissues of the patients with ovarian cancer and demonstrated that the hepatocyte growth factor (HGF) was highly expressed in the supernatants of CAFs. CAF-derived HGF or human recombinant HGF promoted cell proliferation in human ovarian cell lines SKOV3 and HO-8910 cells. Western blotting analysis also showed that CAF-derived HGF or recombinant HGF activated c-Met/phosphoinositide 3-kinase (PI3K)/Akt and glucose-regulated protein 78 (GRP78) signalling pathways in ovarian cancer cells, and these effects could be abrogated by anti-HGF and c-Met inhibitor INCB28060. Moreover, HGF in CAF matrix attenuated paclitaxel (PAC)-caused inhibition of cell proliferation and increase in cell apoptosis through activating c-Met/PI3K/Akt and GRP78 pathways in SKOV3 and HO-8910 cells. The results in vitro were further validated in nude mice. These findings suggest that CAF-derived HGF plays crucial roles in cell proliferation and drug resistance in ovarian cancer cells. © 2017 The Author(s).

  12. Over-expression of CHAF1A promotes cell proliferation and apoptosis resistance in glioblastoma cells via AKT/FOXO3a/Bim pathway

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Honghai; Du, Bin [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Jiang, Huili [Friendship Nephrology and Blood Purification Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Gao, Jun, E-mail: gaoj1666@126.com [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China)

    2016-01-22

    Chromatinassembly factor 1 subunit A (CHAF1A) has been reported to be involved in several human diseases including cancer. However, the biological and clinical significance of CHAF1A in glioblastoma progression remains largely unknown. In this study, we found that up-regulation of CHAF1A happens frequently in glioblastoma tissues and is associated with glioblastoma prognosis. Knockout of CHAF1A by CRISPR/CAS9 technology induce G1 phase arrest and apoptosis in glioblastoma cell U251 and U87. In addition, inhibition of CHAF1A influenced the signal transduction of the AKT/FOXO3a/Bim axis, which is required for glioblastoma cell proliferation. Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma.

  13. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Pedro Escoll

    2015-01-01

    Full Text Available Clinical treatment with glucocorticoids (GC can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR, a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR- driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC. After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, GRSer203 and GRSer211 phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over ...

  15. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  16. Animation of Antimicrobial Resistance

    Science.gov (United States)

    ... Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  17. Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptornegative inflammatory breast cancer cells

    Science.gov (United States)

    Background: Inflammatory breast cancer (IBC) is a distinct and the deadliest breast cancer variant, which shows a rapid rate of progression and acquired therapeutic resistance. Epidemiological studies suggest that chemical exposure in the environment and consumer products can aff...

  18. Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells.

    Science.gov (United States)

    Wang, Yan Yan; Liu, Yao; Ni, Xiao Yan; Bai, Zhen Huan; Chen, Qiong Yun; Zhang, Ye; Gao, Feng Guang

    2014-03-01

    Although nicotine is a risk factor for carcinogenesis and atherosclerosis, epidemiological data indicate that nicotine has therapeutic benefits in treating Alzheimer's disease. Our previous studies also showed that nicotine-treated dendritic cells have potential antitumor effects. Hence, the precise effects of nicotine on the biological characterizations of cells are controversial. The aim of the present study was to assess the roles of α7 nicotinic acetylcholine receptors (nAChRs), Erk1/2-p38-JNK and PI3K-Akt pathway in nicotine-mediated proliferation and anti-apoptosis effects. The results firstly showed that nicotine treatment clearly augmented cell viability and upregulated PCNA expression in both Raw264.7 and El4 cells. Meanwhile, nicotine afforded protection against cisplatin-induced toxicity through inhibiting caspase-3 activation and upregulating anti-apoptotic protein expression. Further exploration demonstrated that nicotine efficiently abolished cisplatin-promoted mitochondria translocation of Bax and the release of cytochrome c. The pretreatment of α-bungarotoxin and tubocurarine chloride significantly attenuated nicotine-augmented cell viability, abolished caspase-3 activation and α7 nAChR upregulation. Both Erk-JNK-p38 and PI3K-Akt signaling pathways could be activated by nicotine treatment in Raw264.7 and El4 cells. Notably, when Erk-JNK and PI3K-Akt activities were inhibited, nicotine-augmented cell proliferation and anti-apoptotic effects were abolished accordingly. The results presented here indicate that nicotine could achieve α7 nAChR-mediated proliferation and anti-apoptotic effects by activating Erk-JNK and PI3K-Akt pathways respectively, providing potential therapeutic molecules to deal with smoking-associated human diseases.

  19. Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mariko Abe

    Full Text Available Internal tandem duplication (ITD mutations in the Fms-related tyrosine kinase 3 (FLT3 gene (FLT3-ITD are associated with poor prognosis in patients with acute myeloid leukemia (AML. Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3-ITD activates a novel pathway involving p21Cdkn1a (p21 and pre-B cell leukemia transcription factor 1 (Pbx1 that attenuates FLT3-ITD cell proliferation and is involved in the development of drug resistance. FLT3-ITD up-regulated p21 expression in both mouse bone marrow c-kit+-Sca-1+-Lin- (KSL cells and Ba/F3 cells. The loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of concomitantly enriching the S+G2/M phase population and significantly increasing the expression of Pbx1, but not Evi-1, in FLT3-ITD+ cells. This enhanced cell proliferation following the loss of p21 was partially abrogated when Pbx1 expression was silenced in FLT3-ITD+ primary bone marrow colony-forming cells and Ba/F3 cells. When FLT3-ITD was antagonized with AC220, a selective inhibitor of FLT3-ITD, p21 expression was decreased coincident with Pbx1 mRNA up-regulation and a rapid decline in the number of viable FLT3-ITD+ Ba/F3 cells; however, the cells eventually became refractory to AC220. Overexpressing p21 in FLT3-ITD+ Ba/F3 cells delayed the emergence of cells that were refractory to AC220, whereas p21 silencing accelerated their development. These data indicate that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression.

  20. Sustainability of water reclamation: long-term recharge with reclaimed wastewater does not enhance antibiotic resistance in sediment bacteria

    Science.gov (United States)

    Wastewater reclamation for municipal irrigation is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR) in soil bacteria after exposure to residual pharmaceuticals in reclaimed water. Thoug...

  1. Insecticide resistance in Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) and Anopheles gambiae Giles (Diptera: Culicidae) could compromise the sustainability of malaria vector control strategies in West Africa.

    Science.gov (United States)

    Gnankiné, Olivier; Bassolé, Imael H N; Chandre, Fabrice; Glitho, Isabelle; Akogbeto, Martin; Dabiré, Roch K; Martin, Thibaud

    2013-10-01

    Insecticides from the organophosphate (OP) and pyrethroid (PY) chemical families, have respectively, been in use for 50 and 30 years in West Africa, mainly against agricultural pests, but also against vectors of human disease. The selection pressure, with practically the same molecules year after year (mainly on cotton), has caused insecticide resistance in pest populations such as Bemisia tabaci, vector of harmful phytoviruses on vegetables. The evolution toward insecticide resistance in malaria vectors such as Anopheles gambiae sensus lato (s.l.) is probably related to the current use of these insecticides in agriculture. Thus, successful pest and vector control in West Africa requires an investigation of insect susceptibility, in relation to the identification of species and sub species, such as molecular forms or biotypes. Identification of knock down resistance (kdr) and acetylcholinesterase gene (Ace1) mutations modifying insecticide targets in individual insects and measure of enzymes activity typically involved in insecticide metabolism (oxidase, esterase and glutathion-S-transferase) are indispensable in understanding the mechanisms of resistance. Insecticide resistance is a good example in which genotype-phenotype links have been made successfully. Insecticides used in agriculture continue to select new resistant populations of B. tabaci that could be from different biotype vectors of plant viruses. As well, the evolution of insecticide resistance in An. gambiae threatens the management of malaria vectors in West Africa. It raises the question of priority in the use of insecticides in health and/or agriculture, and more generally, the question of sustainability of crop protection and vector control strategies in the region. Here, we review the susceptibility tests, biochemical and molecular assays data for B. tabaci, a major pest in cotton and vegetable crops, and An. gambiae, main vector of malaria. The data reviewed was collected in Benin and Burkina

  2. Sustainability of Water Reclamation: Long-Term Recharge with Reclaimed Wastewater Does Not Enhance Antibiotic Resistance in Sediment Bacteria

    Directory of Open Access Journals (Sweden)

    Jean E. McLain

    2014-03-01

    Full Text Available Wastewater reclamation for municipal irrigation is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR in environmental bacteria after exposure to residual pharmaceuticals in reclaimed water. Though scientific studies have reported high levels of AR in soils irrigated with wastewater, these works often fail to address the soil resistome, or the natural occurrence of AR. This study compared AR patterns in sediment Enterococcus isolated from water storage basins containing either reclaimed water or groundwater in central Arizona. Resistance to 16 antibiotics was quantified in isolates to a depth of 30 cm. Results reveal high levels of resistance to certain antibiotics, including lincomycin, ciprofloxacin, and erythromycin, exists in sediments regardless of the water source (groundwater, reclaimed water, and higher AR was not detectable in reclaimed water sediments. Furthermore, multiple-antibiotic-resistance (MAR was substantially reduced in isolates from reclaimed water sediments, compared to freshwater sediment isolates. Comparing the development of AR in sediment bacteria at these two sites will increase awareness of the environmental and public health impacts of using reclaimed water for irrigation of municipal areas, and illustrates the necessity for control sites in studies examining AR development in environmental microbiota.

  3. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance

    Directory of Open Access Journals (Sweden)

    Karen A. Boehme

    2018-01-01

    Full Text Available Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC.

  4. Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood-flow restriction

    DEFF Research Database (Denmark)

    Nielsen, Jakob Lindberg; Aagaard, Per; Bech, Rune Dueholm

    2012-01-01

    Low-load resistance training with blood-flow restriction has been shown to elicit substantial increases in muscle mass and muscle strength; however the effect on myogenic stem cells (MSC) and myonuclei number remains unexplored. Ten male subjects (22.8±2.3 yrs) performed 4 sets of knee extensor...... exercise (20% 1RM) to concentric failure during blood-flow restriction (BFR) of the proximal thigh (100 mmHg), while eight work-matched controls (21.9±3.0 yrs) trained without BFR (CON). 23 training sessions were performed within 19 days. Maximal isometric knee extensor strength (MVC) was examined pre...... and post training, while muscle biopsies were obtained at baseline (Pre), after 8 days intervention (Mid8) and 3 (Post3) and 10 days (Post10) post training to examine changes in myofibre area (MFA), MSC and myonuclei number. MVC increased by 7.1% (Post5) and 10.6% (Post12) (P...

  5. The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts.

    Directory of Open Access Journals (Sweden)

    Jelena Markovic

    2009-07-01

    Full Text Available Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate.We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM and buthionine sulfoximine (BSO, and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation.Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle.

  6. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will result in the development of resistant strains of bacteria, complicating clinician's efforts to select the appropriate antimicrobial ...

  7. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Medicine (CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. ... concept more understandable to non-scientists by showing how bacterial antimicrobial resistance can develop and spread. All ...

  8. Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model.

    Science.gov (United States)

    Mihu, Mircea Radu; Cabral, Vitor; Pattabhi, Rodney; Tar, Moses T; Davies, Kelvin P; Friedman, Adam J; Martinez, Luis R; Nosanchuk, Joshua D

    2017-01-01

    Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices. Copyright © 2016 American Society for Microbiology.

  9. Sustained effect of resistance training on blood pressure and hand grip strength following a detraining period in elderly hypertensive women: a pilot study.

    Science.gov (United States)

    Nascimento, Dahan da Cunha; Tibana, Ramires Alsamir; Benik, Franklin M; Fontana, Keila Elizabeth; Ribeiro Neto, Frederico; Santana, Frederico Santos de; Santos-Neto, Leopoldo; Silva, Renato André Sousa; Silva, Alessandro Oliveira; Farias, Darlan Lopes; Balsamo, Sandor; Prestes, Jonato

    2014-01-01

    Hypertension is the most prevalent modifiable risk factor with a high prevalence among older adults. Exercise is a nonpharmacological treatment shown to benefit all patients with hypertension. This study examined the effects of a 14-week moderate intensity resistance training program (RT) on the maintenance of blood pressure and hand grip strength during an extended detraining period in elderly hypertensive women. Twelve hypertensive sedentary elderly women completed 14 weeks of whole body RT at a moderate perceived exertion following a detraining period of 14 weeks. Following the training period, participants demonstrated an increase in absolute hand grip strength (P=0.001), relative hand grip strength (P=0.032) and a decrease of systolic (P=0.001), diastolic (P=0.008), and mean blood pressure (P=0.002) when compared to pre-exercise values. In addition, these effects were sustained after 14 weeks of detraining. Resistance training may be a valuable method to improve muscular strength and blood pressure in elderly people with benefits being maintained up to 14 weeks following training cessation.

  10. Diffusion of global sustainability standards

    NARCIS (Netherlands)

    Schouten, Greetje; Vellema, Sietze; Wijk, van J.

    2016-01-01

    The past two decades saw a rapid proliferation of sustainability standards created by multi-stakeholder partnerships of multinationals and international NGOs. This paper argues that the transformative capacity of these global partnerships to bring about sustainable change largely depends on how

  11. Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1alpha) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats.

    Science.gov (United States)

    Benton, C R; Holloway, G P; Han, X-X; Yoshida, Y; Snook, L A; Lally, J; Glatz, J F C; Luiken, J J F P; Chabowski, A; Bonen, A

    2010-09-01

    Reductions in peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1alpha) levels have been associated with the skeletal muscle insulin resistance. However, in vivo, the therapeutic potential of PGC-1alpha has met with failure, as supra-physiological overexpression of PGC-1alpha induced insulin resistance, due to fatty acid translocase (FAT)-mediated lipid accumulation. Based on physiological and metabolic considerations, we hypothesised that a modest increase in PGC-1alpha levels would limit FAT upregulation and improve lipid metabolism and insulin sensitivity, although these effects may differ in lean and insulin-resistant muscle. Pgc-1alpha was transfected into lean and obese Zucker rat muscles. Two weeks later we examined mitochondrial biogenesis, intramuscular lipids (triacylglycerol, diacylglycerol, ceramide), GLUT4 and FAT levels, insulin-stimulated glucose transport and signalling protein phosphorylation (thymoma viral proto-oncogene 2 [Akt2], Akt substrate of 160 kDa [AS160]), and fatty acid oxidation in subsarcolemmal and intermyofibrillar mitochondria. Electrotransfection yielded physiologically relevant increases in Pgc-1alpha (also known as Ppargc1a) mRNA and protein ( approximately 25%) in lean and obese muscle. This induced mitochondrial biogenesis, and increased FAT and GLUT4 levels, insulin-stimulated glucose transport, and Akt2 and AS160 phosphorylation in lean and obese animals, while bioactive intramuscular lipids were only reduced in obese muscle. Concurrently, PGC-1alpha increased palmitate oxidation in subsarcolemmal, but not in intermyofibrillar mitochondria, in both groups. In obese compared with lean animals, the PGC-1alpha-induced improvement in insulin-stimulated glucose transport was smaller, but intramuscular lipid reduction was greater. Increases in PGC-1alpha levels, similar to those that can be induced by physiological stimuli, altered intramuscular lipids and improved fatty acid oxidation, insulin signalling

  12. A new source of resistance to 2-furaldehyde from Scheffersomyces (Pichia) stipitis for sustainable lignocellulose-to-biofuel conversion.

    Science.gov (United States)

    Wang, Xu; Lewis Liu, Z; Zhang, Xiaoping; Ma, Menggen

    2017-06-01

    Aldehyde inhibitory compounds derived from lignocellulosic biomass pretreatment have been identified as a major class of toxic chemicals that interfere with microbial growth and subsequent fermentation for advanced biofuel production. Development of robust next-generation biocatalyst is a key for a low-cost biofuel production industry. Scheffersomyces (Pichia) stipitis is a naturally occurring C-5 sugar utilization yeast; however, little is known about the genetic background underlying its potential tolerance to biomass conversion inhibitors. We investigated and identified five uncharacterized putative aryl-alcohol dehydrogenase genes (SsAADs) from this yeast as a new source of resistance against biomass fermentation inhibitor 2-furaldehyde (furfural) by gene expression, gene cloning, and direct enzyme assay analysis using partially purified proteins. All five proteins from S. stipitis showed furfural reduction using cofactor NADH. An optimum active temperature was observed at 40 °C for SsAad1p; 30 °C for SsAad3p, SsAad4p, and SsAad5p; and 20 °C for SsAad2p. SsAad2p, SsAad3p, and SsAad4p showed tolerance to a wide range of pH from 4.5 to 8, but SsAad1p and SsAad5p were sensitive to pH changes beyond 7. Genes SsAAD2, SsAAD3, and SsAAD4 displayed significantly enhanced higher levels of expression in response to the challenge of furfural. Their encoding proteins also showed higher levels of specific activity toward furfural and were suggested as core functional enzymes contributing aldehyde resistance in S. stipitis.

  13. Proliferation Vulnerability Red Team report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E. [and others

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  14. Diffusion of global sustainability standards

    OpenAIRE

    Schouten, Greetje; Vellema, Sietze; Wijk, van, C.A.P.

    2016-01-01

    The past two decades saw a rapid proliferation of sustainability standards created by multi-stakeholder partnerships of multinationals and international NGOs. This paper argues that the transformative capacity of these global partnerships to bring about sustainable change largely depends on how well the institutional features of global sustainability standards fit local organizational fields. This paper therefore aims to unravel the dynamics of global-local interactions. To this end, the conc...

  15. Understanding plant defence responses against herbivore attacks: an essential first step towards the development of sustainable resistance against pests.

    Science.gov (United States)

    Santamaria, M Estrella; Martínez, Manuel; Cambra, Inés; Grbic, Vojislava; Diaz, Isabel

    2013-08-01

    Plant-herbivore relationships are complex interactions encompassing elaborate networks of molecules, signals and strategies used to overcome defences developed by each other. Herbivores use multiple feeding strategies to obtain nutrients from host plants. In turn, plants respond by triggering defence mechanisms to inhibit, block or modify the metabolism of the pest. As part of these defences, herbivore-challenged plants emit volatiles to attract natural enemies and warn neighbouring plants of the imminent threat. In response, herbivores develop a variety of strategies to suppress plant-induced protection. Our understanding of the plant-herbivore interphase is limited, although recent molecular approaches have revealed the participation of a battery of genes, proteins and volatile metabolites in attack-defence processes. This review describes the intricate and dynamic defence systems governing plant-herbivore interactions by examining the diverse strategies plants employ to deny phytophagous arthropods the ability to breach newly developed mechanisms of plant resistance. A cornerstone of this understanding is the use of transgenic tools to unravel the complex networks that control these interactions.

  16. Proper Tools Helping Sustainability in Logistics Practice

    NARCIS (Netherlands)

    Alrik Stelling; Erik Koekebakker; Reinder Pieters; Stef Weijers; Nico Lamers; Gerard Vos

    2009-01-01

    Proliferation on sustainability is a must, for quite a lot of companies. Logisticians could use models in attaining sustainability, or at least in understanding its potentials. A sustainable business plan must be based on a clear vision and must be underpinned thoroughly, in order to get the board

  17. SUSTAINABLE CHEMISTRY FOR SUSTAINABLE INDUSTRY

    Directory of Open Access Journals (Sweden)

    G. Rizzuto

    2015-01-01

    Full Text Available Foundry Alfe Chem is an industrial reality working in the field of lubrication and chemical auxiliaries for industrial processes, which falls within the framework of the emerging and increasingly important «green chemistry». The goal of the company is to develop products that are more environmentally friendly by using raw materials from renewable sources; specifically, Foundry Alfe Chem has a program of self-sustainability that contemplates, for the foreseeable future, the direct production of renewable raw materials. The company has developed a new dedicated product line, Olitema, whose purpose is to offer highly technological solutions with complete environmental sustainability. In this context, Foundry Alfe CHEM has created a new product which represents a breakthrough in the class of HFC hydraulic fluids: Ecosafe Plus is a biodegradable fire-resistant hydraulic fluid with high engineering and technological performances, high environmental sustainability and the best security guarantees in workplaces. Its formulation is glycols-free, and it allows for easier disposal of the exhausted fluid, compared to a traditional water/ glycol-based HFC hydraulic fluid. For what concern the technological properties, Ecosafe Plus has been tested by accredited laboratories with tribological trials (4 Ball wear test ASTM D 4172, Ball on disc test ASTM 6425, Brugger test DIN 51347, Vickers test ASTM D 2882, with elastomer compatibility test (ASTM D 471 and biodegradability test (OECD 310 F.

  18. Sustained effect of resistance training on blood pressure and hand grip strength following a detraining period in elderly hypertensive women: a pilot study

    Directory of Open Access Journals (Sweden)

    Nascimento D da C

    2014-01-01

    effects were sustained after 14 weeks of detraining. Conclusion: Resistance training may be a valuable method to improve muscular strength and blood pressure in elderly people with benefits being maintained up to 14 weeks following training cessation. Keywords: aging, resistance training, hypertension, detraining, elderly

  19. miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer.

    Science.gov (United States)

    Baumgartner, Ulrich; Berger, Fabienne; Hashemi Gheinani, Ali; Burgener, Sabrina Sofia; Monastyrskaya, Katia; Vassella, Erik

    2018-02-19

    Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease. A global understanding of underlying molecular mechanisms of EGFR signaling may improve the management of NSCLC patients. microarray analysis was performed to identify PI3K/AKT-regulated miRNAs. Phosphoproteomic analysis and cell based assays were performed using NSCLC cell lines lentivirally transduced with anti-miR or miR overexpressing constructs. Here, we show that 17 miRNAs including members of the miR-17~ 92 cluster are dysregulated following PI3K/AKT inhibition of EGFR mutant NSCLC cells. Bioinformatics analysis revealed that dysregulated miRNAs act in a concerted manner to enhance the activity of the EGFR signaling pathway. These findings were closely mirrored by attenuation of miR-17~ 92 family member miR-19b in NSCLC cell lines which resulted in reduced phosphorylation of ERK, AKT and STAT and effector proteins in EGFR mutant NSCLC cells. Consistent with this finding, cell cycle progression, clonogenic growth and migration were reduced and apoptosis was enhanced. Co-treatment of NSCLC cells with the tyrosine kinase inhibitor (TKI) gefitinib and anti-miR-19b construct reduced migration and clonogenic growth in a synergistic manner suggesting that EGFR and miR-19b act together to control oncogenic processes. Serine/threonine phosphatase PP2A subunit PPP2R5E and BCL2L11 encoding BIM were identified as major targets of miR-19b by target validation assays. Consistent with this finding, PP2A activity was strongly enhanced in NSCLC transduced with anti-miR-19b construct, but not in

  20. Changes in the cellular microRNA profile by the intracellular expression of HIV-1 Tat regulator: A potential mechanism for resistance to apoptosis and impaired proliferation in HIV-1 infected CD4+ T cells.

    Science.gov (United States)

    Sánchez-Del Cojo, María; López-Huertas, María Rosa; Díez-Fuertes, Francisco; Rodríguez-Mora, Sara; Bermejo, Mercedes; López-Campos, Guillermo; Mateos, Elena; Jiménez-Tormo, Laura; Gómez-Esquer, Francisco; Díaz-Gil, Gema; Alcamí, José; Coiras, Mayte

    2017-01-01

    HIV-1 induces changes in the miRNA expression profile of infected CD4+ T cells that could improve viral replication. HIV-1 regulator Tat modifies the cellular gene expression and has been appointed as an RNA silencing suppressor. Tat is a 101-residue protein codified by two exons that regulates the elongation of viral transcripts. The first exon of Tat (amino acids 1-72) forms the transcriptionally active protein Tat72, but the presence of the second exon (amino acids 73-101) results in a more competent regulatory protein (Tat101) with additional functions. Intracellular, full-length Tat101 induces functional and morphological changes in CD4+ T cells that contribute to HIV-1 pathogenesis such as delay in T-cell proliferation and protection against FasL-mediated apoptosis. But the precise mechanism by which Tat produces these changes remains unknown. We analyzed how the stable expression of intracellular Tat101 and Tat72 modified the miRNA expression profile in Jurkat cells and if this correlated with changes in apoptotic pathways and cell cycle observed in Tat-expressing cells. Specifically, the enhanced expression of hsa-miR-21 and hsa-miR-222 in Jurkat-Tat101 cells was associated with the reduced expression of target mRNAs encoding proteins related to apoptosis and cell cycle such as PTEN, PDCD4 and CDKN1B. We developed Jurkat cells with stable expression of hsa-miR-21 or hsa-miR-222 and observed a similar pattern to Jurkat-Tat101 in resistance to FasL-mediated apoptosis, cell cycle arrest in G2/M and altered cell morphology. Consequently, upregulation of hsa-miR-21 and hsa-miR-222 by Tat may contribute to protect against apoptosis and to anergy observed in HIV-infected CD4+ T cells.

  1. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ.

    Science.gov (United States)

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-09-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)‑induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d‑PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP‑1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity.

  2. Proliferation Security Initiative (PSI)

    National Research Council Canada - National Science Library

    Squassoni, Sharon

    2005-01-01

    President Bush announced the Proliferation Security Initiative (PSI) on May 31, 2003. Since then, 16 nations have pledged their cooperation in interdicting shipments of weapons of mass destruction-related...

  3. Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

    Science.gov (United States)

    Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

    2017-01-23

    We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG 1 after two booster vaccinations, while IgG subtypes IgG 2 and IgG 3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27 high CD38 high ) and mature memory (CD21 - IgM - ) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67 + ) follicular T helper cells and regulatory CXCR5 + CD8 + cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67 + ) CD4 + and CD8 + T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG 1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

  4. Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Yang XL

    2014-06-01

    ability of 231/Gem cells. Western blot analysis showed that treatment with a PI3K/AKT inhibitor decreased the expression levels of p-AKT, p-MEK, p-mTOR, and p-P70S6K; however, treatments with either MEK/MAPK or mTOR inhibitor significantly increased p-AKT expression. Thus, our data suggest that gemcitabine resistance in breast cancer cells is mainly mediated by activation of the PI3K/AKT signaling pathway. This occurs through elevated expression of p-AKT protein to promote cell proliferation and is negatively regulated by the MEK/MAPK and mTOR pathways. Keywords: chemoresistance, gemcitabine, breast cancer

  5. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  6. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  7. Leukemia Inhibitory Factor Downregulates Human Papillomavirus-16 Oncogene Expression and Inhibits the Proliferation of Cervical Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Joseph M. Bay

    2011-01-01

    Full Text Available The constitutive proliferation and resistance to differentiation and apoptosis of neoplastic cervical cells depend on sustained expression of human papillomavirus oncogenes. Inhibition of these oncogenes is a goal for the prevention of progression of HPV-induced neoplasias to cervical cancer. SiHa cervical cancer cells were transfected with an HPV-16 promoter reporter construct and treated with leukemia inhibitory factor (LIF, a human cytokine of the interleukin 6 superfamily. SiHa and CaSki cervical cancer cells were also assessed for proliferation by MTT precipitation, programmed cell death by flow cytometry, and HPV E6 and E7 expression by real-time PCR. LIF-treated cervical cancer cells showed significantly reduced HPV LCR activation, reduced levels of E6 and E7 mRNA, and reduced proliferation. We report the novel use of LIF to inhibit viral oncogene expression in cervical cancer cells, with concomitant reduction in proliferation suggesting re-engagement of cell-cycle regulation.

