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Sample records for leukemic lgls bid

  1. Bid specifications and bid evaluations

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1977-01-01

    Bid specifications are in view of the size of these projects important and comprehensive documents. The basic content and set up of the specifications are discussed such as: 1) Bid invitation letter, 2) instruction to bidders, 3) draft contract (terms and conditions), 4) technical specifications, 5) side data and information. - The evaluations of bids for nuclear power stations is due to the complexity of such bids a difficult undertaking. Evaluation methods and approaches which can be applied for such bid evaluations are discussed as well as the preparations which are required for carrying out such evaluations. (orig.) [de

  2. Leukemic optic neuropathy.

    Science.gov (United States)

    Brown, G C; Shields, J A; Augsburger, J J; Serota, F T; Koch, P

    1981-03-01

    The clinical course and ophthalmic manifestations of an eight year old child with acute undifferentiated leukemia and unilateral blindness secondary to leukemic optic nerve head infiltration are described. At autopsy the involved nerve head and peripapillary retina demonstrated massive leukemic cell infiltration and hemorrhagic necrosis. This manifestation of leukemia is quite uncommon and prognosis for life in such cases is poor with existing methods of therapy.

  3. Normal and Leukemic Hematopoiesis

    NARCIS (Netherlands)

    Vercauteren, Suzanne Maria

    2003-01-01

    Acute Myeloid Leukemia (AML) is a clonal myeloproliferative disease characterized by an uncontrolled proliferation and block in differentiation of myeloid committed blood cells in the bone marrow. Despite the lack of mature cells derived from the leukemic clone in the majority of AML patients, AML

  4. 23 CFR 635.113 - Bid opening and bid tabulations.

    Science.gov (United States)

    2010-04-01

    ... CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.113 Bid opening and bid tabulations. (a) All bids... contractors, during the period following the opening of bids and before the award of the contract shall not be...

  5. Economic bid evaluation

    International Nuclear Information System (INIS)

    Bode, T.

    1975-01-01

    When it is intended to install a new nuclear power station, the usual procedure is to invite for tenders. In due course, bids will be received from various manufacturers, out of which the most favourable one is then to be selected. Appraisal is concluded in the Economic Bid Evaluation, the purpose of which is to define the economically most favourable bid by comparing overall costs and benefits of the various alternatives. Thus, Economic Bid Evaluation is a most important instrument for deciding on award of contract. (orig.) [de

  6. The BID`s of New York

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    , the aim is to present a theoretical and analytical framework for understanding such ? urban mini territories? both in relation to urban power an politics, and in relation to the spatial layout of such forms of urban intervention. In section two the paper shortly describe the phenomenon of New York BIDs....... In the third part of the paper empirical field data from selected New York BIDs are presented. Finally the paper ends with a section in which concluding remarks will be accompanied by reflections on the comparative similarities and differences to European cities....

  7. Leukemic cell labeling with indium-111-oxine

    International Nuclear Information System (INIS)

    Uchida, T.; Takagi, Y.; Matsuda, S.; Yui, T.; Ishibashi, T.; Kimura, H.; Kariyone, S.

    1984-01-01

    Leukemic cells were labeled with In-111-oxine in patients with acute leukemia. In vitro labeling studies revealed that labeling efficiency reached maximum 80.8 +- 3.6% (mean +- 1SD) by 2 times washes after 20 minutes incubation time. Cell viability was assessed by trypan blue exclusion test and in vitro culture of leukemic cells, which showed no cellular damage during labeling procedure. Elution of In-111 from the labeled cells was 10.0 +- 1.2% at 12 hours after labeling. For in vivo leukemic cell kinetic studies, more than 10/sup 8/ leukemic cells separated from Ficoll-Hypacque sedimentation were labeled by 30 minutes of In-111-oxine incubation and two times washes at 37 0 C. In vivo studies were performed in 7 patients with acute myeloblastic, lymphoblastic leukemia and blastic crisis of chronic myelocytic leukemia. Labeled leukemic cells disappeared in single exponential fashion with half life of 9.6 to 31.8 hours. Total leukemic cell pool in peripheral circulation was calculated, which correlated well with peripheral leukemic cell counts (r=0.99). No relationship was observed between total leukemic cell pool and leukemic cell turnover rate. Migration patterns of labeled leukemic cells showed that pulmonary uptake was evident within 15 minutes after the infusion and returned to base-line. Splenic and hepatic uptake showed gradual increase up to 24 hours. Bone marrow accumulation was shown only in 2 cases. Presently, there are no suitable radionuclides for leukemic cell labeling. In-111-oxine labeled leukemic cells would overcome this difficulty

  8. How does