  8. Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high-grade serous ovarian cancer that distinguish malignant, tumour-sustaining and chemo-resistant ovarian tumour cells.

    Science.gov (United States)

    Chapman-Rothe, N; Curry, E; Zeller, C; Liber, D; Stronach, E; Gabra, H; Ghaem-Maghami, S; Brown, R

    2013-09-19

    In embryonic stem (ES) cells, bivalent chromatin domains containing H3K4me3 and H3K27me3 marks silence developmental genes, while keeping them poised for activation following differentiation. We have identified gene sets associated with H3K27me3 and H3K4me3 marks at transcription start sites in a high-grade ovarian serous tumour and examined their association with epigenetic silencing and malignant progression. This revealed novel silenced bivalent marked genes, not described previously for ES cells, which are significantly enriched for the PI3K (P<10(-7)) and TGF-β signalling pathways (P<10(-5)). We matched histone marked gene sets to gene expression sets of eight normal fallopian tubes and 499 high-grade serous malignant ovarian samples. This revealed a significant decrease in gene expression for the H3K27me3 and bivalent gene sets in malignant tissue. We then correlated H3K27me3 and bivalent gene sets to gene expression data of ovarian tumour 'stem cell-like' sustaining cells versus non-sustaining cells. This showed a significantly lower expression for the H3K27me3 and bivalent gene sets in the tumour-sustaining cells. Similarly, comparison of matched chemo-sensitive and chemo-resistant ovarian cell lines showed a significantly lower expression of H3K27me3/bivalent marked genes in the chemo-resistant compared with the chemo-sensitive cell line. Our analysis supports the hypothesis that bivalent marks are associated with epigenetic silencing in ovarian cancer. However it also suggests that additional tumour specific bivalent marks, to those known in ES cells, are present in tumours and may potentially influence the subsequent development of drug resistance and tumour progression.

  9. Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

    NARCIS (Netherlands)

    Korsheninnikova, E.; van der Zon, G. C. M.; Voshol, P. J.; Janssen, G. M.; Havekes, L. M.; Grefhorst, A.; Kuipers, F.; Reijngoud, D. -J.; Romijn, J. A.; Ouwens, D. M.; Maassen, J. A.

    2006-01-01

    Aims/hypothesis Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods Chronic hepatic

  10. Fuel Sustainability And Actinide Production Of Doping Minor Actinide In Water-Cooled Thorium Reactor

    Science.gov (United States)

    Permana, Sidik

    2017-07-01

    Fuel sustainability of nuclear energy is coming from an optimum fuel utilization of the reactor and fuel breeding program. Fuel cycle option becomes more important for fuel cycle utilization as well as fuel sustainability capability of the reactor. One of the important issues for recycle fuel option is nuclear proliferation resistance issue due to production plutonium. To reduce the proliferation resistance level, some barriers were used such as matrial barrier of nuclear fuel based on isotopic composition of even mass number of plutonium isotope. Analysis on nuclear fuel sustainability and actinide production composition based on water-cooled thorium reactor system has been done and all actinide composition are recycled into the reactor as a basic fuel cycle scheme. Some important parameters are evaluated such as doping composition of minor actinide (MA) and volume ratio of moderator to fuel (MFR). Some feasible parameters of breeding gains have been obtained by additional MA doping and some less moderation to fuel ratios (MFR). The system shows that plutonium and MA are obtained low compositions and it obtains some higher productions of even mass plutonium, which is mainly Pu-238 composition, as a control material to protect plutonium to be used as explosive devices.

  11. Sustainable agriculture

    National Research Council Canada - National Science Library

    Lichtfouse, Eric

    2009-01-01

    ... : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 Part I CLIMATE CHANGE Soils and Sustainable Agriculture: A Review : : : : : : : : : : : : : : : : : : : : : : : : : : Rattan Lal 15 Soils and Food Sufficiency...

  12. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  13. Antimicrobial resistance in human and animal pathogens in Zambia, Democratic Republic of Congo, Mozambique and Tanzania: an urgent need of a sustainable surveillance system

    Science.gov (United States)

    2013-01-01

    A review of the published and unpublished literature on bacterial resistance in human and animals was performed. Sixty-eight articles/reports from the Democratic Republic of Congo (DRC), Mozambique, Tanzania and Zambia were reviewed. The majority of these articles were from Tanzania. There is an increasing trend in the incidence of antibiotic resistance; of major concern is the increase in multidrug- resistant Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Vibrio cholera, non-typhoid Salmonella and other pathogens responsible for nosocomial infections. The increase in methicillin- resistant Staphylococcus aureus and extended-spectrum beta-lactamase (ESBL) producers in the countries under review confirms the spread of these clones worldwide. Clinical microbiology services in these countries need to be strengthened in order to allow a coordinated surveillance for antimicrobial resistance and provide data for local treatment guidelines and for national policies to control antimicrobial resistance. While the present study does not provide conclusive evidence to associate the increasing trend in antibiotic resistance in humans with the use of antibiotics in animals, either as feed additives or veterinary prescription, we strongly recommend a one-health approach of systematic surveillance across the public and animal health sectors, as well as the adherence to the FAO (Food and Agriculture Organization)-OIE (World Organization of animal Health) –WHO(World Health Organization) recommendations for non-human antimicrobial usage. PMID:24119299

  14. Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Lieke Thorsten

    2012-10-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. Results By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. Conclusion In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.

  15. The sustained mood-stabilizing effect of memantine in the management of treatment resistant bipolar disorders: findings from a 12-month naturalistic trial

    National Research Council Canada - National Science Library

    Koukopoulos, Athanasios; Serra, Giulia; Koukopoulos, Alexia E; Reginaldi, Daniela; Serra, Gino

    2012-01-01

    We have recently provided preliminary clinical observations indicating that memantine, as augmenting agent, was associated with a meaningful antimanic and mood-stabilizing effect in treatment-resistant bipolar disorders...

  16. The Fiction of Sustainability

    DEFF Research Database (Denmark)

    Mubanda Rasmussen, Louise

    at maintaining and attracting new donor funding? Despite this contradiction, various actors in the HIV/AIDS field continuously invoke the doctrine of sustainability (Swidler & Watkins) as the remedy for problems such as 'donor dependency' and 'high turn-over' among volunteers. Based on five months ethnographic...... research with organisations providing help to "Orphans and Vulnerable Children" in Malawi, this paper discusses how donors, international and local NGOs, and CBOs all participate in keeping alive 'the fiction of sustainability', each for their different reasons. Rather than overt resistance to the power...

  17. JPRS Report, Proliferation Issues

    Science.gov (United States)

    1992-05-27

    JPRS-TND-92-016 27 MAY 1992 JPRS Repor Proliferation Issues ÄBpxovea tcz pursue ieiaaM| Ipfe. fötmbuasa OsüoaÜBd .^L ■ — —— au »** 19980112...6 MOROCCO Berrada on Proposed Nuclear Power Plant [ MAROC SOIR 22 Apr] 6 JPRS-TND-92-016 27 May 1992 2 CENTRAL EURASIA Proposals on...three days of talks here on normalizing relations with Japan, which were largely stalemated over Tokyo’s demand for Pyongyang’s assurance that it did

  18. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  19. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  20. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  1. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance

    Science.gov (United States)

    Thakur, Meghna Das; Salangsang, Fernando; Landman, Allison S.; Sellers, William R.; Pryer, Nancy K.; Levesque, Mitchell P.; Dummer, Reinhard; McMahon, Martin; Stuart, Darrin D.

    2014-01-01

    Mutational activation of BRAF is the most prevalent genetic alteration in human melanoma, with ≥ 50% of tumours expressing the BRAF(V600E) oncoprotein1,2. Moreover, the marked tumour regression and improved survival of late-stage BRAF-mutated melanoma patients in response to treatment with vemurafenib demonstrates the essential role of oncogenic BRAF in melanoma maintenance3,4. However, as most patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance is critical to providing improved therapy5. Here we investigate the cause and consequences of vemurafenib resistance using two independently derived primary human melanoma xeno-graft models in which drugresistanceisselected by continuous vemurafenib administration. In one of these models, resistant tumours show continued dependency on BRAF(V600E) → MEK → ERK signalling owing to elevated BRAF(V600E) expression. Most importantly, we demonstrate that vemurafenib-resistant melanomas become drug dependent for their continued proliferation, such that cessation of drug administration leads to regression of established drug-resistant tumours. We further demonstrate that a discontinuous dosing strategy, which exploits the fitness disadvantage displayed by drug-resistant cells in the absence of the drug, forestalls the onset of lethal drug-resistant disease. These data highlight the concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance. Such observations may contribute to sustaining the durability of the vemurafenib response with the ultimate goal of curative therapy for the subset of melanoma patients with BRAF mutations. PMID:23302800

  2. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus

    NARCIS (Netherlands)

    Asseldonk, van E.J.P.; Poppel, van P.C.M.; Ballak, D.B.; Stienstra, Rinke; Netea, M.G.; Tack, C.J.

    2015-01-01

    Inflammation associated with obesity is involved in the development of insulin resistance. We hypothesized that anti-inflammatory treatment with the Interleukin-1 receptor antagonist anakinra would improve insulin sensitivity.In an open label proof-of-concept study, we included overweight

  3. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  4. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...

  5. Sustaining dairy

    NARCIS (Netherlands)

    Villarreal Herrera, Georgina

    2017-01-01

    Dairy in Europe has undergone many changes in the last few years—the abolition of milk production quotas being a fundamental one. This study explores these changes in relation to the sustained social and environmental viability of the sector and how dairy processors' sustainability

  6. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    . Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...... campus performance....

  7. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  8. Sustainable Learning

    Science.gov (United States)

    Cadwell, Louise; Dillon, Robert

    2011-01-01

    Green schools have moved into a new era that focuses on building a culture of sustainability in every aspect of learning in schools. In the early stages of sustainability education, the focus was on recycling and turning off the lights. Now, students and adults together are moving into the areas of advocacy and action that are based on a deep…

  9. Use of Biomass as a Sustainable and Green Fuel with Alkali-Resistant DeNOx Catalysts based on Sulfated or Tungstated Zirconia

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Fehrmann, Rasmus; Christensen, Claus H.

    poisons is the use of supports with highly acidic properties, which would interact stronger with potassium than the vanadium species. Among those, sulfated and tungstated zirconica appears very attractive, since their surface acidity can be tuned in a wide range by varying the preparation procedure, WOX......, sulfated, and tungstated zirconia were prepared and tested. The influence of potassium additives on the acidity and activity was studied and the results were compared with traditional V2O5-WO3/TiO2 catalyst. Resistance of the catalysts towards poisoning with potassium was found to depend dramatically...... on the crystallinity and surface acidity of the support used. Better resistance of the samples based on sulfated and tungstated zirconia seems to be connected with the fact that a significant part of the potassium on the surface of the catalyst preferentially interact with strong acid sites of the support thus...

  10. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    Science.gov (United States)

    2011-01-01

    Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation. PMID:21745358

  11. Treatment of Triple Negative Breast Cancer With TORC1/2 Inhibitors Sustains a Drug-resistant and Notch-dependent Cancer Stem Cell Population

    Science.gov (United States)

    Bhola, Neil E.; Jansen, Valerie M.; Koch, James P.; Li, Hua; Formisano, Luigi; Williams, Janice A.; Grandis, Jennifer R.; Arteaga, Carlos L.

    2015-01-01

    Approximately 30% of triple negative breast cancers (TNBC) harbor molecular alterations in PI3K/mTOR signaling, but therapeutic inhibition of this pathway has not been effective. We hypothesized that intrinsic resistance to TORC1/2 inhibition is driven by cancer stem cell (CSC)-like populations that could be targeted to enhance the antitumor action of these drugs. Therefore, we investigated the molecular mechanisms by which PI3K/mTOR inhibitors affect the stem-like properties of TNBC cells. Treatment of established TNBC cell lines with a PI3K/mTOR inhibitor or a TORC1/2 inhibitor increased the expression of CSC markers and mammosphere formation. A CSC-specific PCR array revealed that inhibition of TORC1/2 increased FGF1 and Notch1 expression. Notch1 activity was also induced in TNBC cells treated with TORC1/2 inhibitors and associated with increased mitochondrial metabolism and FGFR1 signaling. Notably, genetic and pharmacological blockade of Notch1 abrogated the increase in CSC markers, mammosphere formation, and in vivo tumor-initiating capacity induced by TORC1/2 inhibition. These results suggest that targeting the FGFR-mitochondrial metabolism-Notch1 axis prevents resistance to TORC1/2 inhibitors by eradicating drug-resistant CSCs in TNBC, and may thus represent an attractive therapeutic strategy to improve drug responsiveness and efficacy. PMID:26676751

  12. A Conceptual Study on the Sustainability of Nuclear Power

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kwon, Eun Ha; Choi, Hang Bok; Lim, Chae Young; Yoon, Ji Sup; Park, Seong Won

    2007-06-15

    Due to the current population growth and industrialization, energy consumption is increasing continuously. The world population and energy consumption were 2.5 billion and 1.5 billion tons of equivalent oil in 1950, but they are expected to be 9.2 billion and 60 tons, respectively, in 2100. This amount of energy consumption will result in an exhaustion of fossil resources and cause a serious environmental problem such as global warming. Therefore it is necessary to develop sustainable energy resources that maintain current economic growth and social welfare level without burdening a next generation's life style. Nuclear energy has an excellent competitiveness from the viewpoint of a sustainability. Especially nuclear power can effectively reduce greenhouse gas emissions and can be developed in a complementary way with a new and renewable energy, such as solar and wind power, and hydrogen energy. It is expected that nuclear power will maintain its sustainability in the following directions: Implementation of a fast reactor fuel cycle with a high uranium utilization efficiency, Implementation of a pyro-process with an excellent proliferation-resistance, Activity on the enhancement of a domestic social acceptance for nuclear power, International cooperation and joint research for the enhancement of an international nuclear transparency, Optimization of a nuclear grid structure through an accommodation of new and renewable energy resources, Application to a mass production of hydrogen energy.

  13. Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in Rwanda

    NARCIS (Netherlands)

    Kateera, Fredrick; Nsobya, Sam L.; Tukwasibwe, Steven; Hakizimana, Emmanuel; Mutesa, Leon; Mens, Petra F.; Grobusch, Martin P.; van Vugt, Michèle; Kumar, Nirbhay

    2016-01-01

    Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years

  14. Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.

    Science.gov (United States)

    Zhu, Jiaxue; Gu, Jianhua; Ma, Jie; Xu, Zhixing; Tao, Hairong

    2015-01-01

    Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet. We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model. Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA. HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

  15. Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.; Thompson, Sandra E.

    2009-06-01

    This Preliminary Assessment draft report will present the results of a literature search and preliminary assessment of the body of research, analysis methods, models and data deemed to be relevant to the Utility of Social Modeling for Proliferation Assessment research. This report will provide: 1) a description of the problem space and the kinds of information pertinent to the problem space, 2) a discussion of key relevant or representative literature, 3) a discussion of models and modeling approaches judged to be potentially useful to the research, and 4) the next steps of this research that will be pursued based on this preliminary assessment. This draft report represents a technical deliverable for the NA-22 Simulations, Algorithms, and Modeling (SAM) program. Specifically this draft report is the Task 1 deliverable for project PL09-UtilSocial-PD06, Utility of Social Modeling for Proliferation Assessment. This project investigates non-traditional use of social and cultural information to improve nuclear proliferation assessment, including nonproliferation assessment, proliferation resistance assessments, safeguards assessments and other related studies. These assessments often use and create technical information about the State’s posture towards proliferation, the vulnerability of a nuclear energy system to an undesired event, and the effectiveness of safeguards. This project will find and fuse social and technical information by explicitly considering the role of cultural, social and behavioral factors relevant to proliferation. The aim of this research is to describe and demonstrate if and how social science modeling has utility in proliferation assessment.

  16. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  17. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  18. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  19. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003......), urban design competitions are understudied mechanisms for bringing about field level changes. Drawing on actor network theory, this paper examines how urban design competitions may bring about changes within the professional field through the use of intermediaries such as a sustainable planning....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  20. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  1. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  2. The Boy Who Learned To Read Through Sustained Video Game Play: Considering Systemic Resistance To The Use Of New Texts In The Classroom

    Directory of Open Access Journals (Sweden)

    Rochelle SKOGEN

    2012-12-01

    Full Text Available Various studies have discussed the pedagogical potential of video game play in the classroom but resistance to such texts remains high. The study presented here discusses the case study of one young boy who, having failed to learn to read in the public school system was able to learn in a private Sudbury model school where video games were not only allowed but considered important learning tools. Findings suggest that the incorporation of such new texts in today’s public schools have the potential to motivate and enhance the learning of children.

  3. THE BOY WHO LEARNED TO READ THROUGH SUSTAINED VIDEO GAME PLAY: CONSIDERING SYSTEMIC RESISTANCE TO THE USE OF ‘NEW TEXTS’ IN THE CLASSROOM

    Directory of Open Access Journals (Sweden)

    Rochelle SKOGEN

    2012-05-01

    Full Text Available Various studies have discussed the pedagogical potential of video game play in the classroom but resistance to such texts remains high. The study presented here discusses the case study of one young boy who, having failed to learn to read in the public school system was able to learn in a private Sudbury model school where video games were not only allowed but considered important learning tools. Findings suggest that the incorporation of such new texts in today’s public schools have the potential to motivate and enhance the learning of children.

  4. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-07-10

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  5. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-03-13

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts. news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  6. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-07-16

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  7. JPRS report. Proliferation issues

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-02-21

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons-relevant technologies. Foreign Broadcast Information Service (FBIS) and Joint Publications Research Service (JPRS) publications contain political, military, economic, environmental, and sociological news, commentary, and other information, as well as scientific and technical data and reports. All information has been obtained from foreign radio and television broadcasts, news agency transmissions, newspapers, books, and periodicals. Items generally are processed from the first or best available sources. It should not be inferred that they have been disseminated only in the medium, in the language, or to the area indicated. Items from foreign language sources are translated; those from English-language sources are transcribed. Except for excluding certain diacritics, FBIS renders personal names and place-names in accordance with the romanization systems approved for U.S. Government publications by the U.S. Board of Geographic Names.

  8. Sustainable finance

    OpenAIRE

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence Sustainable Business Administration & Management Accounting, Financial Leadership and what is the importance of CSR in the financial sector

  9. SUSTAINABLE TRANSPORTATION

    Directory of Open Access Journals (Sweden)

    Linda STEG

    2007-01-01

    Full Text Available This paper discusses possible contributions of psychologists to sustainable transportation. It is argued that in order to reach sustainable transportation, among others, behaviour changes of individual car users are needed. As transport policies will be more effective if they target important antecedents of travel behaviour, first, factors influencing such behaviour are discussed. It is argued that car use is very attractive and sometimes even necessary for many different reasons. This implies that a combination of policies is called for, each targeting different factors that support car use and hinder the use of more sustainable modes of transport. Next, the paper elaborates on policy strategies that may be employed to achieve sustainable transportation by changing car use. Increasing the attractiveness of sustainable transport modes by means of pull measures seems not sufficient to reduce the level of car use. Besides, car use should be made less attractive by means of push measures to force drivers to reconsider their travel behaviour. The acceptability of such policies may be increased by clearly communicating the aim of these policies, and the expected positive consequences (e.g., less congestion, improved environmental quality. Moreover, possible negative effects for individual freedom may be compensated by implementing additional policies aimed at facilitating the use of sustainable transport modes.

  10. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  11. Ezrin regulating the cytoskeleton remodelling is required for hypoxia-induced Myofibroblast proliferation and migration

    Directory of Open Access Journals (Sweden)

    Bin eYi

    2015-03-01

    Full Text Available Background: Hypoxia pulmonary arterial hypertension (HPAH is a disease of the small vessels characterized by sustained vasoconstriction, thickening of arterial walls, vascular remodelling, and progressive increase in pulmonary vascular resistance, thus leading to right heart failure and finally death. Recent evidence demonstrated that massive Pulmonary Artery Smooth Muscle-like Cells (PASMLCs accumulating in the intima might also be developed from the differentiation of Pulmonary Myofibroblast (PMF of tunica media. And PMF appeared the phenomenon of the cytoskeleton remodeling. So, it would be important in the clarification of the pivotal factors controlling this cytoskeleton structure change. Methods: PMFs were cultured from the normal rats and then divided into three groups and incubated by nomal or hypoxic conditions respectively. mRNA level was evaluated by real time reverse transcription polymerase chain reaction, and protein expression was detected by western blot. Cell proliferation was determined by the MTT and thymidine incorporation assay. Results: Here, we report that the hypoxia increased the expression levels of Ezrin mRNA and protein in PMFs, which might explain the expression of cytoskeletal proteins (Destrin, a1-actin, and a1-tubulin in PMFs was significantly induced by hypoxia. After inhibiting Ezrin in PMFs by siRNA transfection, we found the over-expression of cytoskeletal proteins induced by hypoixa were significantly suppressed at all time points. Additionally, we found that hypoxia or over-expression of Ezrin through Ad-Ezrin transfection significantly increases the proliferation and migration of PMFs, and which could be inverted by the transfection of siRNA. Conclusion: These findings suggest that Ezrin regulating of aberrant dysregulation of cytoskeletal proteins may be the major cause of PMFs' proliferation and migration under the condition of hypoxia and may, therefore, play a fundamental role in the accumulation of

  12. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Directory of Open Access Journals (Sweden)

    Karolina A. Zielińska

    2017-09-01

    Full Text Available Malaria-associated acute respiratory distress syndrome (MA-ARDS is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ and Plasmodium berghei NK65 (PbNK65. Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES by 90% and both CCL2 (MCP-1 and CXCL10 (IP-10 by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1 unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK, JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs.

  13. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    The willingness of public authority to delegate social and environmental regulation to the private sector has varied from sector to sector, but has often led to the establishment of ‘voluntary’ standards and certifications on sustainability. Many of these have taken the form of ‘stewardship...... councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity......-specific sustainability situations into a form that not only ‘hears more voices’ (as in ‘multi-stakeholder’), but also portrays to give them equal standing at the table of negotiations (roundtable), thus raising higher expectations on accountability, transparency and inclusiveness. In this article, I examine to what...

  14. Sustainability Evaluation.

    Science.gov (United States)

    Stichnothe, Heinz

    2017-03-17

    The long-term substitution of fossil resources can only be achieved through a bio-based economy, with biorefineries and bio-based products playing a major role. However, it is important to assess the implications of the transition to a bio-based economy. Life cycle-based sustainability assessment is probably the most suitable approach to quantify impacts and to identify trade-offs at multiple levels. The extended utilisation of biomass can cause land use change and affect food security of the most vulnerable people throughout the world. Although this is mainly a political issue and governments should be responsible, the responsibility is shifted to companies producing biofuels and other bio-based products. Organic wastes and lignocellulosic biomass are considered to be the preferred feedstock for the production of bio-based products. However, it is unlikely that a bio-based economy can rely only on organic wastes and lignocellulosic biomass.It is crucial to identify potential problems related to socio-economic and environmental issues. Currently there are many approaches to the sustainability of bio-based products, both quantitative and qualitative. However, results of different calculation methods are not necessarily comparable and can cause confusion among decision-makers, stakeholders and the public.Hence, a harmonised, globally agreed approach would be the best solution to secure sustainable biomass/biofuels/bio-based chemicals production and trade, and to avoid indirect effects (e.g. indirect land use change). However, there is still a long way to go.Generally, the selection of suitable indicators that serve the purpose of sustainability assessment is very context-specific. Therefore, it is recommended to use a flexible and modular approach that can be adapted to various purposes. A conceptual model for the selection of sustainability indicators is provided that facilitates identifying suitable sustainability indicators based on relevance and significance in a

  15. A comparison of liver protein changes in mice and hamsters treated with the peroxisome proliferator Wy-14,643.

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C. S.; Tollaksen, S. L.; Cunningham, M. L.; Center for Mechanistic Biology and Biotechnology; National Inst. of Environmental Health Sciences

    1998-01-01

    Interspecies differences in the liver response to Wy-14,643, a potent peroxisome proliferator in rats and mice, have been demonstrated. While both rats and mice show dramatic increases in the number of peroxisomes, the activity of peroxisomal enzymes involved in the {beta}-oxidation of fatty acids, and heptocyte replication, Syrian hamsters have a more moderate peroxisome proliferation response and no sustained increase in cell replication. Rats and mice, but not hamsters, develop hepatocellular carcinoma after prolonged exposure to Wy-14,643. To further characterize this species difference, two-dimensional gel electrophoresis (2-DE) has been used to compare the effect of 14-day exposure to various dietary concentrations of Wy-14,643 on liver protein expression in male mice and hamsters. Digitized images of the 2-DE protein maps were searched for significant changes. The peroxisome bifunctional enzyme (PBE) enoyl CoA hydratase/3-hydroxyacyl dehydrogenase, which migrates to the same position in mouse and hamster liver protein 2-DE patterns, increased in abundance by more than three times the control level in both mice and hamsters. In addition to the quantitative change in PBE, significant quantitative changes (P < 0.001) were found in 49 mouse liver proteins (47 decreasing and 2 increasing) and in 35 hamster liver proteins (27 decreasing and 8 increasing). There was little overlap in the mouse and hamster proteins showing quantitative changes in response to Wy-14,643, with the exception of PBE and one unidentified liver protein with an approximate molecular weight of 50 000. These results show that although peroxisome proliferation occurs in the livers of both mice and hamsters exposed to Wy-14,643, other species-specific changes in proteins occur that are independent of the peroxisome proliferation response and that could be related to species-specific susceptibility or resistance to liver tumor induction.

  16. Managed Sustainable Development Classification Of Resources And Goods amp Services Calculating Sustainable Growth Rate And The Sustainable Development Index

    Directory of Open Access Journals (Sweden)

    Shubham Saxena

    2017-05-01

    Full Text Available Macro-level manmade problems can often be best solved by understanding and manipulating the economics behind it. The world today is facing genuine problems of scarcity of resources and environmental amp ecological issues in view of intergenerational equity. The paper proposes a new approach of identification and classification of i Resources and ii Goods and services in the context of sustainable development. Every economy has ambitious economic growth aspirations which are often found conflicting with the commitments on natural resource conservation and climate change obligations. The proposed methodology is a reconciliation of the aspired economic growth of a region and the conservation of the resources and nature. The paper employs contribution of different types of goods and services in the gross domestic product GDP of a region to analyze sustainability of development. The important parameters that the paper establishes are Sustainability Ratio R Sustainable Growth Rate SG and the Sustainable Development Index SI. These parameters can be used to compare the sustainable development level of different regions. Ensuring natural resource and environmental sustainability will eventually ensure economic sustainability. The paper considers resource depletion concerns as well as the environmental pollutants biological risks carbon footprint warhead proliferation et cetera thereby ensuring all round sustainability from survival to economic end. The sustainability analysis is done for long periods such as 50 years 100 years et cetera. The index shows how sustainable the development of an economy is and how sustainability it is growing. The presently much revered GDP growth numbers are directionless it does not tell the type of growth an economy essentially has. The direction should be sustainability which the paper stresses upon. An illustration of sustainability analysis of India is also done. Such indices can help identifying sustainably developing

  17. PMP27 PROMOTES PEROXISOMAL PROLIFERATION

    NARCIS (Netherlands)

    MARSHALL, PA; KRIMKEVICH, YI; LARK, RH; DYER, JM; VEENHUIS, M; GOODMAN, JM; Krimkevich, Yelena I.; Lark, Richard H.; Dyer, John M.; Goodman, Joel M.

    Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by

  18. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  19. Sustainable agriculture

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

    New farming techniques, better food security. Since 1970, IDRC-supported research has introduced sustainable agricultural practices to farmers and communities across the devel- oping world. The result: higher productivity, less poverty, greater food security, and a healthier environment. Opportunities grow on trees in ...

  20. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Abstract. This article examines the concept of sustainable development after the Post-. 2015 Paris Climate Change Agreement with particular emphasis on Ethiopia. Various African countries are vulnerable to climate change, as is evidenced by recent droughts. Ethiopia is selected as a case study in light of its pace in.

  1. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  2. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  3. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. It The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  4. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  5. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  6. Sustainable finance

    NARCIS (Netherlands)

    dr. Margreet F. Boersma-de Jong

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  7. Cell Proliferation and Cytotoxicity Assays.

    Science.gov (United States)

    Adan, Aysun; Kiraz, Yağmur; Baran, Yusuf

    Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.

  8. Is light water reactor technology sustainable?

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, G. [Stanford Univ., Dept. of Economics, CA (United States); Van der Zwaan, B. [Vrije Univ., Amsterdam, Inst. for Environmental Studies (Netherlands)

    2001-07-01

    This paper proposes criteria for determining ''intermediate sustainability'' over a 500-year horizon. We apply these criteria to Light Water Reactor (LWR) technology and the LWR industry. We conclude that LWR technology does not violate intermediate sustainability criteria for (1) environmental externalities, (2) worker and public health and safety, or (3) accidental radioactive release. However, it does not meet criteria to (1) efficiently use depleted uranium and (2) avoid uranium enrichment technologies that can lead to nuclear weapons proliferation. Finally, current and future global demand for LWR technology might be below the minimum needed to sustain the current global LWR industry. (author)

  9. Soil biodiversity for agricultural sustainability

    NARCIS (Netherlands)

    Brussaard, L.; Ruiter, de P.C.; Brown, G.G.

    2007-01-01

    We critically highlight some evidence for the importance of soil biodiversity to sustaining (agro-)ecosystem functioning and explore directions for future research. We first deal with resistance and resilience against abiotic disturbance and stress. There is evidence that soil biodiversity does

  10. The sustainable nuclear energy technology platform. A vision report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    Nuclear fission energy can deliver safe, sustainable, competitive and practically carbon-free energy to Europe's citizens and industries. Within the framework of the Strategic Energy Technology Plan (SET Plan), the European Commission's stakeholders in this field have formulated a collective vision of the contributions this energy could make towards Europe's transition to a low-carbon energy mix by 2050, with the aim of integrating and expanding R and D capabilities in order to further this objective. The groundwork has been prepared by the stakeholders listed in Annex II, within the framework of two EURATOM FP6 (Sixth Framework Programme) Coordination Actions, namely SNF-TP (Sustainable Nuclear Fission Technology Platform) and PATEROS (Partitioning and Transmutation European Road-map for Sustainable Nuclear Energy), with contributions from Europe's technical safety organisations. This vision report prepares the launch of the European Technology Platform on Sustainable Nuclear Energy (SNE-TP). It proposes a vision for the short-, medium- and long-term development of nuclear fission energy technologies, with the aim of achieving a sustainable production of nuclear energy, a significant progress in economic performance, and a continuous improvement of safety levels as well as resistance to proliferation. In particular, this document proposes road-maps for the development and deployment of potentially sustainable nuclear technologies, as well as actions to harmonize Europe's training and education, whilst renewing its research infrastructures. Public acceptance is also an important issue for the development of nuclear energy. Therefore, research in the fields of nuclear installation safety, protection of workers and populations against radiation, management of all types of waste, and governance methodologies with public participation will be promoted. The proposed road-maps provide the backbone for a strategic research agenda (SRA) to maintain

  11. SUSTAINABLE CORPORATE AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2017-06-01

    Full Text Available In recent decades, the image of the international business environment has changed significantly. Studies conducted by UNCTAD shows that corporate phenomenon developments in the world economy is growing. Without claiming to present an exhaustive topic so vast we tried to capture some "facets" of sustainable development from the perspective of multinational corporations, given the expansion of these economic entities and strengthening their power in the global economy. We present more negative aspects of the actions of multinational corporations in terms of sustainable development, it is very important to know both sides of the coin, which will not only help transnational giants including release. Based on issues such as corporate social responsibility, environmental pollution and workers' rights, we sought to counter official statements. The conclusion is that these economic entities are real forces that can not be ignored in today's world and the obvious problem of sustainable development can not be addressed independently of the phenomenon, context we also identified some possible solutions to conflict of corporations and essence of the concept of sustainable development.

  12. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...... biophysical, distributional and economic conditions for high consumption in rich countries and then zooms in on the coevolution of provision systems and consumption, and how consumption is shaped by practices and projects in everyday life. Furthermore, the paper discusses whether and how transition...

  13. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems that ...... that need urgent action. The built environment is an obvious area to put effort into because of the large and cost-effective energy saving potential and potential for Renewable Energy-based supply systems for buildings.......The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  14. Sustainable and Superior Heat-Resistant Alginate Nonwoven Separator of LiNi0.5Mn1.5O4/Li Batteries Operated at 55 °C.

    Science.gov (United States)

    Wen, Huijie; Zhang, Jianjun; Chai, Jingchao; Ma, Jun; Yue, Liping; Dong, Tiantian; Zang, Xiao; Liu, Zhihong; Zhang, Botao; Cui, Guanglei

    2017-02-01

    High-voltage lithium-ion batteries have become a major research focus. As a major part of lithium batteries, the separator plays a critical role in the development of high-voltage lithium batteries. Herein, we demonstrated a sustainable and superior heat-resistant alginate nonwoven separator for high-voltage (5 V) lithium batteries. It was demonstrated that the resultant alginate nonwoven separator exhibited better mechanical property (37 MPa), superior thermal stability (up to 150 °C), and higher ionic conductivity (1.4 × 10 -3 S/cm) as compared to commercially available polyolefin (PP) separator. More impressively, the 5 V class LiNi 0.5 Mn 1.5 O 4 (LNMO)/Li cell with this alginate nonwoven separator delivered much better cycling stability (maintaining 79.6% of its initial discharge capacity) than that (69.3%) of PP separator after 200 cycles at an elevated temperature of 55 °C. In addition, the LiFePO 4 /Li cell assembled with such alginate nonwoven separator could still charge and discharge normally even at an elevated temperature of 150 °C. The above-mentioned fascinating characteristics of alginate separator provide great probability for its application for high-voltage (5 V) lithium batteries at elevated temperatures.

  15. Domestic Politics and Nuclear Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chul Min; Yim, Man Sung [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables.

  16. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Pentacyclic nitrofurans that rapidly kill nifurtimox-resistant trypanosomes.

    Science.gov (United States)

    Bruhn, David F; Wyllie, Susan; Rodríguez-Cortés, Adaris; Carrillo, Angela K; Rakesh; Guy, R Kiplin; Fairlamb, Alan H; Lee, Richard E

    2016-04-01

    In response to reports of Trypanosoma brucei resistance to the nitroaromatic drug nifurtimox, we evaluated the potential of antituberculosis nitrofuran isoxazolines as inhibitors of trypanosome growth. The susceptibility of T. brucei brucei was assessed in vitro. The lowest effective concentration to inhibit growth (EC90) against drug-susceptible and -resistant parasites, time-kill kinetics, reversibility of inhibition and propensity for P-glycoprotein-mediated exclusion from the blood-brain barrier were determined. Nitrofuran isoxazolines were potent inhibitors of T. brucei brucei proliferation at nanomolar concentrations, with pentacyclic nitrofurans being 100-fold more potent than nifurtimox. Activity was sustained against nifurtimox-resistant parasites, suggesting the possibility of a unique mechanism of activation and potential for use in the treatment of drug-resistant infections. Exposure of parasites to the maximum concentrations of Compound 15 achieved in vivo with oral dosing yielded >2 logs of irreversible killing in nifurtimox-resistant trypanosome infections. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Really sustainable?

    DEFF Research Database (Denmark)

    Hadjimichael, Maria; Hegland, Troels Jacob

    2016-01-01

    In recent years, there has been a proliferation in environmental, market-based product certification schemes. Typically, certifying bodies provide labels that assure that the products have been extracted or produced using environmentally (and sometimes socially) responsible practices. Ideally......, consumers can then make informed choices and select certified products over non-certified. We discuss the advantages as well as the limitations associated with such market-based certification systems drawing on three case studies of Marine Stewardship Council (MSC) certification: the Alaska Pollock Fishery......, the Faroe Islands' Saithe Fishery, and the Australian Northern Prawn Fishery. Based on our cases, a key indication is that incentives generated by market forces create a risk of certification schemes making questionable claims in order to increase and retain market shares. Monopolization of the concept...

  19. GREEN AND SUSTAINABLE REMEDIATION BEST MANAGEMENT PRACTICES

    Science.gov (United States)

    2016-09-07

    resistant vegetation for revegetation of excavated areas, along with removal of invasive species.  Minimize the amount of noise , dust, light...chemical oxidation (ISCO), thermal treatment, groundwater extraction and treatment (GWET), and excavation. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION... resistive heating FY fiscal year GHG greenhouse gas GSR green and sustainable remediation GWET groundwater extraction and treatment ISCO in

  20. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...... as subject to substantial regulatory compliance obligations external to the process of procurement. In short, procurement has been transformed in a way to enforce regulatory obligations that are not intrinsic to the process of buying. This leads to the conclusion that questions such as the cost and trade...

  1. Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal piglets.

    Science.gov (United States)

    Reznikov, Elizabeth A; Comstock, Sarah S; Yi, Cuiyi; Contractor, Nikhat; Donovan, Sharon M

    2014-09-01

    Lactoferrin is a bioactive milk protein that stimulates cell proliferation in vitro; however, limited in vivo evidence exists to allow lactoferrin to be incorporated into infant formula. Herein, the effect of dietary bovine lactoferrin (bLF) on neonatal intestinal growth and maturation was investigated guided by the hypothesis that bLF would increase cellular proliferation leading to functional differences in neonatal piglets. Colostrum-deprived piglets were fed formula containing 0.4 [control (Ctrl)], 1.0 (LF1), or 3.6 (LF3) g bLF/L for the first 7 or 14 d of life. To provide passive immunity, sow serum was provided orally during the first 36 h of life. Intestinal cell proliferation, histomorphology, mucosal DNA concentration, enzyme activity, gene expression, and fecal bLF content were measured. Intestinal enzyme activity, DNA concentration, and villus length were unaffected by bLF. However, crypt proliferation was 60% greater in LF1- and LF3-fed piglets than in Ctrl piglets, and crypt depth and area were 20% greater in LF3-fed piglets than in Ctrl piglets. Crypt cells from LF3-fed piglets had 3-fold higher β-catenin mRNA expression than did crypt cells from Ctrl piglets. Last, feces of piglets fed bLF contained intact bLF, suggesting that some bLF was resistant to digestion and could potentially affect intestinal proliferation through direct interaction with intestinal epithelial cells. This study is the first to our knowledge to show that dietary bLF stimulates crypt cell proliferation in vivo. The increased β-catenin expression indicates that Wnt signaling may in part mediate the stimulatory effect of bLF on intestinal cell proliferation. © 2014 American Society for Nutrition.

  2. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  3. Modeling hormonal control of cambium proliferation.

    Science.gov (United States)

    Oles, Vladyslav; Panchenko, Alexander; Smertenko, Andrei

    2017-01-01

    Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork) for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1) auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2) auxin and cytokinin pathways negatively regulate each other; (3) hormonal pathways act redundantly in sustaining cambium activity; (4) individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

  4. Modeling hormonal control of cambium proliferation.

    Directory of Open Access Journals (Sweden)

    Vladyslav Oles

    Full Text Available Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1 auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2 auxin and cytokinin pathways negatively regulate each other; (3 hormonal pathways act redundantly in sustaining cambium activity; (4 individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

  5. Nuclear Proliferation: A Historical Overview

    Science.gov (United States)

    2008-03-01

    unsuccessful, however, and in 1981 Egypt ratified the Nuclear Non-Proliferation Treaty. In 1982 Egypt’s Hydrometallurgy Pilot Plant for reprocessing...Country Profile: Egypt,” http://www.iaea.org/DataCenter/index.html (accessed ɠ/8/2007>). 1982: Hydrometallurgy Pilot Plant for reprocessing

  6. Nuclear Proliferation Technology Trends Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  7. anterior hyaloidal fibrovascular proliferation (ahfvp)

    African Journals Online (AJOL)

    Okonkwo

    fibrovascular proliferation in ischaemic diabetic eyes is known to occur predominantly in the region posterior to the equator, ie, the pre-equatorial fundus. There is a. 5 preponderance of posterior neovascularization occurring in proliferative diabetic retinopathy. This posterior. 7,8,9 proliferative disease in ischaemic diabetic ...

  8. Development of resistance to photodynamic therapy (PDT) in human breast cancer cells is photosensitizer-dependent: Possible mechanisms and approaches for overcoming PDT-resistance.

    Science.gov (United States)

    Olsen, Cathrine Elisabeth; Weyergang, Anette; Edwards, Victoria Tudor; Berg, Kristian; Brech, Andreas; Weisheit, Sabine; Høgset, Anders; Selbo, Pål Kristian

    2017-11-15

    Here we report on the induction of resistance to photodynamic therapy (PDT) in the ABCG2-high human breast cancer cell line MA11 after repetitive PDT, using either Pheophorbide A (PhA) or di-sulphonated meso-tetraphenylchlorin (TPCS 2a ) as photosensitizer. Resistance to PhA-PDT was associated with enhanced expression of the efflux pump ABCG2. TPCS 2a -PDT-resistance was neither found to correspond with lower TPCS 2a -accumulation nor reduced generation of reactive oxygen species (ROS). Cross-resistance to chemotherapy (doxorubicin) or radiotherapy was not observed. TPCS 2a -PDT-resistant cells acquired a higher proliferation capacity and an enhanced expression of EGFR and ERK1/2. p38 MAPK was found to be a death-signalling pathway in the MA11 cells post TPCS 2a -PDT, contrasting the MA11/TR cells in which PDT generated a sustained phosphorylation of p38 that had lost its death-mediated signalling, and an abrogated activation of its downstream effector MAPKAPK2. No difference in apoptosis, necrosis or autophagy responses was found between the treated cell lines. Development of TPCS 2a -PDT resistance in the MDA-MB-231 cell line was also established, however, p38 MAPK did not play a role in the PDT-resistance. MCF-7 cells did not develop TPCS 2a -PDT-resistance. Photochemical internalisation (PCI) of 1 pM of EGF-saporin induced equal strong cytotoxicity in both MA11 and MA11/TR cells. In conclusion, loss of p38 MAPK-inducing death signalling is the main mechanism of resistance to TPCS 2a -PDT in the MA11/TR cell line. This work provides mechanistic knowledge of intrinsic and acquired PDT-resistance which is dependent on choice of photosensitizer, and suggests PCI as a rational therapeutic intervention for the elimination of PDT-resistant cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  10. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  11. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  12. Sustainable Scientists

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Evan

    2008-12-31

    Scientists are front and center in quantifying and solving environmental problems. Yet, as a spate of recent news articles in scientific journals point out, much can be done to enhance sustainability within the scientific enterprise itself, particularly by trimming the energy use associated with research facilities and the equipment therein (i,ii,iii, iv). Sponsors of research unwittingly spend on the order of $10 billion each year on energy in the U.S. alone, and the underlying inefficiencies drain funds from the research enterprise while causing 80 MT CO2-equivalent greenhouse-gas emissions (see Box). These are significant sums considering the opportunity costs in terms of the amount of additional research that could be funded and emissions that could be reduced if the underlying energy was used more efficiently. By following commercially proven best practices in facility design and operation, scientists--and the sponsors of science--can cost-effectively halve these costs, while doing their part to put society on alow-carbon diet.

  13. Organizational Inertia and Excessive Product Proliferation

    OpenAIRE

    Sakuraki, Rie

    2015-01-01

    This study investigates the internal factors of excessive product proliferation. Since empirical literature on product over-proliferation focused on how to optimize existing product portfolio, the causes of excessive product proliferation have so far attracted little attention. This study employs a case study of Shiseido, a famous Japanese cosmetics company, with particular attention to product proliferation in the Shiseido chain store channel, because external factors are mostly absent from ...

  14. Sustainable agriculture - selected papers

    OpenAIRE

    Krasowicz, Stanisław; Wrzaszcz, Wioletta; Zegar, Jozef St.

    2007-01-01

    The concept of research on socially sustainable agriculture. Features of sustainable agriculture. Sustainability of private farms in the light of selected criteria. Subsistence agricultural holdings and the sustainable development of agriculture. Sustainable farms in the light of the FADN data. Description of organic holdings in Poland.

  15. 15 CFR 12.2 - Undue proliferation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Undue proliferation. 12.2 Section 12.2 Commerce and Foreign Trade Office of the Secretary of Commerce FAIR PACKAGING AND LABELING § 12.2 Undue proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or...

  16. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2010-03-03

    Integrated energy, environment and economics modeling suggests electrical energy use will increase from 2.4 TWe today to 12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources. Thus nuclear power may be needed to provide ~30% by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century proliferation risks are much greater, and more resistant to mitigation. The risks of nuclear power should be compared with the risks of the estimated 0.64oC long-term global surface-average temperature rise predicted if nuclear power were replaced with coal-fired power plants without carbon sequestration. Fusion energy, if developed, would provide a source of nuclear power with much lower proliferation risks than fission.

  17. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2011-04-28

    Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ~12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ~30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

  18. Overview of DOE-NE Proliferation and Terrorism Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sadasivan, Pratap [Los Alamos National Laboratory

    2012-08-24

    Research objectives are: (1) Develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of current reactors; (2) Develop improvements in the affordability of new reactors to enable nuclear energy; (3) Develop Sustainable Nuclear Fuel Cycles; and (4) Understand and minimize the risks of nuclear proliferation and terrorism. The goal is to enable the use of risk information to inform NE R&D program planning. The PTRA program supports DOE-NE's goal of using risk information to inform R&D program planning. The FY12 PTRA program is focused on terrorism risk. The program includes a mix of innovative methods that support the general practice of risk assessments, and selected applications.

  19. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  20. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  1. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  2. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  3. Proliferation of life from Enceladus

    Science.gov (United States)

    Czechowski, L.

    2017-09-01

    Enceladus is a medium-sized icy satellite (MIS) of Saturn. MIS are built of mixtures of rocks and ices. In 2014 [4] indicates that conditions in the core of this satellite allow for the life. In fact for hundreds of Myr the conditions in the interior of Enceladus were more favourable for origin of life than on the Earth [5, 6]. Presently we continue the research on the possible mechanism of life proliferation including additionally gravity assist as mechanism for deceleration of the body.

  4. Signals involved in T cell activation. T cell proliferation induced through the synergistic action of anti-CD28 and anti-CD2 monoclonal antibodies

    NARCIS (Netherlands)

    van Lier, R. A.; Brouwer, M.; Aarden, L. A.

    1988-01-01

    Monoclonal antibodies (mAb) directed against the T cell differentiation antigen CD28 (Tp44) induce proliferation of resting T lymphocytes in the presence of phorbol esters. Moreover, it has been reported that such antibodies augment and sustain T cell proliferation induced by soluble antigens,

  5. Sustaining Shipments

    Energy Technology Data Exchange (ETDEWEB)

    Bonnardel-Azzarelli, Betty [World Nuclear Transport Institute, Remo House, 4th Floor, 310-312 Regent Street, London, London W1B 3AX (United Kingdom)

    2009-06-15

    Transport plays an essential role in bringing the benefits of the atom to people the world over. Each day thousands of shipments of radioactive materials are transported on national and international routes. These consignments are essential to many aspects of modern life, from the generation of electricity, to medicine and health, scientific research and agriculture. Maintaining safe, cost-effective transport is essential to support them. Despite an outstanding safety record spanning over 45 years, the transport of radioactive materials cannot and must not be taken for granted. In an era of nuclear expansion, with increased transports required to more destinations, a worrisome trend for global supply is that some shipping companies, air carriers, ports and terminals, have instituted policies of not accepting radioactive materials. Experience has shown that the reasons for delays and denials of shipments are manifold and often have their origin in mis-perceptions about the nature of the materials and the requirements for their safe handling and carriage. There is growing recognition internationally of the problems created by shipment delays and denials and they now are being addressed in a more proactive way by such organisations as the International Atomic Energy Agency (IAEA). The rapidly changing supply-demand equation for fuel cycle services: substantial new nuclear build planned or underway in several countries, twenty-first century 'gold rush' fever in uranium exploration and mining, proposed new mechanisms to assure fuel supply to more countries while minimising proliferation risks. But, can supply to meet demand be assured, unless and until transport can be assured? And is it reasonable to expect that transport can be assured to meet the emerging demand-side of the fuel cycle equation when industry already is facing increased instances of shipment delays and denials? It is a worrisome trend for global supply of Class 7 radioactive materials that

  6. Chemopreventive effects of metformin on obesity-associated endometrial proliferation.

    Science.gov (United States)

    Zhang, Qian; Celestino, Joseph; Schmandt, Rosemarie; McCampbell, Adrienne S; Urbauer, Diana L; Meyer, Larissa A; Burzawa, Jennifer K; Huang, Marilyn; Yates, Melinda S; Iglesias, David; Broaddus, Russell R; Lu, Karen H

    2013-07-01

    Obesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. Zucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro. Streptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner. These findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women. Copyright © 2013 Mosby, Inc. All rights reserved.

  7. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Organizing for Sustainability

    Science.gov (United States)

    Brown, William M.; Hamburger, Michael W.

    2012-01-01

    A successful campus sustainability effort catalyzes broad engagement of the campus community and integration of sustainability principles into the academic and operational components of campus life. Although many universities have embraced sustainability as a new core value, others have been more sluggish in adopting sustainability principles to…

  9. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  10. Sustainability and the anthropogenic alteration of evolutionary processes

    Directory of Open Access Journals (Sweden)

    John Cairns, Jr.

    2004-08-01

    Full Text Available Persuasive evidence indicates that Earth is now experiencing a major biotic crisis. Even if humankind ceases severe stress on natural systems, the crisis will probably disrupt the basic evolutionary processes that characterized the period preceding the agricultural and industrial revolutions.Proliferation of drug and pesticide resistant species and opportunistic species that thrive in human-dominated ecosystems will become increasingly common. The effect on humankind of altering basic evolutionary processes is uncertain because the understanding of these processes is not robust. The probable result will not be an environment as favorable to humans as the one that has existed for most of human history. Humans probably have altered the environment since Homo sapiens first appeared. However, only in the last two centuries has the degree and rate of change reached levels now considered by many people to be ‘normal’, even though the record shows they are not.Greatly improved technology has facilitated increased exploitation of natural resources to unsustainablelevels. This exploitation, in turn, has led to exponential human population growth, which has depleted natural capital (living systems and the services they provide. Economic globalization has ensured that ecosystems far distant from consumers can be and are profitably exploited. Economicgrowth has become a universal mantra that is coupled with a conviction that such growth can continue indefinitely on a finite planet. A major paradigm shift is essential if sustainable use of the planet is to become a reality.

  11. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  12. Sustainable Investment. Literature Overview

    Energy Technology Data Exchange (ETDEWEB)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-08-15

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns sustainability at the investment, fund or portfolio level and involves screening the sustainability of companies before investing in them. This report highlights leading literature and empirical findings on 'sustainable investment', amongst others addressing the economic rationale for CSR and SRI. This report is part of a set of SEO-reports on finance and sustainability. The other reports deal with: Financing the Transition to Sustainable Energy; Carbon Trading; Innovations in financing environmental and social sustainability.

  13. Induction of apoptosis and inhibition of angiogenesis by PEGylated liposomal quercetin in both cisplatin-sensitive and cisplatin-resistant ovarian cancers.

    Science.gov (United States)

    Long, Qida; Xiel, Yao; Huang, Yanqing; Wu, Qinjie; Zhang, Hecheng; Xiong, Shaoquan; Liu, Yingwei; Chen, Lijuan; Wei, Yuquan; Zhao, Xia; Gong, Changyang

    2013-06-01

    The clinical efficiency of cisplatin against ovarian cancer is often limited by the development of drug resistance. In this work, we investigated PEGylated liposomal quercetin (Lipo-Que) on cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) human ovarian cancer models in vitro and in vivo to reveal whether a cisplatin-resistant ovarian cancer has susceptibility to quercetin (Que) and the mechanism of its antitumor activity. Lipo-Que was prepared using a solid dispersion method, and the obtained Lipo-Que is monodisperse with a mean diameter of 163 +/-10 nm. Besides, in vitro drug release assay showed a sustained release behavior of Lipo-Que. In vitro experiments suggested that Lipo-Que inhibited cell proliferation, induced apoptosis, and induced cell cycle arrest in both A2780s and A2780cp cells. Furthermore, antitumor activity of Lipo-Que was investigated in both cisplatin-sensitive and cisplatin-resistant human ovarian tumor xenograft models in nude mice. Lipo-Que significantly suppressed tumor growth in both models in comparison with free Que, blank liposomes (Lipo), or normal saline (NS). Furthermore, immunohistochemistry and immunofluorescence tests revealed that Lipo-Que induced apoptosis, decreased microvessel density, and inhibited proliferation of tumors in both A2780s and A2780cp tumor models. Therefore, our results suggest that Lipo-Que is an effective agent to inhibit tumor growth in both cisplatin-sensitive and cisplatin-resistant human ovarian cancers.

  14. Strengthening the nuclear-reactor fuel cycle against proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Travelli, A.; Snelgrove, J.; Persiani, P. [Argonne National Lab., IL (United States). Arms Control and Nonproliferation Program

    1992-12-31

    Argonne National Laboratory (ANL) conducts several research programs that serve to reduce the risks of fissile-material diversion from the nuclear-reactor fuel cycle. The objectives are to provide economical and efficient neutron or power generation with the minimum of inherent risks, and to further minimize risks by utilizing sophisticated techniques to detect attempts at material diversion. This paper will discuss the Reduced Enrichment Research and Test Reactor (RERTR) Program, the Isotope Correlation Technique (ICT), and Proliferation-Resistant Closed-Cycle Reactors. The first two are sponsored by the DOE Office of Arms Control and Nonproliferation.

  15. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...... by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  16. Myostatin inhibits proliferation and insulin-stimulated glucose uptake in mouse liver cells.

    Science.gov (United States)

    Watts, Rani; Ghozlan, Mostafa; Hughey, Curtis C; Johnsen, Virginia L; Shearer, Jane; Hittel, Dustin S

    2014-06-01

    Although myostatin functions primarily as a negative regulator of skeletal muscle growth and development, accumulating biological and epidemiological evidence indicates an important contributing role in liver disease. In this study, we demonstrate that myostatin suppresses the proliferation of mouse Hepa-1c1c7 murine-derived liver cells (50%; p myostatin-responsive transcript in skeletal muscle, revealed a significant downregulation (25% and 50%, respectively; p myostatin-treated mice and liver cells. The importance of Malat1 in liver cell proliferation was confirmed via arrested liver cell proliferation (p Myostatin also significantly blunted insulin-stimulated glucose uptake and Akt phosphorylation in liver cells while increasing the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS), a protein that is essential for cancer cell proliferation and insulin-stimulated glucose transport. Together, these findings reveal a plausible mechanism by which circulating myostatin contributes to the diminished regenerative capacity of the liver and diseases characterized by liver insulin resistance.

  17. The perils of proliferation: Organization theory, deterrence theory, and the spread of nuclear weapons

    Energy Technology Data Exchange (ETDEWEB)

    Sagan, S.D. (Stanford Univ., CA (United States))

    What is missing in the literature on nuclear proliferation is an alternative theory of the consequences of nuclear proliferation; the effects of nuclear weapons on the likelihood of war. This article presents such an alternative, rooted in organizational theory, which leads to a more pessimistic assessment of the future prospects for peace. Professional military organizations display strong proclivities toward organizational behaviors that lead to deterrence failures. Such organizational proclivities can be effectively countered only by tight and sustained civilian control of the military. There are strong reasons to believe that future nuclear-armed states will lack such positive mechanisms of civilian control.

  18. Antimicrobial chemotherapy and Sustainable Development: The ...

    African Journals Online (AJOL)

    Antimicrobial chemotherapy and Sustainable Development: The past, The Current Trend, and the futu. ... Antimicrobial chemotherapy is a highly valued medical science which has shaped modern humanity in a phenomenal fashion. Within the past half century, ... Key Words; Antimicrobials, microbial resistance, diseases ...

  19. Identification of transcriptional networks involved in peroxisome proliferator chemical-induced hepatocyte proliferation

    Science.gov (United States)

    Peroxisome proliferator chemical (PPC) exposure leads to increases in rodent liver tumors through a non-genotoxic mode of action (MOA). The PPC MOA includes increased oxidative stress, hepatocyte proliferation and decreased apoptosis. We investigated the putative genetic regulato...

  20. Diffusion of global sustainability standards: The institutional fit of the ASC-shrimp standard in Indonesia

    NARCIS (Netherlands)

    G. Schouten (Greetje); S.R. Vellema (Sietze); J.C.A.C. van Wijk (Jeroen)

    2016-01-01

    markdownabstractThe past two decades saw a rapid proliferation of sustainability standards created by multi-stakeholder partnerships of multinationals and international NGOs. This paper argues that the transformative capacity of these global partnerships to bring about sustainable change largely

  1. Proliferation after the Iraq war; La proliferation apres la guerre d'Irak

    Energy Technology Data Exchange (ETDEWEB)

    Daguzan, J.F

    2004-09-15

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  2. Sustaining Rural Communities through Sustainable Agriculture.

    Science.gov (United States)

    Ikerd, John

    A 5-year collaborative project between Missouri, Michigan State, and Nebraska Universities to provide new opportunities for rural community self-development through sustainable agriculture had mixed results. This happened because community members did not understand the principles of sustainability, and because the extension education system was…

  3. Control of cell proliferation by Myc

    DEFF Research Database (Denmark)

    Bouchard, C; Staller, P; Eilers, M

    1998-01-01

    Myc proteins are key regulators of mammalian cell proliferation. They are transcription factors that activate genes as part of a heterodimeric complex with the protein Max. This review summarizes recent progress in understanding how Myc stimulates cell proliferation and how this might contribute ...

  4. Teaching Activities on Horizontal Nuclear Proliferation.

    Science.gov (United States)

    Zola, John

    1990-01-01

    Provides learning activities concerning the horizontal proliferation of nuclear weapons. Includes step-by-step directions for four activities: (1) the life cycle of nuclear weapons; (2) nuclear nonproliferation: pros and cons; (3) the nuclear power/nuclear weapons connection; and (4) managing nuclear proliferation. (NL)

  5. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1995-11-17

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

  6. Making the Hidden Curriculum Visible: Sustainability Literacy in Higher Education

    Science.gov (United States)

    Winter, Jennie; Cotton, Debby

    2012-01-01

    Despite strong political support for the development of sustainability literacy amongst the UK graduates, embedding sustainability in the higher education curriculum has met with widespread indifference, and in some cases, active resistance. However, opportunities exist beyond the formal curriculum for engaging students in learning about…

  7. Sustainable Marketing : The Importance of Being a Sustainable Business

    OpenAIRE

    Reutlinger, Janina

    2012-01-01

    This thesis deals with sustainable marketing, as well as the necessity for more sustainability. The purpose of this thesis was to determine the importance of sustainable marketing for companies. The theoretical part is divided into sustainability and sustainable marketing. Sustainability covers current issues and sustainable development, which form a background for a better understanding of sustainable marketing. Sustainable marketing includes a definition of the concept, as well as susta...

  8. Identificatio of banana varieties with resistance to nematodes in ...

    African Journals Online (AJOL)

    Musa spp.) production worldwide. Identification of banana varieties with resistance to nematodes may be the best option for sustainable nematode management. The objective of the experiment was to evaluate banana varieties with resistance ...

  9. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  10. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    Analysing processes of social learning this work addresses how action research can further new research orientations towards sustainability. Empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating...... on urban sustainability the need to move towards sustainability at societal level is conceptualised as a democratic challenge questioning the way we live on planet earth. By understanding sustainability as an immanent and emergent ability of ecological and social life, continuously to renew itself without...... eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming to provide local citizens...

  12. Handbook of sustainable engineering

    CERN Document Server

    Lee, Kun-Mo

    2013-01-01

    "The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

  13. FORUM: Is Ecotourism Sustainable?

    Science.gov (United States)

    Wall

    1997-07-01

    / It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

  14. Livestock biodiversity and sustainability

    NARCIS (Netherlands)

    Hoffmann, I.

    2011-01-01

    Sustainable development equally includes environmental protection including biodiversity, economic growth and social equity, both within and between generations. The paper first reviews different aspects related to the sustainable use of livestock biodiversity and property regimes that influence

  15. Sustainable Public Bids

    Directory of Open Access Journals (Sweden)

    Gil César Costa de Paula

    2016-06-01

    Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

  16. Indicators for environmental sustainability

    DEFF Research Database (Denmark)

    Dong, Yan; Hauschild, Michael Zwicky

    2017-01-01

    . In this study, we reviewed indicators applied in life cycle assessment (LCA), planetary boundary framework (PB), and Sustainable Development Goals (SDGs) developed under United Nation. The aim is to 1) identify their applications and relevant decision context; 2) Review their indicators and categorize them......Decision making on sustainable consumption and production requires scientifically based information on sustainability. Different environmental sustainability targets exist for specific decision problems. To observe how well these targets are met, relevant environmental indicators are needed...

  17. Sustainable Learning Organizations

    Science.gov (United States)

    Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

    2011-01-01

    Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

  18. Measuring Educational Sustainability

    Science.gov (United States)

    Selvanathan, Rani G.

    2013-01-01

    There are many definitions that are attributable to the meaning of sustainability. Sustainability can be viewed as long-lasting, effective result of a project, venture, action, or investment without consuming additional future resources. Because of the wide nature of its applicability, a universal measure of sustainability is hard to come by. This…

  19. ORNL Annual Sustainability Report

    Energy Technology Data Exchange (ETDEWEB)

    Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-02-01

    As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

  20. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2017-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  1. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2017-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report ’ i...

  2. Lean maturity, lean sustainability

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke; Nielsen, Jacob

    2007-01-01

    Although lean is rapidly growing in popularity, its implementation is far from problem free and companies may experience difficulties sustaining long term success. In this paper, it is suggested that sustainable lean requires attention to both performance improvement and capability development...... that support lean capability development and consequently, lean sustainability....

  3. Food sustainability: diverging interpretations

    NARCIS (Netherlands)

    Aiking, H.; de Boer, J.

    2004-01-01

    The concept of sustainability in general and food sustainability, in particular, entails many aspects and many interpretations. During a conference on food sustainability a broad, multidisciplinary picture was painted and many key issues were dealt with, from ecology, economy and society. In

  4. Transferring Education for Sustainability

    Science.gov (United States)

    Gafoor, Kunnathodi Abdul; Umer Farooque, T. K.

    2013-01-01

    Sustainability stands for sustaining the past, meeting needs of the present without compromising the ability to meet future needs. It should meet the individual and social needs, present and future needs local and global needs. A sustainable education that meets this requirements surely be a transferable education; an education that transfers from…

  5. Sustainability: An Overview.

    Science.gov (United States)

    Wormsley, W. E.

    1990-01-01

    This article introduces a group of six papers on sustainability of programs for visually handicapped persons in developing countries. Sustainability is discussed from an anthropological perspective, noting the importance of a social soundness analysis and a social impact assessment, enemies of sustainability, and the need for broad local input in…

  6. Sustainability in logistics practice

    NARCIS (Netherlands)

    Hans-Heinrich Glöckner; Reinder Pieters; Stef Weijers

    2009-01-01

    This conceptual paper wants to emphasis the use of the concept of sustainability within logistics and especially transportation. While working on a new tool to help companies develop sustainable European networks, we discovered that we want to use a specific concept of sustainability: People, planet

  7. Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM and 18F-FLT) in a Dog with Fibrosarcoma

    DEFF Research Database (Denmark)

    Zornhagen, Kamilla; Clausen, Malene; Hansen, Anders Elias

    2015-01-01

    Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management...

  8. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  9. The Microbiome and Sustainable Healthcare

    Science.gov (United States)

    Dietert, Rodney R.; Dietert, Janice M.

    2015-01-01

    Increasing prevalences, morbidity, premature mortality and medical needs associated with non-communicable diseases and conditions (NCDs) have reached epidemic proportions and placed a major drain on healthcare systems and global economies. Added to this are the challenges presented by overuse of antibiotics and increased antibiotic resistance. Solutions are needed that can address the challenges of NCDs and increasing antibiotic resistance, maximize preventative measures, and balance healthcare needs with available services and economic realities. Microbiome management including microbiota seeding, feeding, and rebiosis appears likely to be a core component of a path toward sustainable healthcare. Recent findings indicate that: (1) humans are mostly microbial (in terms of numbers of cells and genes); (2) immune dysfunction and misregulated inflammation are pivotal in the majority of NCDs; (3) microbiome status affects early immune education and risk of NCDs, and (4) microbiome status affects the risk of certain infections. Management of the microbiome to reduce later-life health risk and/or to treat emerging NCDs, to spare antibiotic use and to reduce the risk of recurrent infections may provide a more effective healthcare strategy across the life course particularly when a personalized medicine approach is considered. This review will examine the potential for microbiome management to contribute to sustainable healthcare. PMID:27417751

  10. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2017-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report...... is then demonstrated, and the strategy of LCA to achieving environmental protection, namely to guide the reduction of environmental impacts per delivery of a function, is explained. The attempt to broaden the scope of LCA, beyond environmental protection, by so-called life cycle sustainability assessment (LCSA......) is outlined. Finally, the limitations of LCA in guiding a sustainable development are discussed....

  11. From sustainable buildings to sustainable business

    OpenAIRE

    Mia Andelin

    2012-01-01

    The United Nations Environment Program (UNEP) Sustainable Buildings & Climate Initiative reports that buildings are responsible for more than 40 percent of global energy use and over one third of global greenhouse gas (GHG) emissions. The construction and real estate sector has the potential to play a significant role in the response to climate change. During the latest years the increase in attention to sustainability and green building by planners, developers, and investors has been remarka...

  12. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...... to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  13. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  14. Sustainability in Business

    DEFF Research Database (Denmark)

    Tollin, Karin; Vej, Jesper

    2012-01-01

    How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level...... of marketing. The central contribution of the typology is a strategic and managerial view on sustainability. Furthermore, the typology shows that sustainability in business is enacted from different areas of competences and fields in the literature (e.g. supply chain management, corporate branding, value...... creation, product innovation and business model innovation). The empirical basis for the typology is an exploratory study of managers' mindsets about sustainability as strategy. Ten top managers involved with integrating sustainability within their companies have been interviewed. In order to reveal...

  15. Fur and Sustainability

    DEFF Research Database (Denmark)

    Skjold, Else; Csaba, Fabian

    2016-01-01

    This paper explores the notion of deeper luxury, which insists that 'real' luxury should involve sustainable practices in the production and consumption of luxury goods. It traces historical and recent developments in the field of fur, to understand the implications, uncertainties and ambiguities...... of luxury’s confrontation with sustainability. Considering fur in relation to future standards for luxury products, we raise questions about moral problematisation and justification of luxury in terms of sustainability. We first examine the encounter of luxury with sustainability and explain...... the significance of the notion of ‘deeper luxury’. After taking stock of the impact of sustainability on luxury and various directions in which sustainable luxury is evolving, we discuss concepts of sustainable development in relation to the history of moral problematisation of luxury. This leads to the case...

  16. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through

  17. Health and sustainability.

    Science.gov (United States)

    Kjӕrgård, Bente; Land, Birgit; Bransholm Pedersen, Kirsten

    2014-09-01

    In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the 'duality of structure' is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion and sustainability. Third, we use examples from agriculture and food production to illustrate that health and sustainability are mutually enabling and constraining. We conclude that while the renewed focus on food security and food inequalities has brought the health and sustainability dimensions of the food system onto the political agenda, the conceptualization of duality between health and sustainability could be a new platform for a critical and theoretical stance towards the market-oriented food system strategy. Thinking along the lines of duality means that the integration of health promotion strategies and sustainable development strategies cannot be based on an approach to integration in which either health or sustainability is given precedence over the other. From a duality perspective, integration means conceiving sustainability from a health perspective and health from a sustainability perspective. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Gomez, Luis [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Alvarez-Lorenzo, Carmen, E-mail: carmen.alvarez.lorenzo@usc.es [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Concheiro, Angel [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Silva, Maite [Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Dominguez, Fernando [Fundación Publica Galega de Medicina Xenómica, Santiago de Compostela (Spain); Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L. [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States); Macossay, Javier, E-mail: jmacossay@utpa.edu [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States)

    2014-07-01

    Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSCs) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young's modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP–PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP–PCL scaffolds hold promise for tissue regeneration applications. - Highlights: • Platelet-rich plasma (PRP) can be adsorbed on electrospun fibers via lyophilization. • PRP coating enhanced mesenchymal stem cell adhesion and proliferation on scaffolds. • PRP-coated scaffolds showed sustained release of growth factors. • Adsorbed PRP provided angiogenic features. • PRP-poly(ε-caprolactone) scaffolds hold promise for tissue regeneration applications.

  19. NATO's Response to the Proliferation Challenge

    National Research Council Canada - National Science Library

    Joseph, Robert

    1996-01-01

    ... operations in an NBC environment. The success of the NATO initiative to counter the proliferation threat, however, will only be assured when allies make national and collective commitments to field the necessary military capabilities...

  20. Handbook for nuclear non-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok

    1997-05-01

    This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs.

  1. Suburbanization and sustainability in metropolitan Moscow.

    Science.gov (United States)

    Mason, Robert J; Nigmatullina, Liliya

    2011-01-01

    Although Soviet-era urban-growth controls produced relatively sustainable metropolitan development patterns, low-density suburban sprawl has accelerated markedly in modern Russia. Distinctive features of Moscow's development history are its greenbelt, which dates from 1935 and is becoming increasingly fragmented, proliferation of satellite cities at the urban fringe, conversion of seasonal dachas into full-time residences, the very exclusive Rublevo Uspenskoe Highway development, and today's crippling traffic congestion. The recent economic crisis has slowed development and actually increased the supply of “economy-class” single-family homes, for which there is much pent-up desire but insufficient credit availability to meet the demand. A renewed commitment to sustainability's triple bottom line—environmental quality, equity, and economic prosperity—will require greater government transparency and fairness, stronger planning controls, and an expanded public transportation system.

  2. Sustaining Collective Action in Urbanizing China

    DEFF Research Database (Denmark)

    Kuang, Xianwen; Goebel, Christian

    2013-01-01

    The recent years have seen a proliferation of scholarship on protests and other forms of collective action in China. Important insights have been gained into how conflicts between social groups and local governments begin, which strategies and instruments protesters apply, and under which...... challenges of sustaining collective action in China: the continuing existence of substantial grievances, the re-activation of strong social ties, the presence of unifying frames and an adaptive protest leadership. The comparison shows that especially the last factor is crucial: while the two villages were...... similar in all other respects, leadership in Village B was far more adaptive in Village A, which goes a long way towards explaining why collective action could be sustained twice as long in Village B....

  3. Institutional arrangements for the reduction of proliferation risks formulation, evaluation, and implementation of institutional concepts

    Energy Technology Data Exchange (ETDEWEB)

    Kratzer, M.B.; Wonder, E.F.; Gray, J.E.; Shantzis, S.B.; Sievering, N.F.; Paige, H.W.; Jones, B.M.

    1979-12-01

    The purpose of this study was to: (1) identify alternative institutional arrangements applicable to the sensitive steps in the back-end of the fuel cycle that might reduce their associated proliferation risks; and (2) assess their advantages and disadvantages from the standpoint of nonproliferation effectiveness and political, economic, and operational acceptability. The concept of international or multinational custody of sensitive materials and facilities was found to offer a high degree of proliferation resistance and to likely be more acceptable to prospective participants than other institutional arrangements that intrude upon proprietary areas, such as facility ownership and management.

  4. [What is sustainability science?].

    Science.gov (United States)

    Wu, Jian-Guo; Guo, Xiao-Chuan; Yang, Jie; Qian, Gui-Xia; Niu, Jian-Ming; Liang, Cun-Zhu; Zhang, Qing; Li, Ang

    2014-01-01

    Sustainability is the theme of our time and also the grandest challenge to humanity. Since the 1970s, the term, sustainable development, has frequently appeared in the scientific literature, governmental documents, media promotions for public goods, and commercial advertisements. However, the science that provides the theoretical foundation and practical guidance for sustainable development--sustainability science--only began to emerge in the beginning of the 21st century. Nevertheless, the field has rapidly developed in depth and expanded in scope during the past decade, with its core concepts and research methods coalescing. China, as the most populous country in the world and home to the philosophical root of sustainability science-the unity of man and nature, is obligated to take upon the challenge of our time, to facilitate global sustainability while pursuing the Chinese Dream, and to play a leading role in the development of sustainability science. Toward this grandiose goal, this paper presents the first Chinese introduction to sustainability science, which discusses its basic concepts, research questions, and future directions. Sustainability science is the study of the dynamic relationship between humans and the environment, particularly focusing on the vulnerability, robustness, resilience, and stability of the coupled human-environment system. It is a transdisciplinary science that integrates natural sciences with humanities and social sciences. It hinges on the environment-economy-society nexus, and merges basic and applied research. The key components of sustainability often change with time, place, and culture, and thus sustainability science needs to emphasize multi-scale studies in space and time, with emphasis on landscapes and regions over a horizon of 50 to 100 years. It needs to focus on the relationship between ecosystem services and human well-being, as influenced by biodiversity and ecosystem processes as well as climate change, land use

  5. decolonising sustainability: subverting and appropriating

    African Journals Online (AJOL)

    magnitude for environmental education. We can speak of sustainable development, sustainable economies, sustainable democracy, a sustainable world order, and sustainable modes of health maintenance, but when we turn to spiritual matters we are faced with the black hole of green· politics: what constitutes sustainable.

  6. Sustainability: Why the Language and Ethics of Sustainability Matter in the Geoscience Classroom

    Science.gov (United States)

    Metzger, Ellen P.; Curren, Randall R.

    2017-01-01

    Because challenges to sustainability arise at the intersection of human and biophysical systems they are inescapably embedded in social contexts and involve multiple stakeholders with diverse and often conflicting needs and value systems. Addressing complex and solution-resistant problems such as climate change, biodiversity loss, and…

  7. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.

    Science.gov (United States)

    Frigault, Matthew J; Lee, Jihyun; Basil, Maria Ciocca; Carpenito, Carmine; Motohashi, Shinichiro; Scholler, John; Kawalekar, Omkar U; Guedan, Sonia; McGettigan, Shannon E; Posey, Avery D; Ang, Sonny; Cooper, Laurence J N; Platt, Jesse M; Johnson, F Brad; Paulos, Chrystal M; Zhao, Yangbing; Kalos, Michael; Milone, Michael C; June, Carl H

    2015-04-01

    This study compared second-generation chimeric antigen receptors (CAR) encoding signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T cells with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to 3 months following a single stimulation through the T-cell receptor (TCR). Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28. Results from gene array and functional assays linked sustained cytokine secretion and expression of T-bet (TBX21), EOMES, and GATA-3 to the effect. Sustained expression of the endogenous IL2 locus has not been reported in primary T cells. Sustained proliferation was dependent on CAR structure and high expression, the latter of which was necessary but not sufficient. The mechanism involves constitutive signaling through NF-κB, AKT, ERK, and NFAT. The propagated CAR T cells retained a diverse TCR repertoire, and cellular transformation was not observed. The CARs with a constitutive growth phenotype displayed inferior antitumor effects and engraftment in vivo. Therefore, the design of CARs that have a nonconstitutive growth phenotype may be a strategy to improve efficacy and engraftment of CAR T cells. The identification of CARs that confer constitutive or nonconstitutive growth patterns may explain observations that CAR T cells have differential survival patterns in clinical trials. ©2015 American Association for Cancer Research.

  8. SMART SUSTAINABLE ISLANDS VS SMART SUSTAINABLE CITIES

    Directory of Open Access Journals (Sweden)

    D. N. Pantazis

    2017-09-01

    Full Text Available This paper has several aims: a the presentation of a critical analysis of the terms “smart sustainable cities” and “smart sustainable islands” b the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors which concern the insular municipalities c the creation of an island’s smartification and sustainability index d the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

  9. Sustainable Building Operation

    DEFF Research Database (Denmark)

    Jensen, Jesper Ole

    2009-01-01

    Energy-savings in the existing building stock have becomes a main goal in national and international policies. Often focus is on building-renovations, whereas the potential of sustainable building operation to a large extent has been neglected. Nevertheless, international research as well...... as practical experiences from Danish housing estates indicates that there are large potentials for energy savings by focusing on the operation of the buildings. We suggest that in order to achieve sustainability in the existing housing, renovation and operations should be seen as integrated parts...... and that sustainable building operation can pave the way for sustainable building renovation. This paper discusses the use of sustainability building operation in Danish housing estates: Which tools, methods and technologies is being used, where are the barriers and where are the potentials? We define sustainable...

  10. Health and Sustainability

    DEFF Research Database (Denmark)

    Land, Birgit; Pedersen, Kirsten Bransholm; Kjærgård, Bente

    2014-01-01

    In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the ‘duality of structure’ is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering...... the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems...... or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion...

  11. Sustainability and Entrepreneurial Action

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.; Anderson, Alistair

    Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital...... instrument in the pursuit of sustainability.  Prior Work - Extant literature identifies two main approaches to sustainable entrepreneurship. (i) traditional exploitation of environmentally relevant opportunities and (ii) institutional entrepreneurship creating opportunities. We identify a novel form......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...

  12. At Home with Sustainability

    DEFF Research Database (Denmark)

    Hale, Lara

    2018-01-01

    of default rules in subconscious decision-making, this research finds that, ultimately, awareness drives the demand necessary for the creation of sustainable consumption. Whereas direct appeal to individuals has a disappointing level of influence on sustainability choices, it is understood that green......-fuel-based energy. To act otherwise requires additional effort and is less likely. Motivated by a need to understand how defaults might bridge standards and sustainable consumption, I investigate how organizational processes potentially lead from standardized green default rules to individual awareness that can...... spread and facilitate sustainable consumption. This paper examines the Active House sustainable building demonstrations in Europe in order to understand how (1) communications and market creation and (2) responsible, user-centered experimentation are organized to move from defaults to sustainable...

  13. ICT innovations for sustainability

    CERN Document Server

    Aebischer, Bernard

    2015-01-01

    ICT Innovations for Sustainability is an investigation of how information and communication technology can contribute to sustainable development. It presents clear definitions of sustainability, suggesting conceptual frameworks for the positive and negative effects of ICT on sustainable development. It reviews methods of assessing the direct and indirect impact of ICT systems on energy and materials demand, and examines the results of such assessments. In addition, it investigates ICT-based approaches to supporting sustainable patterns of production and consumption, analyzing them at various levels of abstraction – from end-user devices, Internet infrastructure, user behavior, and social practices to macro-economic indicators.   Combining approaches from Computer Science, Information Systems, Human-Computer Interaction, Economics, and Environmental Sciences, the book presents a new, holistic perspective on ICT for Sustainability (ICT4S). It is an indispensable resource for anyone working in the area of ICT...

  14. Sustainability and substitutability.

    Science.gov (United States)

    Fenichel, Eli P; Zhao, Jinhua

    2015-02-01

    Developing a quantitative science of sustainability requires bridging mathematical concepts from fields contributing to sustainability science. The concept of substitutability is central to sustainability but is defined differently by different fields. Specifically, economics tends to define substitutability as a marginal concept while fields such as ecology tend to focus on limiting behaviors. We explain how to reconcile these different views. We develop a model where investments can be made in knowledge to increase the elasticity of substitution. We explore the set of sustainable and optimal trajectories for natural capital extraction and built and knowledge capital accumulation. Investments in substitutability through knowledge stock accumulation affect the value of natural capital. Results suggest that investing in the knowledge stock, which can enhance substitutability, is critical to desirable sustainable outcomes. This result is robust even when natural capital is not managed optimally. This leads us to conclude that investments in the knowledge stock are of first order importance for sustainability.

  15. Sustainable Concrete Technology

    Directory of Open Access Journals (Sweden)

    Sim J.

    2015-12-01

    Full Text Available The growing concern over global warming and significant ecological changes requires sustainable development in all fields of science and technology. Concrete not only consumes huge amount of energy and natural sources, but also emits large amount of CO2, mainly due to the production of cement. It is evident that such large amount of concrete production has put significant impact on the energy, resource, environment, and ecology of the society. Hence, how to develop the concrete technology in a sustainable way has become a significant issue. In this paper, some of Korean researches for sustainable development of concrete are presented. These are sustainable strengthening for deteriorated concrete structure, sustainable reinforcement of new concrete structure, sustainable concrete using recycled aggregate and supplementary cementing materials and finally application of each technique to precast concrete.

  16. Sustainable fashion: New approaches

    OpenAIRE

    Niinimäki, Kirsi

    2013-01-01

    This publication is intended to be used as a source of inspiration for designers and companies, and all stakeholders whose interest lies in the area of sustainable fashion. While the strategies for sustainability are complex and approaches are many, this publication presents only a few ways to approach sustainable fashion. I hope the publication offers inspiration on how to make positive change in current practices and how to effect new mindsets, creating transformative fashion. Theoretica...

  17. Education for sustainable development

    DEFF Research Database (Denmark)

    Breiting, Søren

    2009-01-01

     An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....

  18. A highly sustainable house

    OpenAIRE

    Cordero, Raúl; Mercader-Moyano, Pilar (Coordinador)

    2017-01-01

    A sustainable house is capable of generating and self-sustaining energy by itself to function autonomously, that is to say, without depending on external supply networks. That is possible by supplying the internal energy consumption through renewable energy. This work describes and analyzes the construction of a sustainable house in Paute, Ecuador. The goal of this house was to achieve selfsustainability in several aspects such as construction techniques, creative and functi...

  19. Sustainability Assessment Circle

    OpenAIRE

    Schlör, H.; Hake, J.-Fr.

    2015-01-01

    Since the nineteen seventies, science and society have been discussing the worldwide ecological, economic, and social problems caused by industrialization and globalization. Sustainable development is perceived as a strategy for coping with these problems. The Rio +20 conference in 2012 confirmed the sustainability concept and introduced the green economy and the life cycle sustainable assessment as its implementation and operationalization strategy and tool.In the following, we will demonstr...

  20. Sustainability assessment and complementarity

    Directory of Open Access Journals (Sweden)

    Hugo F. Alrøe

    2016-03-01

    Full Text Available Sustainability assessments bring together different perspectives that pertain to sustainability to produce overall assessments, and a wealth of approaches and tools have been developed in the past decades. However, two major problems remain. The problem of integration concerns the surplus of possibilities for integration; different tools produce different assessments. The problem of implementation concerns the barrier between assessment and transformation; assessments do not lead to the expected changes in practice. We aim to analyze issues of complementarity in sustainability assessment and transformation as a key to better handling the problems of integration and implementation. Based on a generalization of Niels Bohr's complementarity from quantum mechanics, we have identified two forms of complementarity in sustainability assessment, observer stance complementarity and value complementarity. Unlike many other problems of sustainability assessment, complementarity is of a fundamental character connected to the very conditions for observation. Therefore, complementarity cannot be overcome methodologically, only handled better or worse. Science is essential to the societal goal of sustainability, but these issues of complementarity impede the constructive role of science in the transition to more sustainable structures and practices in food systems. The agencies of sustainability assessment and transformation need to be acutely aware of the importance of different perspectives and values and the complementarities that may be connected to these differences. An improved understanding of complementarity can help to better recognize and handle issues of complementarity. These deliberations have relevance not only for sustainability assessment, but more generally for transdisciplinary research on wicked problems.

  1. Predicting Sustainable Work Behavior

    DEFF Research Database (Denmark)

    Hald, Kim Sundtoft

    2013-01-01

    . Employee characteristics and general attitudes towards safety and work condition are included in the extended model. A survey was handed out to 654 employees in Chinese factories. This research contributes by demonstrating how employee- characteristics and general attitudes towards safety and work...... condition influence their sustainable work behavior. A new definition of sustainable work behavior is proposed.......Sustainable work behavior is an important issue for operations managers – it has implications for most outcomes of OM. This research explores the antecedents of sustainable work behavior. It revisits and extends the sociotechnical model developed by Brown et al. (2000) on predicting safe behavior...

  2. Sustainability needs the geosciences

    Science.gov (United States)

    Grimm, Nancy; van der Pluijm, Ben

    2012-10-01

    Science, Innovation, and Partnerships for Sustainable Solutions: A National Academies Symposium; Washington, D. C., 16-18 May 2012 It is no longer disputed that humanity has drastically changed the face of the planet and its life-support systems. The sustainability challenge is to meet people's needs today and in the future while sustaining life-support systems. This grand challenge demands a new scientific approach: use-inspired, solution-driven research that consciously links scientific research to societal decision-making and action. Sustainability science may help fulfill that need if it can engage communities of expertise across a wide range of disciplines and sectors, including the geosciences.

  3. Sustainable wireless networks

    CERN Document Server

    Zheng, Zhongming; Xuemin

    2013-01-01

    This brief focuses on network planning and resource allocation by jointly considering cost and energy sustainability in wireless networks with sustainable energy. The characteristics of green energy and investigating existing energy-efficient green approaches for wireless networks with sustainable energy is covered in the first part of this brief. The book then addresses the random availability and capacity of the energy supply. The authors explore how to maximize the energy sustainability of the network and minimize the failure probability that the mesh access points (APs) could deplete their

  4. Sustainable Management of Food

    Science.gov (United States)

    To provide information to organizations to help them implement sustainable food management, including joining the Food Recovery Challenge. To provide education and information to communities and concerned citizens.

  5. Peroxisome Proliferator-Activated Receptors in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Shinji Kume

    2008-01-01

    Full Text Available Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of the renin-angiotensin system. This review summarizes data from clinical and experimental studies regarding the relationship between PPARs and diabetic nephropathy. The therapeutic potential of PPAR agonists in the treatment of diabetic nephropathy is also discussed.

  6. Sustaining Education for Sustainability in Turbulent Times

    Science.gov (United States)

    Smith, Gregory A.; Stevenson, Robert B.

    2017-01-01

    A study of two schools in northern Australia demonstrated the impact on Education for Sustainability (EfS) initiatives of a disruptive policy environment set in motion by neoliberal reforms focused on standards, accountability, and international competitiveness. In one of the schools, a culture characterized by trust and an emphasis on cultivating…

  7. The possibility of life proliferation from Enceladus

    Science.gov (United States)

    Czechowski, Leszek

    2016-04-01

    Introduction: Enceladus is a medium-sized icy satellite (MIS) of Saturn. MIS are built of mixtures of rocks and ices. Enceladus with its radius of 250 km is one of the smallest of MIS, however, it is geologically active. According to [1]: "For life to have emerged […] on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, […] to off-ridge alkaline hydrothermal springs that interfaced with the metal-rich carbonic Hadean Ocean" (see also [2]). We consider here conditions for origin of life in early Enceladus and possible proliferation of the life from this satellite to the rest of Solar System. Mass of serpentinite: The serpentinization on the Earth is found in neovolcanic zones along mid-oceanic spreading centers. However, only in small part of them the hydrothermal activity really occurs. After [3] we consider the following reaction: Mg2SiO4 + MgSiO3 + 2H2O -> Mg3Si2O5(OH)4 . This reaction releases 241 000 J per kg of serpentine produced. Simple calculations (e.g. [4]) indicate that mass fraction of silicatesfmas in Enceladus is ˜0.646, hence the total mass of its silicate is ˜6.97 1019 kg. [4] found that the early core in Enceladus was a relatively cold structure built from loosely packed grains with water between them. At that time, there was not mechanism of removing the water. Since rocks are permeable up to the pressure of ˜300 MPa then the entire core of Enceladus was probably permeable for liquids. This could lead to formation of extensive hydrothermal convective systems. T-p conditions in Enceladus: The pressure in the center of Enceladus is ˜2.3 107 Pa that corresponds to pressure on the depth 2300 m in a terrestrial ocean. The evolution of temperature in the Enceladus interior for the first a few hundreds Myr is considered by [4]. If

  8. Sustainability in Software Engineering

    NARCIS (Netherlands)

    Wolfram, N.J.E.; Lago, P.; Osborne, Francesco

    2017-01-01

    The intersection between software engineering research and issues related to sustainability and green IT has been the subject of increasing attention. In spite of that, we observe that sustainability is still not clearly defined, or understood, in the field of software engineering. This lack of

  9. Engineering Students' Sustainability Approaches

    Science.gov (United States)

    Haase, S.

    2014-01-01

    Sustainability issues are increasingly important in engineering work all over the world. This article explores systematic differences in self-assessed competencies, interests, importance, engagement and practices of newly enrolled engineering students in Denmark in relation to environmental and non-environmental sustainability issues. The…

  10. Education for Sustainable development

    African Journals Online (AJOL)

    The unit-based sustainability assessment tool (USAT) was administered at Masinde Muliro University of. Science and Technology (MMUST), Kenya, between January and March 2012. The assessment focused on establishing to what extent the University integrated sustainability concerns into its core functions of teaching ...

  11. Sustainable consumption and happiness

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2009-01-01

    textabstractOne of the reasons for promoting sustainable consumption is that it may give rise to greater happiness for a greater number, at least in the long run. In this paper I explore the strength of that moral account. I take stock of the assumed effects of sustainable consumption on happiness

  12. Thermodynamics and sustainable development

    NARCIS (Netherlands)

    Cornelissen, Rene

    1997-01-01

    It is the objective of this thesis to demonstrate exergy analysis as a powerful instrument to obtain sustainable development. An important aspect of sustainable development is the minimisation of irreversibilities caused by the use of non-renewables. In order to limit the scope of this thesis

  13. Implementing Sustainable Institutional Practices

    Science.gov (United States)

    Shepard, Joseph; Johnson, Lewis

    2009-01-01

    Recent research has found that few institutions of higher education implemented the necessary strategies to make their campuses sustainable (Thompson and Green 2005). Ironically, universities are the segment of society with the most access to the intellectual capital needed to provide sound sustainable practices and measurements. Having top…

  14. Sustainable Consumption and Happiness

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2004-01-01

    textabstractOne of the reasons for promoting sustainable consumption is that it may give rise to greater happiness for a greater number, at least in the long run. In this paper I explore the strength of that moral account. I take stock of the assumed effects of sustainable consumption on happiness

  15. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.; Hill, G.; Sauerbruch, M.; Hutton, L.; Knowles, R.; Bothwell, K.; Brennan, J.; Jauslin, D.; Holzheu, H.; AlSayyad, N.; Arboleda, G.; Bharne, V.; Røstvik, H.; Kuma, K.; Sunikka-Blank, M.; Glaser, M.; Pero, E.; Sjkonsberg, M.; Teuffel, P.; Mangone, G.; Finocchiaro, L.; Hestnes, A.; Briggs, D.; Frampton, K.; Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The

  16. Sustainability: Cultural Considerations

    Science.gov (United States)

    2006-04-10

    Action for Sustainable Change. New York: American Management Association, 1999. Fullan , Michael . Leadership & Sustainability: System Thinkers...institutional Army. iii ACKNOWLEGMENTS I thank my project advisors, Mr. Michael Cain, Director, US Army Environmental Policy Institute and Mr...U.S. Army Environmental Policy Institute. Interview by author, date, Arlington, VA. 30 Michaels , Ed. “The War for Talent.” Interview by

  17. Leading Sustainability in Schools

    Science.gov (United States)

    Carr, Katie

    2016-01-01

    What is the role of schools, and more specifically school leadership, in the transition to a sustainable future for humankind? What different forms of leadership are needed to enable this role? The challenges are huge and complex and for those of us engaged in promoting sustainability learning, it is clear that the issue has never been more…

  18. Sustainability at BPA 2012

    Energy Technology Data Exchange (ETDEWEB)

    None

    2012-12-01

    BPA’s Sustainability Action Plan is grounded in our commitment to environmental stewardship and Executive Order 13514 that calls on the federal agencies to “lead by example” by setting a 2020 greenhouse gas emissions target, increasing energy efficiency; reducing fleet petroleum consumption; conserving water; reducing waste; supporting sustainable communities; and leveraging federal purchasing power to promoting environmentally responsible products and technologies.

  19. Entrepreneurship, Innovation and Sustainability

    OpenAIRE

    Keijzers, G.; Wempe, J.F.D.B. (Johan)

    2008-01-01

    Today, only a limited number of entrepreneurs and managers are facing up to the relevance of sustainability issues and the ways in which these may affect their own businesses. Even fewer entrepreneurs and managers see sustainability as a potential source of profit. These are the findings resulting from research carried out by Nyenrode Business Universiteit among well over 500 entrepreneurs and managers.

  20. Entrepreneurship, Innovation and Sustainability

    NARCIS (Netherlands)

    Keijzers, G. (Gerard); Wempe, J.F.D.B. (Johan)

    2008-01-01

    Today, only a limited number of entrepreneurs and managers are facing up to the relevance of sustainability issues and the ways in which these may affect their own businesses. Even fewer entrepreneurs and managers see sustainability as a potential source of profit. These are the findings resulting

  1. Sustaining Urban Forests

    Science.gov (United States)

    John F. Dwyer; David J. Nowak; Mary Heather Noble

    2003-01-01

    The significance of the urban forest resource and the powerful forces for change in the urban environment make sustainability a critical issue in urban forest management. The diversity, connectedness, and dynamics of the urban forest establish the context for management that will determine the sustainability of forest structure, health, functions, and benefits. A...

  2. Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Pogribny, Igor P.; Tryndyak, Volodymyr P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Woods, Courtney G. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Witt, Sarah E. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)], E-mail: iir@unc.edu

    2007-12-01

    Peroxisome proliferators are potent rodent liver carcinogens that act via a non-genotoxic mechanism. The mode of action of these agents in rodent liver includes increased cell proliferation, decreased apoptosis, secondary oxidative stress and other events; however, it is not well understood how peroxisome proliferators are triggering the plethora of the molecular signals leading to cancer. Epigenetic changes have been implicated in the mechanism of liver carcinogenesis by a number of environmental agents. Short-term treatment with peroxisome proliferators and other non-genotoxic carcinogens leads to global and locus-specific DNA hypomethylation in mouse liver, events that were suggested to correlate with a burst of cell proliferation. In the current study, we investigated the effects of long-term exposure to a model peroxisome proliferator WY-14,643 on DNA and histone methylation. Male SV129 mice were fed a control or WY-14,643-containing (1000 ppm) diet for one week, five weeks or five months. Treatment with WY-14,643 led to progressive global hypomethylation of liver DNA as determined by an HpaII-based cytosine extension assay with the maximum effect reaching over 200% at five months. Likewise, trimethylation of histone H4 lysine 20 and H3 lysine 9 was significantly decreased at all time points. The majority of cytosine methylation in mammals resides in repetitive DNA sequences. In view of this, we measured the effect of WY-14,643 on the methylation status of major and minor satellites, as well as in IAP, LINE1 and LINE2 elements in liver DNA. Exposure to WY-14,643 resulted in a gradual loss of cytosine methylation in major and minor satellites, IAP, LINE1 and LINE2 elements. The epigenetic changes correlated with the temporal effects of WY-14,643 on cell proliferation rates in liver, but no sustained effect on (c-Myc) promoter methylation was observed. Finally, WY-14,643 had no effect on DNA and histone methylation status in Ppar{alpha}-null mice at any of the

  3. Sustainability and uncertainty

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint

    2007-01-01

    The widely used concept of sustainability is seldom precisely defined, and its clarification involves making up one's mind about a range of difficult questions. One line of research (bottom-up) takes sustaining a system over time as its starting point and then infers prescriptions from...... this requirement. Another line (top-down) takes an economical interpretation of the Brundtland Commission's suggestion that the present generation's needsatisfaction should not compromise the need-satisfaction of future generations as its starting point. It then measures sustainability at the level of society...... a clarified ethical goal, disagreements can arise. At present we do not know what substitutions will be possible in the future. This uncertainty clearly affects the prescriptions that follow from the measure of sustainability. Consequently, decisions about how to make future agriculture sustainable...

  4. Sustainable nuclear energy dilemma

    Directory of Open Access Journals (Sweden)

    Afgan Naim H.

    2013-01-01

    Full Text Available Sustainable energy development implies the need for the emerging potential energy sources which are not producing adverse effect to the environment. In this respect nuclear energy has gained the complimentary favor to be considered as the potential energy source without degradation of the environment. The sustainability evaluation of the nuclear energy systems has required the special attention to the criteria for the assessment of nuclear energy system before we can make firm justification of the sustainability of nuclear energy systems. In order to demonstrate the sustainability assessment of nuclear energy system this exercise has been devoted to the potential options of nuclear energy development, namely: short term option, medium term option, long term option and classical thermal system option. Criteria with following indicators are introduced in this analysis: nuclear indicator, economic indicator, environment indicator, social indicator... The Sustainability Index is used as the merit for the priority assessment among options under consideration.

  5. System Innovation for Sustainability

    DEFF Research Database (Denmark)

    System Innovation for Sustainability 2 focuses on change towards sustainable personal mobility based on implemented cases analysed from a system perspective. It examines what changes can be made to help us reduce our need for mobility, or start to make use of more sustainable mobility systems...... in order to provide sustainable solutions to our current ‘lock-in’ problems. Three major problem areas are considered (the ‘three Cs’): carbon emissions (and the growing contribution of mobility to the climate change crisis), congestion, and casualties. And each strategy proposed addresses one or more...... such as governments, manufacturers and consumers to intervene in the complex system to promote sustainable mobility. It concludes with a reflection on problems, trends and action needed. The ‘System Innovation for Sustainability’ series is the fruit of the first major international research network on SCP...

  6. Sustainability Marketing Commitment

    DEFF Research Database (Denmark)

    Tollin, Karin; Bech Christensen, Lars

    2017-01-01

    Corporate sustainability is an important strategy and value orientation for marketing, but scarce research addresses the organizational drivers and barriers to including it in companies’ marketing strategies and processes. The purpose of this study is to determine levels of commitment to corporate...... sustainability in marketing, processes associated with sustainability marketing commitment, drivers of sustainability marketing at the functional level of marketing, and its organizational context. Using survey data from 269 managers in marketing, covering a broad range of industries in Sweden and Denmark, we...... took a structural modelling approach to examine construct relationships, mediation, and moderation effects. Overall, the findings show that marketing capabilities associated with the innovation of new products, services, and business models constitute a strong driver to leverage sustainability...

  7. Sustainable Housing Design

    DEFF Research Database (Denmark)

    Lauring, Gert Michael

    2016-01-01

    Sustainable Housing Design. Integrating technical and housing quality aspects of sustainable architecture in civil engineering education. Summary An integrated design approach to sustainable architecture is outlined that combines concerns for zero energy building, good indoor climate and adequate...... constructions, private and public outdoor space, housing, urban and architectural quality. The educational framework, curriculum and inte-grated design methods are preconditions for optimizing a design process where technical criteria, functional concerns and housing quality are addressed from the initial...... phases. The outcome shows that integrated design further solutions where sustainable urban forms of settlement can be highly energy efficient while also attractive from a user perspective. Key words: Sustainable architecture, integrated design, zero-energy-housing, dense urban living. 1. Introduction...

  8. Sustainable built environments

    CERN Document Server

    Haase, Dagmar

    2013-01-01

    Sustainable design is a collective process whereby the built environment achieves unprecedented levels of ecological balance through new and retrofit construction, with the goal of long-term viability and humanization of architecture. Focusing on the environmental context, sustainable design merges the natural, minimum resource conditioning solutions of the past (daylight, solar heat, and natural ventilation) with the innovative technologies of the present.  The desired result is an integrated “intelligent” system that supports individual control with expert negotiation for resource consciousness. International experts in the field address the fundamental questions of sustainable design and landscape management: How should the sustainability of landscapes and buildings be evaluated? Which targets have to be set and which thresholds should not be exceeded? What forms of planning and governance structures exist and to what extent do they further the goals of sustainability?  Gathering 30 peer-reviewed ent...

  9. Agroecology and Sustainable Agriculture

    Directory of Open Access Journals (Sweden)

    Fabio Caporali

    Full Text Available In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006, a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. Universities and society as a whole have a responsibility in re-examining current perception of nature, of the world and of human society in the light of natural resources depletion, increasing pollution and social inequalities. The urgency to address sustainability issues is increasingly being reflected in the manner in which institutions of higher education around the world are giving priority to the teaching, research and practice of sustainability. The University of Tuscia is involved in international initiatives concerning teaching and research in Agroecology and Sustainable Agriculture.

  10. Agroecology and Sustainable Agriculture

    Directory of Open Access Journals (Sweden)

    Fabio Caporali

    2011-02-01

    Full Text Available In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006, a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. Universities and society as a whole have a responsibility in re-examining current perception of nature, of the world and of human society in the light of natural resources depletion, increasing pollution and social inequalities. The urgency to address sustainability issues is increasingly being reflected in the manner in which institutions of higher education around the world are giving priority to the teaching, research and practice of sustainability. The University of Tuscia is involved in international initiatives concerning teaching and research in Agroecology and Sustainable Agriculture.

  11. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C. [ed.

    1993-09-07

    Two essays are included in this booklet. Their titles are ``The Dynamics of the NPT Extension Decision`` and ``North Korea`s Nuclear Gambit.`` The first paper discusses the conference to be held in 1995 to review the Nuclear Non-Proliferation Treaty (NPT) which will decide whether the treaty shall continue in force indefinitely, or shall be extended for an additional fixed period or periods. Topics relevant to this discussion are: Arms control issues, the nuclear test ban, the limited test ban treaty, the French nuclear testing moratorium, former Soviet nuclear weapons, Iraq, North Korea, nuclear-weapon-free zones, security, controls on nuclear weapon materials, peaceful uses of nuclear energy, safeguards, politics, and organizational and procedural issues. The second paper examines short, medium, and long term issues entailed in Korea`s nuclear proliferation. Topics considered include: Korean unification, North Korean politics, the nuclear issue as leverage, and the Nuclear Non- Proliferation Treaty.

  12. Sustainable Resilient, Robust & Resplendent Enterprises

    DEFF Research Database (Denmark)

    Edgeman, Rick

    Although organizational resilience and robustness may be cast in many lights, their core constructs are simply represented. Resplendence is, however, a less well-defined and perhaps more transient enterprise condition that is complementary to, but relatively distinct from resilience and robustness....... Resilience may be regarded as enterprise ability to recover or rebound from negative shocks or extreme challenges to its ecosystem (Contu, 2002). Robustness, in contrast to resilience, is not so much enterprise ability to recover from shocks or challenges to its ecosystem, but rather resistance or immunity...... to their impact. Resplendent enterprises are introduced with resplendence referring not to some sort of public or private façade, but instead refers to organizations marked by dual brilliance and nobility of strategy, governance and comportment that yields superior and sustainable triple bottom line performance...

  13. Leukocytic promotion of prostate cellular proliferation.

    Science.gov (United States)

    McDowell, Kristy L; Begley, Lesa A; Mor-Vaknin, Nirit; Markovitz, David M; Macoska, Jill A

    2010-03-01

    Histological evidence of pervasive inflammatory infiltrate has been noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer (PCa). Cytokines known to attract particular leukocyte subsets are secreted from prostatic stroma consequent to aging and also from malignant prostate epithelium. Therefore, we hypothesized that leukocytes associated with either acute or chronic inflammation attracted to the prostate consequent to aging or tumorigenesis may promote the abnormal cellular proliferation associated with BPH and PCa. An in vitro system designed to mimic the human prostatic microenvironment incorporating prostatic stroma (primary and immortalized prostate stromal fibroblasts), epithelium (N15C6, BPH-1, LNCaP, and PC3 cells), and inflammatory infiltrate (HL-60 cells, HH, and Molt-3 T-lymphocytes) was developed. Modified Boyden chamber assays were used to test the ability of prostate stromal and epithelial cells to attract leukocytes and to test the effect of leukocytes on prostate cellular proliferation. Antibody arrays were used to identify leukocyte-secreted cytokines mediating prostate cellular proliferation. Leukocytic cells migrated towards both prostate stromal and epithelial cells. CD4+ T-lymphocytes promoted the proliferation of both transformed and non-transformed prostate epithelial cell lines tested, whereas CD8+ T-lymphocytes as well as dHL-60M macrophagic and dHL-60N neutrophilic cells selectively promoted the proliferation of PCa cells. The results of these studies show that inflammatory cells can be attracted to the prostate tissue microenvironment and can selectively promote the proliferation of non-transformed or transformed prostate epithelial cells, and are consistent with differential role(s) for inflammatory infiltrate in the etiologies of benign and malignant proliferative disease in the prostate. Prostate 70: 377-389, 2010. (c) 2009 Wiley-Liss, Inc.

  14. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  15. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-12-27

    The Director`s Series on Proliferation is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The seven papers presented in this issue cover the following topics: Should the Treaty on the Nonproliferation of Nuclear Weapons (NPT) be amended?; NPT extension - Legal and procedural issues; An Indonesian view of NPT review conference issues; The treaty of Tlatelolco and the NPT - Tools for peace and development; Perspectives on cut-off, weapons dismantlement, and security assurances; Belarus and NPT challenges; A perspective on the chemical weapons convention - Lessons learned from the preparatory commission.

  16. Fatty acids and breast cancer cell proliferation.

    Science.gov (United States)

    Hardy, R W; Wickramasinghe, N S; Ke, S C; Wells, A

    1997-01-01

    We and others have shown that fatty acids are important regulators of breast cancer cell proliferation. In particular individual fatty acids specifically alter EGF-induced cell proliferation in very different ways. This regulation is mediated by an EGFR/G-protein signaling pathway. Understanding the molecular mechanisms of how this signaling pathway functions and how fatty acids regulate it will provide important information on the cellular and molecular basis for the association of dietary fat and cancer. Furthermore these in vitro studies may explain data previously obtained from in vivo animal studies and identify "good" as well as "bad" fatty acids with respect to the development of cancer.

  17. Proliferation risks; Proliferatierisico's

    Energy Technology Data Exchange (ETDEWEB)

    Carchon, R

    1998-09-01

    The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed.

  18. Supervised Semantic Classification for Nuclear Proliferation Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Vatsavai, Raju [ORNL; Cheriyadat, Anil M [ORNL; Gleason, Shaun Scott [ORNL

    2010-01-01

    Existing feature extraction and classification approaches are not suitable for monitoring proliferation activity using high-resolution multi-temporal remote sensing imagery. In this paper we present a supervised semantic labeling framework based on the Latent Dirichlet Allocation method. This framework is used to analyze over 120 images collected under different spatial and temporal settings over the globe representing three major semantic categories: airports, nuclear, and coal power plants. Initial experimental results show a reasonable discrimination of these three categories even though coal and nuclear images share highly common and overlapping objects. This research also identified several research challenges associated with nuclear proliferation monitoring using high resolution remote sensing images.

  19. Making Sustainability: How Fab Labs Address Environmental Issues

    OpenAIRE

    Cindy Kohtala

    2016-01-01

    Digital manufacturing technologies are proliferating and can enable socially significant, innovative new forms of production and consumption. This thesis examines the environmental sustainability issues in peer production and how they are addressed in Fab Labs (fabrication laboratories): shared spaces where users can design and make their own artefacts outside of conventional mass production channels, using, for example, laser cutters, 3D printers and electronics stations. Fab Labs are open t...

  20. Making sustainability : how Fab Labs address environmental issues

    OpenAIRE

    Kohtala, Cindy

    2016-01-01

    Digital manufacturing technologies are proliferating and can enable socially significant, innovative new forms of production and consumption. This thesis examines the environmental sustainability issues in peer production and how they are addressed in Fab Labs (fabrication laboratories): shared spaces where users can design and make their own artefacts outside of conventional mass production channels, using, for example, laser cutters, 3D printers and electronics stations. Fab Labs are open t...

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

    Energy Technology Data Exchange (ETDEWEB)

    Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  2. Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

    Science.gov (United States)

    Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

    2016-07-01

    Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

  3. Sustainable winegrowing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mariani A

    2015-05-01

    Full Text Available Angela Mariani,1 Antonella Vastola2 1Department of Economic and Legal Studies, University Parthenope, Naples, 2School of Agricultural, Forestry, Food and Environmental Sciences, University of Basilicata, Potenza, Italy Abstract: The winegrowing sector worldwide is strongly committed to improving environmental and social sustainability. The aim of this work, based on a literature review, is to highlight current sustainability perspectives and the related main issues. There is a broad consensus that the challenge to achieve a greater spread of sustainable practices is to enhance environmental and social sustainability while maintaining economic viability. From the producers' point of view, the priority is to bridge the still substantial knowledge gaps in terms of perceived environmental benefits, economic benefits, and costs. Thus, an increased research effort focusing on the costs and benefits of different winegrowing practices and technical assistance with implementation might support their diffusion. Moreover, targeted marketing strategies are needed to: enhance consumers' involvement and their attitude toward sustainable wine; improve understanding and use of sustainable labels and claims; and raise awareness of some environmental credentials of wine packaging, mainly with reference to lightweight glass bottles. Keywords: winegrower, sustainability, wine, consumer, marketing strategies

  4. Antibiotic Resistance

    Science.gov (United States)

    ... But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... of an antibiotic. Using antibiotics can lead to resistance. Each time you take antibiotics, sensitive bacteria are ...

  5. Microbial-based evaluation of anaerobic membrane bioreactors (AnMBRs) for the sustainable and efficient treatment of municipal wastewater

    KAUST Repository

    Harb, Moustapha

    2017-03-01

    Conventional activated sludge-based wastewater treatment is an energy and resource-intensive process. Historically it has been successful at producing safely treated wastewater effluents in the developed world, specifically in places that have the infrastructure and space to support its operation. However, with a growing need for safe and efficient wastewater treatment across the world in both urban and rural settings, a paradigm shift in waste treatment is proving to be necessary. The sustainability of the future of wastewater treatment, in a significant way, hinges on moving towards energy neutrality and wastewater effluent reuse. This potential for reuse is threatened by the recent emergence and study of contaminants that have not been previously taken into consideration, such as antibiotics and other organic micropollutants (OMPs), antibiotic resistance genes, and persistent pathogenic bacteria. This dissertation focuses on investigating the use of anaerobic membrane bioreactor (AnMBR) technology for the sustainable treatment of municipal-type wastewaters. Specifically, a microbial approach to understanding biofouling and methane recovery potential in anaerobic MBR systems has been employed to assess different reactor systems’ efficiency. This dissertation further compares AnMBRs to their more widely used aerobic counterparts. This comparison specifically focuses on the removal and biodegradation of OMPs and antibiotics in both anaerobic and aerobic MBRs, while also investigating their effect on the proliferation of antibiotic resistance genes. Due to rising interest in wastewater effluent reuse and the lack of a comprehensive understanding of MBR systems’ effects on pathogen proliferation, this dissertation also investigates the presence of pathogens in both aerobic and anaerobic MBR effluents by using molecularbased detection methods. The findings of this dissertation demonstrate that membrane-associated anaerobic digestion processes have significant

  6. Sustainability Infused Curriculum

    Science.gov (United States)

    Ibarra, D. L.

    2015-12-01

    The Independent Schools Foundation Academy (ISF) in Hong Kong established a sustainability policy in 2015, which explicitly states, "an experimentally integrated, environmentally and ethically sustainable system of science education and conservation practices based on the 2012 Jeju Declaration of the World Conservation Congress will be implemented through the school". ISF Academy is a private Chinese bilingual school in Hong Kong serving over 1500 students K-12, following the framework and curriculum of the International Baccalaureate Organization (IBO). The strategy behind the implementation of this policy includes: development of a scientific sustainable curriculum that is age appropriate; establish a culture of sustainability within the ISF community and beyond to the wider HK community; install sustainable infrastructure that allows students to learn; and learn first hand sustainable living practices. It is well understood that solutions to the environmental challenges facing Hong Kong and our planet will require multiple disciplines. The current sustainability programs at ISF include: a) a whole school aerobic food waste composting system and organic farming, b) energy consumption monitoring of existing buildings, c) upcoming installation of an air pollution monitoring equipment that will correlate with the AQHI data collected by the Hong Kong government, d) a Renewable Energy Education Center (REEC) that will teach students about RE and also produce solar energy for classroom consumption, and e) student lead environmental group that manages the paper and used cooking oil recycling on campus. The Shuyuan Science and Sustainability faculty work closely with classroom teachers to ensure that the above mentioned projects are incorporated into the curriculum throughout the school. Interdisciplinary units (IDU) of study are being developed that encourage faculty and students to work across subject areas. Projects include Personal Projects, Extended Essays

  7. Effects of high glucose on mesenchymal stem cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Li, Yu-Ming; Schilling, Tatjana; Benisch, Peggy

    2007-01-01

    High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase...... was not influenced by HG in both cell types. MSC treatment with HG favored osteogenic differentiation. MSC are resistant to HG toxicity, depending on the stemness of MSC. Proliferation and osteogenic differentiation are stimulated by HG. Effects of HG on the transient amplifying compartment of MSC may differ from...... those in mature cells. Further research is needed to unravel the molecular mechanisms of HG resistance of MSC...

  8. Textiles and clothing sustainability nanotextiles and sustainability

    CERN Document Server

    2017-01-01

    This book highlights the sustainability aspects of textiles and clothing sector in light of nanomaterials and technologies. The invasion of nano in every industrial sector has been important and has made remarkable changes as well as posed new challenges, including the textiles and clothing sector. There is quite a great deal of research happening in terms of nano materials for textiles across the globe, some of which are covered in this book. .

  9. Integrating Sustainability in Organisations: An Activity-Based Sustainability Model

    National Research Council Canada - National Science Library

    Ana Rodríguez-Olalla; Carmen Aviles-Palacios

    2017-01-01

    .... Although global integration models address sustainability in organisations, these models present shortcomings and limitations and do not describe how to achieve the integration of sustainability...

  10. Sustainable Entrepreneurial Orientation: A Business Strategic Approach for Sustainable Development

    National Research Council Canada - National Science Library

    Ana Criado-Gomis; Amparo Cervera-Taulet; Maria-Angeles Iniesta-Bonillo

    2017-01-01

    This paper proposes sustainable entrepreneurial orientation (SEO) as a multidimensional construct that offers researchers the possibility of empirically testing their theoretical proposals in the sustainable entrepreneurship field...

  11. Numeracy and sustainability

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2003-11-01

    Full Text Available Sustainable use of the planet is based on the assumption that humankind can maintain conditions suitable for inhabiting the planet indefinitely. No robust evidence supports this assumption nor rejects it, and adequate evidence on this issue may not be available for centuries. Numeracy is the ability to use or understand numerical techniques of mathematics. Even if adequate numerical data were available, the important decisions humankind makes regarding sustainable use of the planet should not be guided by numerical information alone, such as economic numbers, but by eco- and sustainability ethics, which provides a values framework that indicates how the numbers should be used and interpreted.

  12. Strategic corporate sustainability

    DEFF Research Database (Denmark)

    Grewatsch, Sylvia; Rohrbeck, René; Madsen, Henning

    This paper aims to advance the understanding of the circumstances under which corporate sustainability (CS) pays off. On the basis of a review of 129 major papers from both the sustainability and general management literature, we discuss the development of the research field. In addition we discuss...... antecedents and outcomes. To overcome this limitation we propose an integrated typology which may facilitate more research on the link between corporate sustainability performance (CSP) and corporate financial performance (CFP). Our expectation is that the strategy type might play a moderating or mediating...

  13. Sustainability in Materials Education

    Science.gov (United States)

    Fergus, Jeffrey W.; Twigge-Molecey, Christopher; Mcguffin-Cawley, James

    2013-08-01

    Consideration of the environmental and societal impacts of engineering products and processes is becoming increasingly important, so sustainability-related issues need to be addressed in educating engineers. Awareness of sustainability issues is particularly important for materials and metallurgical scientists and engineers because they are involved in both developing processes and selecting materials with low-energy use and low environmental impact. In this article, activities at TMS to identify sustainability-related educational needs and opportunities to address these needs will be discussed.

  14. Sustainable Facilities Management

    DEFF Research Database (Denmark)

    Nielsen, Susanne Balslev; Elle, Morten; Hoffmann, Birgitte

    2004-01-01

    The Danish public housing sector has more than 20 years of experience with sustainable facilities management based on user involvement. The paper outlines this development in a historical perspective and gives an analysis of different approaches to sustainable facilities management. The focus...... is on the housing departments and strateies for the management of the use of resources. The research methods used are case studies based on interviews in addition to literature studies. The paper explores lessons to be learned about sustainable facilities management in general, and points to a need for new...

  15. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...

  16. Sustaining Participatory Design Initiatives

    DEFF Research Database (Denmark)

    Iversen, Ole Sejer; Dindler, Christian

    2014-01-01

    While many participatory design (PD) projects succeed in establishing new organisational initiatives or creating technology that is attuned to the people affected, the issue of how such results are sustained after the project ends remains an important challenge. We explore the challenge...... these various forms of sustainability may be pursued in PD practice and how they can become a resource in reflecting on PD activities. Finally, we discuss implications for PD practice, suggesting that a nuanced conception of sustainability and how it may relate to PD practice are useful resources for designers...... and researchers before, during and after design processes. View full text Download full text...

  17. Sustainable Enterprise Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Williams, Joseph; Eskildsen, Jacob Kjær

    Sustainable Enterprise Excellence balances complementary and competing interests of key stakeholder segments, including society and the natural environment and increases the likelihood of superior and sustainable competitive positioning and hence long-term enterprise success that is defined...... by continuously relevant and responsible governance, strategy, actions and performance consistent with high-level organizational resilience, robustness and resplendence (R3). This is accomplished through organizational design and function emphasizing innovation, enterprise intelligence & analytics, operational......, supply chain, customer-related, human capital, financial, marketplace, societal, and environmental performance. Sustainable Enterprise Excellence integrates ethical, efficient and effective (E3) enterprise governance with 3E (equity, ecology, economy) Triple Top Line strategy throughout enterprise...

  18. Experience and Sustainable Consumption

    DEFF Research Database (Denmark)

    Rasmussen, Tove Arendt

    2014-01-01

    . Very often, however, the actual purchase does not live up to the demands of doing good in the sustainable consumption chain, and the individual might end up with a guilty conscience, which again is a possible trigger for lingering in a sentimental mode of guilt. Emotions of sentimentality may actually......Experience understood as experience-based consumption is by now fairly absent from the research agenda of the different theories on sustainable consumption. On the basis of Colin Campbell’s notion of romantic ethics and emotional sentimentality in modern hedonism, I claim that sustainable...

  19. Experience and Sustainable Consumption

    DEFF Research Database (Denmark)

    Rasmussen, Tove Arendt

    . Very often, however, the actual purchase does not live up to the demands of doing good in the sustainable consumption chain, and the individual might end up with a guilty conscience, which again is a possible trigger for lingering in a sentimental mode of guilt. Emotions of sentimentality may actually......Experience understood as experience-based consumption is by now fairly absent from the research agenda of the different theories on sustainable consumption. On the basis of Colin Campbell’s notion of romantic ethics and emotional sentimentality in modern hedonism, I claim that sustainable...

  20. Nuclear Proliferation and Authority in World Politics

    Directory of Open Access Journals (Sweden)

    Brian Frederking

    2009-11-01

    Full Text Available We apply the “security-hierarchy paradox” to nuclear proliferation. Global security requires a certain amount of hierarchy. A world in which no nuclear proliferation rules exist to constrain states, for example, would not be secure. Global security requires legitimate and authoritative rules, which we define as rules that are mutually negotiated, binding to all andwhich provide a stable social order. Too much hierarchy, however, amounts to coercion andundermines global security. Rules that are not mutually negotiated, binding to all or do not provide a stable social order are not authoritative. We argue that North Korea and Iran haveattempted to build nuclear weapons because they interpret the proliferation rules to lack authority. The coercive U.S. approaches to enforcing proliferation rules – including diplomatic isolation, preemption, and regime change – have undermined the legitimacy of those rules. When the U.S. pursues less hierarchical policies, as it has recently toward North Korea, the ensuing negotiations have facilitated progress toward an agreement. When theU.S. pursues a consistently hierarchical approach, as it has toward Iran, no progress is made. Our analysis suggests that it is worth attempting a less hierarchical approach toward Iran and encourage it to accept a deal similar to the one negotiated with North Korea.

  1. Does programmed CTL proliferation optimize virus control?

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Thomsen, Allan Randrup

    2005-01-01

    CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferati...

  2. The Global Chilling Effects of Antidumping Proliferation

    NARCIS (Netherlands)

    Vandenbussche, H.; Zanardi, M.

    2006-01-01

    Advocates of antidumping (AD) laws downplay their effects by arguing that the trade flows that are subject to AD are small and their distortions negligible.This paper is the first to counter that notion by quantifying the worldwide effect of AD laws on aggregate trade flows.The recent proliferation

  3. Luteoloside Inhibits Proliferation of Human Chronic Myeloid ...

    African Journals Online (AJOL)

    Purpose: To investigate the effects of luteoloside on the proliferation of human chronic myeloid leukemia K562 cells and whether luteoloside induces cell cycle arrest and apoptosis in K562 cells. Methods: Luteoloside's cytotoxicity was assessed using a cell counting kit. Cell cycle distribution was analysed by flow cytometry ...

  4. Nuclear war, nuclear proliferation, and their consequences

    Energy Technology Data Exchange (ETDEWEB)

    Sanruddin, A.K.

    1986-01-01

    The proceedings of a colloquium convened by the Groupe de Bellerive offers the contributions of Carl Sagan, Gabriel Garcia Marquez, Kenneth Galbraith, Pierre Trudeau, Edward Kennedy, and other eminent scientists, politicians, and strategists on the subject of the proliferation of nuclear weaponry and its potential ramifications.

  5. [Humoral regulation of stem cell proliferation].

    Science.gov (United States)

    Musashi, M; Ogawa, M

    1991-05-01

    The central feature of hematopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The recruitment of the dormant stem cells into cell cycle may be promoted by such factors as interleukin (IL)-1, IL-6, granulocyte-colony stimulating factor (G-CSF), and newly discovered IL-11. The effects of IL-1 on stem cells may be indirect. Once the stem cells leave Go and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. Though several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a stochastic process. The proliferation of early hemopoietic progenitors requires the presence of IL-3 and/or IL-4, and the intermediate process appears to be supported by granulocyte/macrophage-CSF (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin (erythropoiesis), G-CSF (neutrophil production), and IL-5 (eosinophilopoiesis). Thus, hemopoietic proliferation appears to be regulated by a cascade of factors directed at different developmental stages.

  6. Fibrosarcoma in bizarre parosteal osteochondromatous proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J.H.; Gu, M.J.; Kim, M.J.; Choi, W.H. [Dept. of Pathology, College of Medicine, Yeungnam Univ. (Korea); Shin, D.S. [Dept. of Orthopedic Surgery, College of Medicine, Yeungnam Univ. (Korea); Cho, K.H. [Dept. of Diagnostic Radiology, College of Medicine, Yeungnam Univ. (Korea)

    2001-01-01

    Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion predominantly involving the small bones of the hands and feet. Malignant transformation in BPOP has not been documented in the English literature. This report presents the coexistence of fibrosarcoma with BPOP in the right distal fibula of an 18-year-old woman. (orig.)

  7. Immunohistochemical Assessment of Proliferating Cell Nuclear ...

    African Journals Online (AJOL)

    Background: Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S‑phase of the cell cycle. ... Two sections were taken from each one for H and E. Other sections were stained according to super sensitive polymer horseradish peroxidase method for identifying PCNA expression.

  8. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increase...

  9. Transcriptional peroxisome proliferator-activated receptor γ ...

    African Journals Online (AJOL)

    user

    Peroxisome proliferator-activated receptor γ coactivator (PGC)-1ɑ, a well-known member of PGC-1 transcriptional coactivator's family, plays a key role in various metabolic pathways. Here, we investigated the role of PGC-1ɑ in the transformation of muscle fiber type in Schizothorax prenanti. The expression of PGC-1ɑ was ...

  10. Proliferation, angiogenesis and differentiation related markers in ...

    African Journals Online (AJOL)

    The upregulation of these proliferation- and angiogenesis-related factors in endothelial cells and/or fibroblasts and not in follicular cells of compact carcinoma compared to healthy glands supports the relevance of stromal cells in cancer progression. Keywords: Canine, Histology, Immunohistochemistry, Thyroid carcinoma.

  11. A sustainable woody biomass biorefinery.

    Science.gov (United States)

    Liu, Shijie; Lu, Houfang; Hu, Ruofei; Shupe, Alan; Lin, Lu; Liang, Bin

    2012-01-01

    Woody biomass is renewable only if sustainable production is imposed. An optimum and sustainable biomass stand production rate is found to be one with the incremental growth rate at harvest equal to the average overall growth rate. Utilization of woody biomass leads to a sustainable economy. Woody biomass is comprised of at least four components: extractives, hemicellulose, lignin and cellulose. While extractives and hemicellulose are least resistant to chemical and thermal degradation, cellulose is most resistant to chemical, thermal, and biological attack. The difference or heterogeneity in reactivity leads to the recalcitrance of woody biomass at conversion. A selection of processes is presented together as a biorefinery based on incremental sequential deconstruction, fractionation/conversion of woody biomass to achieve efficient separation of major components. A preference is given to a biorefinery absent of pretreatment and detoxification process that produce waste byproducts. While numerous biorefinery approaches are known, a focused review on the integrated studies of water-based biorefinery processes is presented. Hot-water extraction is the first process step to extract value from woody biomass while improving the quality of the remaining solid material. This first step removes extractives and hemicellulose fractions from woody biomass. While extractives and hemicellulose are largely removed in the extraction liquor, cellulose and lignin largely remain in the residual woody structure. Xylo-oligomers, aromatics and acetic acid in the hardwood extract are the major components having the greatest potential value for development. Higher temperature and longer residence time lead to higher mass removal. While high temperature (>200°C) can lead to nearly total dissolution, the amount of sugars present in the extraction liquor decreases rapidly with temperature. Dilute acid hydrolysis of concentrated wood extracts renders the wood extract with monomeric sugars

  12. Nuclear non proliferation and disarmament; Non-proliferation nucleaire et desarmement

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

  13. Blue light inhibits proliferation of melanoma cells

    Science.gov (United States)

    Becker, Anja; Distler, Elisabeth; Klapczynski, Anna; Arpino, Fabiola; Kuch, Natalia; Simon-Keller, Katja; Sticht, Carsten; van Abeelen, Frank A.; Gretz, Norbert; Oversluizen, Gerrit

    2016-03-01

    Photobiomodulation with blue light is used for several treatment paradigms such as neonatal jaundice, psoriasis and back pain. However, little is known about possible side effects concerning melanoma cells in the skin. The aim of this study was to assess the safety of blue LED irradiation with respect to proliferation of melanoma cells. For that purpose we used the human malignant melanoma cell line SK-MEL28. Cell proliferation was decreased in blue light irradiated cells where the effect size depended on light irradiation dosage. Furthermore, with a repeated irradiation of the melanoma cells on two consecutive days the effect could be intensified. Fluorescence-activated cell sorting with Annexin V and Propidium iodide labeling did not show a higher number of dead cells after blue light irradiation compared to non-irradiated cells. Gene expression analysis revealed down-regulated genes in pathways connected to anti-inflammatory response, like B cell signaling and phagosome. Most prominent pathways with up-regulation of genes were cytochrome P450, steroid hormone biosynthesis. Furthermore, even though cells showed a decrease in proliferation, genes connected to the cell cycle were up-regulated after 24h. This result is concordant with XTT test 48h after irradiation, where irradiated cells showed the same proliferation as the no light negative control. In summary, proliferation of melanoma cells can be decreased using blue light irradiation. Nevertheless, the gene expression analysis has to be further evaluated and more studies, such as in-vivo experiments, are warranted to further assess the safety of blue light treatment.

  14. Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

    NARCIS (Netherlands)

    Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

    BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

  15. Sovereignty, individuality, and sustainability

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2003-09-01

    Full Text Available Humans must acknowledge that the biosphere is the essential support for all living organisms. In order to achieve sustainable use of the planet, humans must proceed beyond egocentrism, ethnocentrism, homocentrism, and biocentrism to ecocentrism. National states, with present policies, are a major obstacle to sustainable use of the planet. However, there is some evidence that the individual has increasing sovereignty at the expense of both nation states and the environment. Still, the primary obstacle to sustainability is inherent in the present system of sovereign nation states. The basic question is how much sovereignty must nation-states and individuals relinquish to preserve the health of Earth's biospheric life support system. A free and open exchange of thoughts on this subject is long overdue. To acheive sustainable use of the planet, humankind must view its identity within the context of the interdependent web of life.

  16. Sustainable Practices Innovation

    Science.gov (United States)

    Better sustainability means more environmentally conscious and efficient businesses and communities. EPA helps modify the way we consume energy, deal with waste, and grow our economy through programs such as Energy Star, E3, Smart Growth, and WaterSense.

  17. The Sustainable City.

    Science.gov (United States)

    Gangloff, Deborah

    1995-01-01

    Focuses on methods to make cities more sustainable through the processes of energy efficiency, pollution and waste reduction, capture of natural processes, and the merger of ecological, economic, and social factors. (LZ)

  18. Sustainable roadway lighting seminar.

    Science.gov (United States)

    2014-07-01

    The objective of this project was to develop and conduct a half-day educational seminar on sustainable : roadway lighting at three locations within New York State: Rochester, New York City, and Albany. : Primary attendees were engineers from the New ...

  19. Sustainable Enterprise Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick

    2013-01-01

    Structured Abstract Purpose: Sustainable Enterprise Excellence (SEE) is defined and developed through integration and expansion of business excellence modeling and sustainability thought. The intent is to enable simple yet reliable enterprise assessment of triple bottom line (TBL) performance...... and produce actionable enterprise foresight that can enable next best practices and sources of sustainable competitive advantage through innovation. Methodology: Key elements of SEE are identified from various business excellence and sustainability reporting sources, including the Global Reporting Initiative...... assessment approach similar in structure to those behind established excellence awards are developed that enable enterprise assessment of progress toward SEE. The resulting assessment is delivered in a highly consumable, combined narrative and graphic format referred to as a SEE NEWS Report. Practical...

  20. Strategic sustainability performance plan

    Science.gov (United States)

    2010-06-01

    In October 2009, President Obama signed Executive Order (EO) 13514 that sets sustainability : goals for Federal agencies and focuses on making improvements in environmental, energy and : economic performance. The Executive Order requires Federal agen...

  1. Transport, environment and sustainability

    DEFF Research Database (Denmark)

    Joumard, Robert; Gudmundsson, Henrik; Kehagia, Fotini

    2010-01-01

    This report is the final report of the action COST 356 'EST - Towards the definition of a measurable environmentally sustainable transport'. It tries to answer the following questions: How can environmental impacts of transport be measured? How can measurements be transformed into operational...... indicators? How can several indicators be jointly considered? And how can indicators be used in planning and decision making? Firstly we provide definition of 'indicator of environmental sustainability in transport'. The functions, strengths and weaknesses of indicators as measurement tools, and as decision...... support tools are discussed. We define what "environmental sustainability in transport" may mean through the transport system, the concepts of sustainable development and of environment. The concept of 'chain of causality' between a source and a final target is developed, as a common reference...

  2. Sustainability Principles in Practice

    DEFF Research Database (Denmark)

    Gani, Rafiqul; Wenzel, Henrik; Azapagic, Adisa

    2007-01-01

    generation, transport, heating and cooling, on the other hand, it has a considerable impact on the environment, via its resource consumption, its emissions and the impact of its products. New (sustainable) alternatives, for example, change of raw material base, use of renewable resources, efficient...... manufacture of chemical products and sustainable products and processes that can efficiently manufacture them, will need to be considered to meet the current and future challenges. Some of the important issues in this respect are how to generate/identify sustainable alternatives, how to analyze them, which...... criteria should be used to evaluate them, and how to implement them? The objective of this presentation is to highlight the use of systematic multidisciplinary approaches for generation of sustainable alternatives combined with methods/tools for analysis and evaluation. For generation of alternatives...

  3. Biorefinery Sustainability Analysis

    DEFF Research Database (Denmark)

    J. S. M. Silva, Carla; Prunescu, Remus Mihail; Gernaey, Krist

    2017-01-01

    This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system and of t......This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system...... and of the biorefinery-based system. Socio-economic criteria and indicators used in sustainability frameworks assessment are presented and discussed. There is not one single methodology that can aptly cover the synergies of environmental, economic, social and governance issues required to assess the sustainable...

  4. Social Health and Sustainability

    DEFF Research Database (Denmark)

    Andersen, Heidi Lene

    2015-01-01

    Abstract: This article discusses how to accomplish a transition towards healthy and sustainable futures. Despite political statements and profound theoretical developments, little has happened in the field of practice. This article presents a number of problematics in the theoretical and conceptual...... development within the fields of sustainability and health promotion. With this objective in mind, this article seeks to find solutions to a question raised by the WHO health and sustainability researcher, Illona Kickbusch: ‘What conceptual framing and common language can help move a shared agenda forward...... departments. The article demonstrates that an action research approach including an Aristotelean phronetic perspective can be successful in integrating health and sustainability in research, as well as in practice. There are two main conclusions from the empirical case study. The first is that the common...

  5. Crowdfunding for Sustainability

    DEFF Research Database (Denmark)

    Nielsen, Kristian Roed

    The dissertation sets out to explore the often ignored role of the consumer (end-user) within sustainable innovation by examining the potential of reward-based crowdfunding in enabling sustainable entrepreneurship. It explores under which conditions and to what extent rewardbased crowdfunding could...... benefit entrepreneurs with social and/or environmentally-oriented products. The dissertation employs four articles in order to explore this. The first sets the stage by systematically reviewing the various roles that end-users can adopt within sustainable innovation process. The second serves to present...... access, while paper four introduces the experimental evidence on the role of individual and product details in shaping pledging behavior as it relates to a diversity of (un)sustainable campaigns....

  6. Life Cycle Sustainability Dashboard

    DEFF Research Database (Denmark)

    Traverso, Marzia; Finkbeiner, Matthias; Jørgensen, Andreas

    2012-01-01

    One method to assess the sustainability performance of products is life cycle sustainability assessment (LCSA), which assesses product performance considering the environmental,economic, and social dimensions of the life cycle. The results of LCSA can be used to compare different products...... or to support decision making toward sustainable production and consumption. In both cases, LCSA results could be too disaggregated and consequently too difficult to understand and interpret by decision makers. As non-experts are usually the target audience of experts and scientists, and are also involved...... in decision-making processes, the necessity for a straightforward but comprehensive presentation of LCSA results is becoming strategically important. The implementation of the dashboard of sustainability proposed in this article offers a possible solution. An outstanding characteristic of the dashboard...

  7. Sustainable advanced construction technologies

    CSIR Research Space (South Africa)

    Kuchena, JC

    2009-11-01

    Full Text Available Advanced Construction Technologies (ACTs) are set to become the sustainable mainstay of the construction industry due to the demand for innovative housing solutions. Like most emerging economies, South Africa from a historical perspective and global...

  8. Sustainable Materials Management

    Science.gov (United States)

    To introduce businesses, NGOs, and government officials to the concept of Sustainable Materials Management (SMM). To provide tools to allow stakeholders to take a lifecycle approach managing their materials, & to encourage them to join a SMM challenge.

  9. Packaging for Sustainability

    CERN Document Server

    Lewis, Helen; Fitzpatrick, Leanne

    2012-01-01

    The packaging industry is under pressure from regulators, customers and other stakeholders to improve packaging’s sustainability by reducing its environmental and societal impacts. This is a considerable challenge because of the complex interactions between products and their packaging, and the many roles that packaging plays in the supply chain. Packaging for Sustainability is a concise and readable handbook for practitioners who are trying to implement sustainability strategies for packaging. Industry case studies are used throughout the book to illustrate possible applications and scenarios. Packaging for Sustainability draws on the expertise of researchers and industry practitioners to provide information on business benefits, environmental issues and priorities, environmental evaluation tools, design for environment, marketing strategies, and challenges for the future.

  10. The macroecology of sustainability

    Science.gov (United States)

    Burger, Joseph R.; Allen, Craig D.; Brown, James H.; Burnside, William R.; Davidson, Ana D.; Fristoe, Trevor S.; Hamilton, Marcus J.; Mercado-Silva, Norman; Nekola, Jeffrey C.; Okie, Jordan G.; Zuo, Wenyun

    2012-01-01

    The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.

  11. Food, Globalization and Sustainability

    NARCIS (Netherlands)

    Oosterveer, P.J.M.; Sonnenfeld, D.A.

    2011-01-01

    Food is increasingly traded internationally, thereby transforming the organisation of food production and consumption globally and influencing most food-related practices. This transition is generating unfamiliar challenges related to sustainability of food provision, the social impacts of

  12. The macroecology of sustainability.

    Science.gov (United States)

    Burger, Joseph R; Allen, Craig D; Brown, James H; Burnside, William R; Davidson, Ana D; Fristoe, Trevor S; Hamilton, Marcus J; Mercado-Silva, Norman; Nekola, Jeffrey C; Okie, Jordan G; Zuo, Wenyun

    2012-01-01

    The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.

  13. Sustainable investment: Literature overview

    NARCIS (Netherlands)

    Weda, J.; Kerste, M.; Rosenboom, N.

    2010-01-01

    Corporate Social Responsibility (CSR), or sustainability at the company level, entails incorporating ecological (environmental stakeholders) and social aspects (stakeholders other than shareholders and environmental stakeholders) when doing business. Socially Responsible Investment (SRI) concerns

  14. Regional Sustainable Environmental Management

    Science.gov (United States)

    Regional sustainable environmental management is an interdisciplinary effort to develop a sufficient understanding of the interactions between ecosystems, the economy, law, and technology to formulate effective long-term management strategies on a regional scale. Regional sustai...

  15. Towards Intelligently - Sustainable Cities?

    Directory of Open Access Journals (Sweden)

    Luca Salvati

    2013-04-01

    Full Text Available In the quest for achieving sustainable cities, Intelligent and Knowledge City Programmes (ICPs and KCPs represent cost-efficient strategies for improving the overall performance of urban systems. However, even though nobody argues on the desirability of making cities “smarter”, the fundamental questions of how and to what extent can ICPs and KCPs contribute to the achievement of urban sustainability lack a precise answer. In the attempt of providing a structured answer to these interrogatives, this paper presents a methodology developed for investigating the modalities through which ICPs and KCPs contribute to the achievement or urban sustainability. Results suggest that ICPs and KCPs efficacy lies in supporting cities achieve a sustainable urban metabolism through optimization, innovation and behavior changes.

  16. Sustaining Success in Haiti

    National Research Council Canada - National Science Library

    Oakley, Robert

    1996-01-01

    ... irreversible. The next several months are critical. Sustaining the success of Operation Uphold Democracy requires Haiti--and the international community--to confront, simultaneously, crucial transitions in political leadership, law and order, economic...

  17. Transgovernance: advancing sustainability governance

    National Research Council Canada - National Science Library

    Meuleman, Louis

    2013-01-01

    ... – together characterized as the emergence of a knowledge democracy – may imply for governance for sustainable development, on global and other levels of societal decision making, and the other way around...

  18. Commons, Sustainability, Democratization

    DEFF Research Database (Denmark)

    In nine chapters practical-conceptual drafts of action reserach in relation to sustainability are presented and examples of action research in Scandinavia, England, Nicaragua and Mozambique are described and analyzed....

  19. CCL2/MCP-1 modulation of microglial activation and proliferation

    Directory of Open Access Journals (Sweden)

    Garcia-Bueno Borja

    2011-07-01

    Full Text Available Abstract Background Monocyte chemoattractant protein (CCL2/MCP-1 is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Methods Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU. Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. Results MCP-1 treatment (50 ng/ml, 24 h did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α, either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2 expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. Conclusion These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be

  20. 2005 Environmental Sustainability Index (ESI)

    Data.gov (United States)

    National Aeronautics and Space Administration — The 2005 Environmental Sustainability Index (ESI) is a measure of overall progress towards environmental sustainability, developed for 146 countries. The index...

  1. Involving citizens in sustainable development

    DEFF Research Database (Denmark)

    Agger, Annika

    2010-01-01

    Local Environment The International Journal of Justice and Sustainability, Volume 15 Issue 6, 541......Local Environment The International Journal of Justice and Sustainability, Volume 15 Issue 6, 541...

  2. 2002 Environmental Sustainability Index (ESI)

    Data.gov (United States)

    National Aeronautics and Space Administration — The 2002 Environmental Sustainability Index (ESI) measures overall progress toward environmental sustainability for 142 countries based on environmental systems,...

  3. Genuine savings and sustainability

    OpenAIRE

    Hanley, Nicholas David; Dupuy, Louis Paul; MCLAUGHLIN, Eoin

    2015-01-01

    Genuine Savings has emerged as the leading economic indicator of sustainable economic development at the country level. It derives from the literatures on weak sustainability, wealth accounting and national income accounting. We discuss the theoretical underpinnings of GS, focusing on the relationship between changes in a nation's extended capital stock and the future path of consumption. The indicator has entered widespread use propelled by the World Bank's publications, despite its varying ...

  4. Leadership for Sustainable Installations

    Science.gov (United States)

    2011-04-01

    able_installations/. Accessed 15 April 2011) Leadership for Sustainable Installations By COL Charles Allen (Ret), U.S. Army War College The...number. 1. REPORT DATE APR 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Leadership for Sustainable...of the Army civilian workforce. During that decade, we followed the mandate of A-76 Commercial Sourcing and focused on developing the Most Efficient

  5. Settlement patterns and sustainability

    DEFF Research Database (Denmark)

    Hendriksen, Kåre

    This paper discusses settlement patterns and sustainability. Generally urbanization is recognised as an inevitable development driven by job opportunities, better service supply, education, and health services, and it is argued that this is the main driver for centralisation. Research based...... of utilization of local resources and trade opportunities. Furthermore the growing towns are struggling with an un-sustainable economic situation manly based on public financed jobs or welfare payments and with limited export oriented value creation....

  6. Innovating for sustainability

    DEFF Research Database (Denmark)

    The theme of the articles is innovating for sustainability. Empirically the articles shows how enterprises makes environmental innovations related to their processes and products within the organic dairy industry, the fish processing industry and the car industry.......The theme of the articles is innovating for sustainability. Empirically the articles shows how enterprises makes environmental innovations related to their processes and products within the organic dairy industry, the fish processing industry and the car industry....

  7. Agroecology and Sustainable Agriculture

    OpenAIRE

    Fabio Caporali

    2007-01-01

    In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006), a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. ...

  8. Assembling Sustainable Territories

    DEFF Research Database (Denmark)

    Vandergeest, Peter; Ponte, Stefano; Bush, Simon

    2015-01-01

    The authors show how certification assembles ‘sustainable’ territories through a complex layering of regulatory authority in which both government and nongovernment entities claim rule-making authority, sometimes working together, sometimes in parallel, sometimes competitively. It is argued...... dynamic in assembling sustainable territories, and that certification always involves state agencies in determining how the key elements that comprise it are defined. Whereas some state agencies have been suspicious of sustainability certification, others have embraced it or even used it to extend...

  9. Seeking sustainability leadership

    OpenAIRE

    Bendell, Jem; Little, Richard

    2015-01-01

    This paper critiques mainstream leadership and leadership development approaches to help inform the emerging field of sustainability leadership. Traditional leadership theory and education is argued to be highly problematic for the pursuit of sustainability leadership. A more critical approach is required, drawing upon insights from social theory, critical discourse analysis and psychology, which is attempted in this paper. Once deconstructed, leadership can be a useful framework for explorin...

  10. SUSTAINABLE TRAILER FLOORING

    OpenAIRE

    John Lu; Marc Chorney; Lowell Peterson

    2009-01-01

    Different trailer flooring materials, including wood-based, aluminum, steel, and synthetic plastic floors, were evaluated in accordance with their durability and sustainability to our natural environment. Wood-based trailer flooring is an eco-friendly product. It is the most sustainable trailer flooring material compared with fossil fuel-intensive steel, aluminum, and plastics. It is renewable and recyclable. Oak, hard maple, and apitong are strong and durable hardwood species that are curren...

  11. A sustainable economy

    OpenAIRE

    Pawlak, J. J.

    2008-01-01

    There exists a direct correlation between improvements in standard of living and the consumption of resources. To be able to maintain the standard of living of a modern developed country, society must adapt to an economy based on sustainable processes, energy, and raw materials. The sustainable economy presents itself as a disruptive technology to the traditional economy, which is based largely on non-renewable resources. The issue seems to be more about when will we switch to a sustainabl...

  12. Predicting sustainable work behavior

    OpenAIRE

    Sundtoft Hald, Kim

    2013-01-01

    Sustainable work behavior is an important issue for operations managers – it has implications for most outcomes of OM. This research explores the antecedents of sustainable work behavior. It revisits and extends the sociotechnical model developed by Brown et al. (2000) on predicting safe behavior. Employee characteristics and general attitudes towards safety and work condition are included in the extended model. A survey was handed out to 654 employees in Chinese factories. This research ...

  13. Sustainability of National Cohesion

    Directory of Open Access Journals (Sweden)

    Andrei Mihai Cristea

    2013-09-01

    Full Text Available In the European Union, cohesion policy is the third country after the domestic and social policy, as this policy is a tool for economic growth and also a balancing factor. Through its solidarity funds contribute to the other sectorial policies: the Common Agricultural Policy, social policy, environmental policy. This article aims to demonstrate the importance of cohesion policy in the national economy and how to improve its implementation by ensuring sustainable development and sustainable economic growth

  14. Sustainability, accounting and reporting

    CERN Document Server

    Balachandran, Kashi

    2011-01-01

    The topic of business sustainability is multidisciplinary in nature, and its complexity calls for putting in place a wide variety of research approaches, such as action research, case studies, surveys, model development etc. The papers presented in this ebook represent a comprehensive overview of recent advances in this area of accounting and reporting research. It contains six papers, covering how leasing can increase environmental benefits, CSR, developing social, environmental and economic indicators for SMEs, sustainability reporting and reputation risk and others.

  15. Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc.

    Science.gov (United States)

    Femia, Angelo Pietro; Luceri, Cristina; Soares, Paulo Victoria; Lodovici, Maura; Caderni, Giovanna

    2015-03-15

    PIRC rats (F344/NTac-Apc (am1137) ) mutated in the Apc gene spontaneously develop colon tumors thus mimicking familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC) more closely than Apc-based rodent models developing tumors mostly in the small intestine. To understand whether microscopic dysplastic lesions precede the development of macroscopic tumors, PIRC rat colon was examined for the presence of mucin depleted foci (MDF), microadenomas of the rodent and human colon. Few MDF (about 4/animal) were already present in 1-month-old rats and their number rapidly increases to about 250 in 8-month-old rats. These lesions showed Wnt signaling activation (nuclear β-catenin accumulation) and were dramatically decreased by sulindac (320 ppm), a drug with chemopreventive activity (MDF/rat at 4 months: 156 ± 8 and 38 ± 6 in controls and sulindac-treated rats, respectively, means ± SE, p rats. Colon proliferation (PCNA expression) was significantly higher in PIRC rats. Notably, PIRC rat NM showed resistance to apoptosis since it sustained proliferation and had lower apoptosis after a cytotoxic insult with 1,2 dimethylhydrazine. Gene expression of Myc, p21, Birc5, Ogg1, Apex1 and Sod2 were significantly up-regulated in the NM of PIRC rat. The overall results put forward PIRC rat as useful model of colon carcinogenesis, either to study the process itself or to test in vivo chemopreventive agents in both short- and long-term studies. © 2014 UICC.

  16. Thorium-based fuel cycles: Reassessment of fuel economics and proliferation risk

    Energy Technology Data Exchange (ETDEWEB)

    Serfontein, Dawid E., E-mail: Dawid.Serfontein@nwu.ac.za [Senior Lecturer at the School of Mechanical and Nuclear Engineering, North West University (PUK-Campus), PRIVATE BAG X6001, Internal Post Box 360, Potchefstroom 2520 (South Africa); Mulder, Eben J. [Professor at the School of Mechanical and Nuclear Engineering, North West University (South Africa)

    2014-05-01

    At current consumption and current prices, the proven reserves for natural uranium will last only about 100 years. However, the more abundant thorium, burned in breeder reactors, such as large High Temperature Gas-Cooled Reactors, and followed by chemical reprocessing of the spent fuel, could stretch the 100 years for uranium supply to 15,000 years. Thorium-based fuel cycles are also viewed as more proliferation resistant compared to uranium. However, several barriers to entry caused all countries, except India and Russia, to abandon their short term plans for thorium reactor projects, in favour of uranium/plutonium fuel cycles. In this article, based on the theory of resonance integrals and original analysis of fast fission cross sections, the breeding potential of {sup 232}Th is compared to that of {sup 238}U. From a review of the literature, the fuel economy of thorium-based fuel cycles is compared to that of natural uranium-based cycles. This is combined with a technical assessment of the proliferation resistance of thorium-based fuel cycles, based on a review of the literature. Natural uranium is currently so cheap that it contributes only about 10% of the cost of nuclear electricity. Chemical reprocessing is also very expensive. Therefore conservation of natural uranium by means of the introduction of thorium into the fuel is not yet cost effective and will only break even once the price of natural uranium were to increase from the current level of about $70/pound yellow cake to above about $200/pound. However, since fuel costs constitutes only a small fraction of the total cost of nuclear electricity, employing reprocessing in a thorium cycle, for the sake of its strategic benefits, may still be a financially viable option. The most important source of the proliferation resistance of {sup 232}Th/{sup 233}U fuel cycles is denaturisation of the {sup 233}U in the spent fuel by {sup 232}U, for which the highly radioactive decay chain potentially poses a large

  17. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I......Bacteria can avoid extinction during antimicrobial exposure by becoming resistant. They achieve this either via adaptive mutations or horizontally acquired resistance genes. If resistance emerges in clinical relevant species, it can lead to treatment failure and ultimately result in increasing...... morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...

  18. Sustainability of abrasive processes

    DEFF Research Database (Denmark)

    Aurich, J.C.; Linke, B.; Hauschild, Michael Zwicky

    2013-01-01

    This paper presents an overview of research on sustainability of abrasive processes. It incorporates results from a round robin study on ‘‘energy-efficiency of abrasive processes’’ which has been carried out within the scientific technical committee ‘‘abrasive processes’’ (STC G) of CIRP, the con......This paper presents an overview of research on sustainability of abrasive processes. It incorporates results from a round robin study on ‘‘energy-efficiency of abrasive processes’’ which has been carried out within the scientific technical committee ‘‘abrasive processes’’ (STC G) of CIRP......, the content of technical presentations in STC G, and the results of a comprehensive literature study. The approach to sustainability includes environmental, social, and economic sustainability in accordance with the definition proposed in the Brundtland Report of the United Nations [156]. The main focus...... is on environmental and social sustainability. Economic sustainability will be considered as manufacturing productivity. © 2013 CIRP....

  19. Sustainability at BPA 2013

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    THIS IS THE THIRD YEAR BPA has reported on sustainability program accomplishments. The report provides an opportunity to review progress made on sustainability initiatives, evaluate how far we have come and how much we can improve. The program has demonstrated maturation as the concepts of sustainability and resource conservation are communicated and understood. The sustainability program started as an employee-driven “grass roots” effort in 2010. Sustainability is becoming a consideration in how work is performed. The establishment of several policies supporting sustainability efforts proves the positive progress being made. In 2009, BPA became a founder and member of The Climate Registry, a nonprofit collaboration that sets standards to calculate, verify and report greenhouse gas emissions. This year, BPA completed and published our Greenhouse Gas inventory for the years of 2009, 2010 and 2011. The 2012 inventory is currently in the process of third-party verification and scheduled for public release in January 2014. These inventories provide a concrete measure of the progress we are making.

  20. Sustainable Biofuels Development Center

    Energy Technology Data Exchange (ETDEWEB)

    Reardon, Kenneth F. [Colorado State Univ., Fort Collins, CO (United States)

    2015-03-01

    The mission of the Sustainable Bioenergy Development Center (SBDC) is to enhance the capability of America’s bioenergy industry to produce transportation fuels and chemical feedstocks on a large scale, with significant energy yields, at competitive cost, through sustainable production techniques. Research within the SBDC is organized in five areas: (1) Development of Sustainable Crops and Agricultural Strategies, (2) Improvement of Biomass Processing Technologies, (3) Biofuel Characterization and Engine Adaptation, (4) Production of Byproducts for Sustainable Biorefining, and (5) Sustainability Assessment, including evaluation of the ecosystem/climate change implication of center research and evaluation of the policy implications of widespread production and utilization of bioenergy. The overall goal of this project is to develop new sustainable bioenergy-related technologies. To achieve that goal, three specific activities were supported with DOE funds: bioenergy-related research initiation projects, bioenergy research and education via support of undergraduate and graduate students, and Research Support Activities (equipment purchases, travel to attend bioenergy conferences, and seminars). Numerous research findings in diverse fields related to bioenergy were produced from these activities and are summarized in this report.

  1. Social Sciences and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available At the time when the journal Sustainability [1] was launched, as a chemist and a scientist, I started to believe that social sciences may be more important to make humans sustainable. The broad journal title Social Sciences presents the opportunity for all social science scholars to have integrated consideration regarding the sustainability of humanity, because I am sure that science and technology alone cannot help. Science and technology may have in fact been contributing to accelerate the depletion of nonrenewable natural resources and putting human sustainability at risk since the industrial revolution about 150 years ago. I hope all intellectuals studying anthropology, archaeology, administration, communication, criminology, economics, education, government, linguistics, international relations, politics, sociology and, in some contexts, geography, history, law, and psychology publish with us to seek a solution to sustain humanity. Sustainability itself will also be a main topic of the journal Social Sciences. In addition to this integrated forum for social sciences, more topic specific journals, such as the already publishing Societies [2], will be launched. [...

  2. Sustainable Water Systems

    Directory of Open Access Journals (Sweden)

    Miklas Scholz

    2013-02-01

    Full Text Available Sustainable water systems often comprise complex combinations of traditional and new system components that mimic natural processes. These green systems aim to protect public health and safety, and restore natural and human landscapes. Green infrastructure elements such as most sustainable drainage systems trap storm water but may contaminate groundwater. There is a need to summarize recent trends in sustainable water systems management in a focused document. The aim of this special issue is therefore to disseminate and share scientific findings on novel sustainable water systems addressing recent problems and opportunities. This special issue focuses on the following key topics: climate change adaptation and vulnerability assessment of water resources systems; holistic water management; carbon credits; potable water savings; sustainable water technologies; nutrient management; holistic storm water reuse; water and wastewater infrastructure planning; ecological status of watercourses defined by the Water Framework Directive. The combined knowledge output advances the understanding of sustainable water, wastewater and storm water systems in the developed and developing world. The research highlights the need for integrated decision-support frameworks addressing the impact of climate change on local and national water resources management strategies involving all relevant stakeholders at all levels.

  3. Biofuels and sustainability.

    Science.gov (United States)

    Solomon, Barry D

    2010-01-01

    Interest in liquid biofuels production and use has increased worldwide as part of government policies to address the growing scarcity and riskiness of petroleum use, and, at least in theory, to help mitigate adverse global climate change. The existing biofuels markets are dominated by U.S. ethanol production based on cornstarch, Brazilian ethanol production based on sugarcane, and European biodiesel production based on rapeseed oil. Other promising efforts have included programs to shift toward the production and use of biofuels based on residues and waste materials from the agricultural and forestry sectors, and perennial grasses, such as switchgrass and miscanthus--so-called cellulosic ethanol. This article reviews these efforts and the recent literature in the context of ecological economics and sustainability science. Several common dimensions for sustainable biofuels are discussed: scale (resource assessment, land availability, and land use practices); efficiency (economic and energy); equity (geographic distribution of resources and the "food versus fuel" debate); socio-economic issues; and environmental effects and emissions. Recent proposals have been made for the development of sustainable biofuels criteria, culminating in standards released in Sweden in 2008 and a draft report from the international Roundtable on Sustainable Biofuels. These criteria hold promise for accelerating a shift away from unsustainable biofuels based on grain, such as corn, and toward possible sustainable feedstock and production practices that may be able to meet a variety of social, economic, and environmental sustainability criteria.

  4. Global sustainability: Toward definition

    Science.gov (United States)

    Brown, Becky J.; Hanson, Mark E.; Liverman, Diana M.; Merideth, Robert W.

    1987-11-01

    Sustainability is increasingly viewed as a desired goal of development and environmental management. This term has been used in numerous disciplines and in a variety of contexts, ranging from the concept of maximum sustainable yield in forestry and fisheries management to the vision of a sustainable society with a steady-state economy. The meaning of the term is strongly dependent on the context in which it is applied and on whether its use is based on a social, economic, or ecological perspective, Sustainability may be defined broadly or narrowly, but a useful definition must specify explicitly the context as well as the temporal and spatial scales being considered. Although societies differ in their conceptualizations of sustainability, indefinite human survival on a global scale requires certain basic support systems, which can be maintained only with a healthy environment and a stable human population. A clearer understanding of global sustainability and the development of appropriate indicators of the status of basic support systems would provide a useful framework for policy making.

  5. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  6. Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes

    Directory of Open Access Journals (Sweden)

    Smith Logan B

    2012-12-01

    Full Text Available Abstract Background Fibroblast growth factor receptor 3 (FGFR3 inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone (T3 plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase (TERT and RNA component of telomerase (TR, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity (p 3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity (p 3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions The results suggest that FGFR3 inhibits chondrocyte proliferation by down-regulating TERT expression and reducing telomerase activity indicating an important role for telomerase in sustaining chondrocyte proliferative capacity during bone elongation.

  7. Sustainable IT and IT for Sustainability

    Science.gov (United States)

    Liu, Zhenhua

    Energy and sustainability have become one of the most critical issues of our generation. While the abundant potential of renewable energy such as solar and wind provides a real opportunity for sustainability, their intermittency and uncertainty present a daunting operating challenge. This thesis aims to develop analytical models, deployable algorithms, and real systems to enable efficient integration of renewable energy into complex distributed systems with limited information. The first thrust of the thesis is to make IT systems more sustainable by facilitating the integration of renewable energy into these systems. IT represents the fastest growing sectors in energy usage and greenhouse gas pollution. Over the last decade there are dramatic improvements in the energy efficiency of IT systems, but the efficiency improvements do not necessarily lead to reduction in energy consumption because more servers are demanded. Further, little effort has been put in making IT more sustainable, and most of the improvements are from improved "engineering" rather than improved "algorithms". In contrast, my work focuses on developing algorithms with rigorous theoretical analysis that improve the sustainability of IT. In particular, this thesis seeks to exploit the flexibilities of cloud workloads both (i) in time by scheduling delay-tolerant workloads and (ii) in space by routing requests to geographically diverse data centers. These opportunities allow data centers to adaptively respond to renewable availability, varying cooling efficiency, and fluctuating energy prices, while still meeting performance requirements. The design of the enabling algorithms is however very challenging because of limited information, non-smooth objective functions and the need for distributed control. Novel distributed algorithms are developed with theoretically provable guarantees to enable the "follow the renewables" routing. Moving from theory to practice, I helped HP design and implement

  8. Sustainable Procurement: Integrating Classroom Learning with University Sustainability Programs

    Science.gov (United States)

    Goldschmidt, Kyle; Harrison, Terry; Holtry, Matthew; Reeh, Jeremy

    2013-01-01

    Organizations are facing increased pressure from various stakeholders to address issues of sustainability, resulting in a growing demand for sustainability education and training. Procurement groups remain the key drivers of many sustainability-related strategies, placing pressure on universities to integrate sustainability concepts into the…

  9. Cyclic AMP inhibition of proliferation of hepatocellular carcinoma cells is mediated by Akt.

    Science.gov (United States)

    Liu, Lunhua; Xie, Yili; Lou, Liguang

    2005-11-01

    Cyclic AMP (cAMP), one of the most important intracellular second messengers, has been reported to inhibit proliferation of human hepatocellular carcinoma (HCC) cells via negatively regulating p42/44 mitogen-activated protein kinase. Here, we reported that cAMP inhibited the proliferation of HCC BEL-7402 cells via a novel mechanism. Forskolin, an activator of adenylate cyclase, inhibited fetal bovine serum (FBS)-stimulated BEL-7402 cell proliferation in a dose- and time-dependent manner, along with the inhibition of FBS-stimulated serine/threoine protein kinase Akt (also known as PKB) phosphorylation which is required for Akt activation and this effect was mimicked by 8-Br cAMP. Forskolin also inhibited Akt phosphorylation stimulated by other growth factors such as IGF-1, epidermal growth factor, and insulin. These inhibitions were found not only in BEL-7402 cells, but also in another HCC cell line SMMC-7721 cells. Myr-Akt (myristolated-Akt), a constitutively active Akt which was relatively resistant to cAMP inhibition, conferred BEL-7402 cells resistance to cAMP treatment. However, overexpression of Myr-Akt alone was not sufficient to stimulate BEL-7402 cell proliferation. cAMP inhibited FBS-stimulated Akt phosphorylation in a cAMP-dependent protein kinase-dependent manner. Further studies demonstrated that cAMP inhibited FBS-induced membrane localization of 3-phosphoinositide-dependent kinase 1 (PDK-1) which is a required process for PDK-1 to phosphorylate Akt, but had no significant effect on phosphoinositide 3-kinase activity. These results indicate that cAMP inhibition of proliferation of HCC cells is mediated by Akt and cAMP inhibits Akt activation via blocking membrane localization of PDK-1.

  10. Creating Genetic Resistance to HIV

    Science.gov (United States)

    Burnett, John C.; Zaia, John A.; Rossi, John J.

    2012-01-01

    HIV/AIDS remains a chronic and incurable disease, in spite of the notable successes of highly active antiretroviral therapy. Gene therapy offers the prospect of creating genetic resistance to HIV that supplants the need for antiviral drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based therapeutics. Combinations of therapeutic genes against viral and host targets are designed to improve the overall antiviral potency and reduce the likelihood of viral resistance. In cell-based therapies, therapeutic genes are expressed in gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV-resistant immune system. Such strategies must promote the selective proliferation of the transplanted cells and the prolonged expression of therapeutic genes. This review focuses on the current advances and limitations in genetic therapies against HIV, including the status of several recent and ongoing clinical studies. PMID:22985479

  11. New approaches to nuclear proliferation policy.

    Science.gov (United States)

    Nye, J S

    1992-05-29

    Nuclear proliferation is not one but a complex of problems. One relates to the collapse of the Soviet Union and its effect on the spread of nuclear weapons and knowledge. Second, Iraq's violation of its Non-Proliferation Treaty obligation has exposed certain weaknesses in the traditional regime of multilateral nonproliferation institutions and treaties. Third, Pakistan's achievement of a nuclear weapons capability in the late 1980s brings the postproliferation question to the forefront in South Asia. There is no single solution to this complex set of problems, but the beginning of wisdom is to build upon the successes of the past, add new policy procedures, and, above all, increase the priority given to the issue. Otherwise, we may be faced with the ironic outcome that the widely welcomed end of the Cold War may increase the prospect of nuclear use.

  12. XIAP antagonist embelin inhibited proliferation of cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Cody J Wehrkamp

    Full Text Available Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL. However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis.

  13. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1994-10-17

    This series is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. Essays contained in this document include: Key issues on NPT renewal and extension, Africa and nuclear nonproliferation, Kenya`s views on the NPT, Prospects for establishing a zone free of weapons of mass destruction in the middle east, effects of a special nuclear weapon materials cut-off convention, and The UK view of NPT renewal.

  14. Proliferation Persuasion. Coercive Bargaining with Nuclear Technology

    Energy Technology Data Exchange (ETDEWEB)

    Volpe, Tristan A. [George Washington Univ., Washington, DC (United States)

    2015-08-31

    Why do states wait for prolonged periods of time with the technical capacity to produce nuclear weapons? Only a handful of countries have ever acquired the sensitive nuclear fuel cycle technology needed to produce fissile material for nuclear weapons. Yet the enduring trend over the last five decades is for these states to delay or forgo exercising the nuclear weapons option provided by uranium enrichment or plutonium reprocessing capabilities. I show that states pause at this threshold stage because they use nuclear technology to bargain for concessions from both allies and adversaries. But when does nuclear latency offer bargaining benefits? My central argument is that challengers must surmount a dilemma to make coercive diplomacy work: the more they threaten to proliferate, the harder it becomes to reassure others that compliance will be rewarded with nuclear restraint. I identify a range of mechanisms able to solve this credibility problem, from arms control over breakout capacity to third party mediation and confidence building measures. Since each step towards the bomb raises the costs of implementing these policies, a state hits a sweet spot when it first acquires enrichment and/or reprocessing (ENR) technology. Subsequent increases in proliferation capability generate diminishing returns at the bargaining table for two reasons: the state must go to greater lengths to make a credible nonproliferation promise, and nuclear programs exhibit considerable path dependency as they mature over time. Contrary to the conventional wisdom about power in world politics, less nuclear latency thereby yields more coercive threat advantages. I marshal new primary source evidence from archives and interviews to identify episodes in the historical record when states made clear decisions to use ENR technology as a bargaining chip, and employ this theory of proliferation persuasion to explain how Japan, North Korea, and Iran succeeded and failed to barter concessions from the

  15. Anticoagulant Resistance

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte

    to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...... agent in the sewers. Low level of resistance was found in locations regardless of management strategy. Mutations in the VKORC1 gene have been proposed to confer anticoagulant resistance and an Y139C VKORC1 mutation has been identified in Danish resistant rats. All animals were tested with an Y139C...... specific PCR to verify this genetic form of resistance, but in contrast to animals tested from various surface populations, we could not confirm the Y139C mutation in any of the sewer rats. Our findings could indicate that resistance in surface and sewer population may be caused by different mechanism...

  16. Camptothecin resistance

    DEFF Research Database (Denmark)

    Brangi, M; Litman, Thomas; Ciotti, M

    1999-01-01

    The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells...... and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines...... demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment...

  17. Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

    Science.gov (United States)

    Wijethilake, Chaminda

    2017-07-01

    This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Towards sustainable development

    Science.gov (United States)

    Munn, R. E.

    Sustainable development is a difficult phrase to define, particularly in the context of human ecosystems. Questions have to be asked, such as "Sustainable for whom?" "Sustainable for what purposes?" "Sustainable at the subsistence or at the luxury level?" and "Sustainable under what conditions?" In this paper, development is taken to mean improving the quality of life. (If development were to mean growth, then it could not be sustained over the long term.) Studies of development must, of course, consider economic factors, particularly in the case of societies who suffer from the pollution of poverty. However, cultural and environmental factors are equally important. In fact, development is not sustainable over the long term if it is not ecologically sustainable. The terms maximum sustainable yield of a renewable resource, carrying capacity of a region and assimilative capacity of a watershed or airshed are discussed. Approaches using these resource management tools are recommended when external conditions are not changing very much. The problem today is that unprecedented rates of change are expected in the next century, not only of environmental conditions such as climate but also of socioeconomic conditions such as renewable resource consumption and populations (of both people and of automobiles)! In rapidly changing situations, policies must be adopted that strengthen resilence and ecosystem integrity; that is, society must increase its ability to adapt. Maintaining the status quo is a long-term prescription for disaster. The problem is of course that little is known about how to design strategies that will increase resilience and ecosystem integrity, and this area of research needs to be strengthened. Some suggestions on appropriate indicators of ecosystem integrity are given in the paper but these need considerable refinement. One of the main problems with long-term environmental policy formulation is the uncertainty to be expected, including the possibility

  19. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  20. Sustainable Consumption Dilemmas

    Directory of Open Access Journals (Sweden)

    Kees Vringer

    2017-06-01

    Full Text Available To examine which considerations play a role when individuals make decisions to purchase sustainable product varieties or not, we have conducted a large scale field experiment with more than 600 participating households. Households can vote on whether the budgets they receive should only be spent on purchasing the sustainable product variety, or whether every household in a group is free to spend their budget on any product variety. By conducting several treatments, we tested whether people tend to view sustainable consumption as a social dilemma or as a moral dilemma. We find little support for the hypothesis that social dilemma considerations are the key drivers of sustainable consumption behaviour. Participants seem to be caught in a moral dilemma in which they not only weigh their individual financial costs with the sustainable benefits but they also consider the consequences of restricting other people’s freedom of choice. Complementary survey results further substantiate this claim and show that many people are reluctant to impose restrictions on their peers, but, at the same time, our results also suggest substantial support for the government to regulate the availability of unsustainable product varieties.

  1. Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.

    Science.gov (United States)

    Mukherjee, Abir; Ma, Yibao; Yuan, Fang; Gong, Yongling; Fang, Zhenyu; Mohamed, Esraa M; Berrios, Erika; Shao, Huanjie; Fang, Xianjun

    2015-09-01

    Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF) elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1) and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Nilotinib impairs skeletal myogenesis by increasing myoblast proliferation

    Directory of Open Access Journals (Sweden)

    Osvaldo Contreras

    2018-02-01

    Full Text Available Abstract Background Tyrosine kinase inhibitors (TKIs are effective therapies with demonstrated antineoplastic activity. Nilotinib is a second-generation FDA-approved TKI designed to overcome Imatinib resistance and intolerance in patients with chronic myelogenous leukemia (CML. Interestingly, TKIs have also been shown to be an efficient treatment for several non-malignant disorders such fibrotic diseases, including those affecting skeletal muscles. Methods We investigated the role of Nilotinib on skeletal myogenesis using the well-established C2C12 myoblast cell line. We evaluated the impact of Nilotinib during the time course of skeletal myogenesis. We compared the effect of Nilotinib with the well-known p38 MAPK inhibitor SB203580. MEK1/2 UO126 and PI3K/AKT LY294002 inhibitors were used to identify the signaling pathways involved in Nilotinib-related effects on myoblast. Adult primary myoblasts were also used to corroborate the inhibition of myoblasts fusion and myotube-nuclei positioning by Nilotinib. Results We found that Nilotinib inhibited myogenic differentiation, reducing the number of myogenin-positive myoblasts and decreasing myogenin and MyoD expression. Furthermore, Nilotinib-mediated anti-myogenic effects impair myotube formation, myosin heavy chain expression, and compromise myotube-nuclei positioning. In addition, we found that p38 MAPK is a new off-target protein of Nilotinib, which causes inhibition of p38 phosphorylation in a similar manner as the well-characterized p38 inhibitor SB203580. Nilotinib induces the activation of ERK1/2 and AKT on myoblasts but not in myotubes. We also found that Nilotinib stimulates myoblast proliferation, a process dependent on ERK1/2 and AKT activation. Conclusions Our findings suggest that Nilotinib may have important negative effects on muscle homeostasis, inhibiting myogenic differentiation but stimulating myoblasts proliferation. Additionally, we found that Nilotinib stimulates the activation

  3. Measuring soil sustainability via soil resilience.

    Science.gov (United States)

    Ludwig, Marie; Wilmes, Paul; Schrader, Stefan

    2017-10-17

    Soils are the nexus of water, energy and food, which illustrates the need for a holistic approach in sustainable soil management. The present study therefore aimed at identifying a bioindicator for the evaluation of soil management sustainability in a cross-disciplinary approach between soil science and multi-omics research. For this purpose we first discuss the remaining problems and challenges of evaluating sustainability and consequently suggest one measurable bioindicator for soil management sustainability. In this concept, we define soil sustainability as the maintenance of soil functional integrity. The potential to recover functional and structural integrity after a disturbance is generally defined as resilience. This potential is a product of the past and the present soil management, and at the same time prospect of possible soil responses to future disturbances. Additionally, it is correlated with the multiple soil functions and hence reflecting the multifunctionality of the soil system. Consequently, resilience can serve as a bioindicator for soil sustainability. The measurable part of soil resilience is the response diversity, calculated from the systematic contrasting of multi-omic markers for genetic potential and functional activity, and referred to as potential Maximum Ecological Performance (MEPpot) in this study. Calculating MEPpot will allow to determine the thresholds of resistance and resilience and potential tipping points for a regime shift towards irreversible or permanent unfavorable soil states for each individual soil considered. The calculation of such ecosystem thresholds is to our opinion the current global cross-disciplinary challenge. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained.

    Science.gov (United States)

    Nokia, Miriam S; Lensu, Sanna; Ahtiainen, Juha P; Johansson, Petra P; Koch, Lauren G; Britton, Steven L; Kainulainen, Heikki

    2016-04-01

    Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents. Little is known about the effects of high-intensity interval training (HIT) or of purely anaerobic resistance training on AHN. Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats. We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity. Our results confirm that sustained aerobic exercise is key in improving AHN. Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high-intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low-response trainer (LRT) and high-response trainer (HRT) adult male rats to various forms of physical exercise for 6-8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin-positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non-significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on

  5. Sustainable food systems for optimal planetary health.

    Science.gov (United States)

    Canavan, Chelsey R; Noor, Ramadhani A; Golden, Christopher D; Juma, Calestous; Fawzi, Wafaie

    2017-06-01

    Sustainable food systems are an important component of a planetary health strategy to reduce the threat of infectious disease, minimize environmental footprint and promote nutrition. Human population trends and dietary transition have led to growing demand for food and increasing production and consumption of meat, amid declining availability of arable land and water. The intensification of livestock production has serious environmental and infectious disease impacts. Land clearing for agriculture alters ecosystems, increases human-wildlife interactions and leads to disease proliferation. Context-specific interventions should be evaluated towards optimizing nutrition resilience, minimizing environmental footprint and reducing animal and human disease risk. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  6. Sustainability and sacred values

    Directory of Open Access Journals (Sweden)

    John Cairns Jr.

    2002-09-01

    Full Text Available Successful implementation of the quest for sustainable use of the planet requires that human society both reexamine and expand present views of what is sacred and what is not. The most important aspect will be going beyond a homocentric focus to a biocentric emphasis. A unifying theme would be the desire to leave a habitable planet for human descendants and those of other species. It is unlikely that society can be confident of achieving sustainability until persuasive evidence supporting this belief has existed for several generations. In order for sustainable use of the planet to persist indefinitely, the conditions essential to this state must be morally preserved on sacred grounds. Viewing natural systems as sacred requires not only preventing damage to them but, wherever possible, repairing damage to them caused by humankind.

  7. Sustainability & Organization Design

    DEFF Research Database (Denmark)

    Rasmussen, Morten Bygvraa; Obel, Børge; Kallehave, Pernille

    of global governance to match the new dynamics and consequences of globalization. Governments are re-examining corporate accountability to society and how companies earn their license to operate. Furthermore companies are re-examining their code of conduct and leadership values. Thus, sustainability...... is an important driver in organizations and its impact and effect on organization design is critical. Development of organization design, structure, processes, and human skills and values are needed to create the sustainable organization for the future. This paper discusses the requirements to be a sustainable...... organization. Here we follow the Global Compact criteria. The consequences for processes, structure, and human skills and values are analyzed. In particular the analysis will investigate exploration and exploitation from a holistic perspective using the principles of requisite variety and information...

  8. QUEST for sustainable CPD

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund

    2014-01-01

    in the local learning communities we have seen a positive trend from the first to the last course-module, but with great variation between schools. Factors potentially supporting sustainable development seem to be about (1) continuingly scaffolding teachers’ collaborative inquiries by organizing activities......Continuous Professional Development (CPD) can be crucial for reforming science teaching, but more knowledge is needed about how to support sustainability of the effects. The Danish QUEST project is a large scale, long-term collaborative CPD project designed according to widely agreed criteria...... phase. The findings are discussed looking forward to the institutionalization phase identifying factors potentially supporting sustainable development pertaining to local science teachers developing a shared focus on student learning in science, and perceived individual and collective efficacy...

  9. Sustainable urban development

    DEFF Research Database (Denmark)

    Jensen, Jesper Ole; Christensen, Toke Haunstrup; Gram-Hanssen, Kirsten

    Sustainability in urban planning has a long history and it has been a widespread solution to build high and compact in order to minimise the need for transportation, land use and heating. Recent research, however, points towards the need for a supplementary approach which includes the consumer...... behaviour of the household. This approach necessarily has to work from below and include the citizens, as it is their daily practices that have to be challenged. This article reviews the literature of to what extent compact cities are the most sustainable and it use lifestyle interpretations of urbane forms...... to challenge the compact cities approach. As an alternative or supplementary approach the article introduce practice theory as a way to understand consumption and it gives examples on how this approach can be used to inspire local authorities to alternative and supplementary strategies of achieving sustainable...

  10. Sustainable Consumption: Research Challenges

    DEFF Research Database (Denmark)

    Reisch, Lucia A.; Cohen, Maurie J.; Thøgersen, John

    The Board of the Swedish Foundation for Strategic Environmental Research (Mistra) decided in October 2015 that a proposal for a funding application call in the research area of “sustainable consumption” should be drawn up. According to the statutes of Mistra, research funded by the foundation...... for achieving industrial applications shall be taken advantage of.” The funding application call to be developed by Mistra is to be based on an analysis of the current state of the art of research and of society’s knowledge needs regarding sustainable consumption. Mistra commissioned a committee of four...... the orientation of a new research program to be used as draft text for the call for funding applications. The aim of this background report is hence to shed light on future research topics within sustainable consumption from a Swedish perspective. The research pro- moted should help to develop Sweden...

  11. Sustainable Supply Chain Design

    DEFF Research Database (Denmark)

    Bals, Lydia; Tate, Wendy

    A significant conceptual and practical challenge is how to integrate triple bottom line (TBL; including economic, social and environmental) sustainability into global supply chains. Although this integration is necessary to slow down global resource depletion, understanding is limited of how...... to implement TBL goals across the supply chain. In supply chain design, the classic economic perspective still dominates, although the idea of the TBL is more widely disseminated. The purpose of this research is to add to the sustainable supply chain management literature (SSCM) research agenda...... by incorporating the physical chain, and the (information and financial) support chains into supply chain design. This manuscript tackles issues of what the chains are designed for and how they are designed structurally. Four sustainable businesses are used as illustrative case examples of innovative supply chain...

  12. Sustainability in a nutshell.

    Science.gov (United States)

    Silvertown, Jonathan

    2004-06-01

    Sustainable exploitation is widely advocated as a strategy for reconciling economic pressures upon natural habitats with nature conservation. Two recent papers examine different aspects of the sustainability of the nut harvest on wild populations of Brazil nut trees Bertholletia excelsa in Amazonia. Peres et al. find that many populations of the Brazil nut tree lack juvenile trees and are not regenerating. In a socioeconomic study, Escobal and Aldana find that nut-gathering provides insufficient income on its own to support nut-gatherers and that their other income-raising activities damage the forest. The existence of a market for rainforest products is, therefore, not sufficient on its own to prevent habitat destruction or the overexploitation of the resource and a more sophisticated approach to sustainability is required. Development of a market in ethically traded Brazil nuts might be one solution.

  13. TOURISM AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Gina Ionela Butnaru

    2014-06-01

    Full Text Available Tourism and sustainable development are the subject of many initiatives and public or private debates in Romania. The main problem to which these initiatives try to find an answer is mostly related to the income generation for the local communities by using rationally and efficiently the local potential, in agreement with the economic, social, natural, and cultural factors. Consequently, some measures should be taken, and the tourist sector as a whole needs all the methods of sustainable development: new technologies, change of social behaviour, change of environmental legislation, methods of environmental management, better planning and development of control procedures. In this article, we presented a model of tourism development which should be applied in all the regions of great tourist attraction, and we realised a synthesis of the socio-economic advantages of sustainable tourism.

  14. Is Globalisation Sustainable?

    Directory of Open Access Journals (Sweden)

    Mohsin Raza

    2010-01-01

    Full Text Available It is clear that globalisation is something more than a purely economic phenomenon manifesting itself on a global scale. Among the visible manifestations of globalisation are the greater international movement of goods and services, financial capital, information and people. In addition, there are technological developments, more international cultural exchanges, facilitated by the freer trade of more differentiated products as well as by tourism and immigration, changes in the political landscape and ecological consequences. In this paper, we link the Maastricht Globalisation Index with Sustainability Indices to analyse if more globalised countries are doing better in terms of sustainable development and its dimensions. The results seem to suggest that the process of globalisation may render world development more sustainable.

  15. Environment and sustainability

    DEFF Research Database (Denmark)

    Paavola, Jouni; Røpke, Inge

    2015-01-01

    This chapter reviews socio-economic research on the environment and sustainability. The chapter first explores core aspects of socio-economics, examines how socio-economics has related to the agenda of research on the environment, and assesses how socio-economic research on the environment became...... to a research agenda for ‘socio-ecological economics’. Sustainable consumption and global environmental change are already important areas of research for it. But ecological macroeconomics is also needed to formulate coordinated responses to multiple crises such as economic downturn, climate change and loss...

  16. Developing Ecological Sustainability

    DEFF Research Database (Denmark)

    Hedman, Jonas; Henningsson, Stefan

    2016-01-01

    IS initiatives become part of a firm’s overall strategy and part of the organizational sustainability process. We find that Green IS initiatives are initiated through a bottom-up process where environmentally concerned individuals identify issues and become Green IS champions. They use their authority...... and edification skills to promote Green IS to the organizational agenda. If the issue is aligned with the organizational agenda, it receives management’s endorsement. The empirical case also shows two types of systemic feedback that can fuel a self-reinforcing sustainability process. The first type of feedback...

  17. Sustainability Base Construction Update

    Science.gov (United States)

    Mewhinney, Michael

    2012-01-01

    Construction of the new Sustainability Base Collaborative support facility, expected to become the highest performing building in the federal government continues at NASA's Ames Research Center, Moffet Field, Calif. The new building is designed to achieve a platinum rating under the leadership in Energy and Environment Design (LEED) new construction standards for environmentally sustainable construction developed by the U. S. Green Building Council, Washington, D. C. When completed by the end of 2011, the $20.6 million building will feature near zero net energy consumption, use 90 percent less potable water than conventionally build buildings of equivalent size, and will result in reduced building maintenance costs.

  18. Towards sustainable food production

    DEFF Research Database (Denmark)

    Aramyan, Lusine H; Hoste, Robert; van den Broek, Willie

    2011-01-01

    allocation of pork supply chain activities in Europe. Supply chain production and distribution activities are optimized in various scenarios based on economic and sustainability performance indicators. A mixed integer linear programming (MILP) model, which includes piglet production, fattening, slaughtering......, as minimizing costs will not always lead to an optimal reduction in CO2 equivalent emissions, a differentiated strategy is needed for the European pork sector to move towards more sustainable production......European pork supply chains, like other agri-food supply chains, currently face numerous challenges such as globalization, emerging markets, changing consumer requirements, and new governmental regulations related to issues such as environmental pollution and food safety. These challenges require...

  19. SUSTAINABLE DEVELOPMENT PARADIGM - SYNOPSIS

    Directory of Open Access Journals (Sweden)

    Constantinescu Andreea

    2014-07-01

    Full Text Available Even if sustainable development is a concept that gained quite recently its scientific prestige, through contribution of researchers its content has upgraded to a high degree of conceptual luggage and, through contribution from governance representatives, has gained an impressive good-practice background. Allowing the use of different methodological premises and conceptual tools, sustainable development paradigm is equipped with all the elements that would allow the opening of new horizons of knowledge. Based on the facility which can operate the concept of sustainable development, the European Union aims to develop both a more competitive economy based on environmental protection as well as a new governance of economic policy. This on one hand demonstrates the sustainable development ability to irradiate creativity towards the establishment of interdisciplinary bridges and on the other hand explains the growing interest of researchers interested in the problem of analyzing in detail this fruitful concept. Launched first as a theoretical framework to serve justify actions responsible for weighting economic growth, the concept of Sustainable Development has quickly become a topic of ethical debate circumscribed to the area of perfectibility of human nature to the necessity registry. In this regard, the philosophical content of this paradigm could not remain outside researchers concerns, who want to provide both policy makers and the general public a wide range of evidence to demonstrate the viability of this paradigm. Academia waits until maximization of the contribution of governance to achieve sustainable economic development, which consists in conjunction of this upward path with the momentum given by public policy sync, perfectly adapted for globalization era and all crises to come. However, because this concept based its structure and composition on three pillars, equally important economy, society and environment any attempt to strengthen

  20. Sustainable Buildings in Interaction

    DEFF Research Database (Denmark)

    Elle, Morten

    2007-01-01

    The first attempts to build sustainable buildings in Denmark were typically located on the countryside. The basic idea was to create buildings that were independent of the technical infrastructure. District heating has, however, been the dominating solution to heating in buildings in Denmark......, and the focus on sustainable building have gradually turned from special houses on the countryside to normally looking houses in the urban fabric, integrated in the technical infrastructure. Some new built urban areas in Denmark will, however, not have to be supplied with district heating – these developments...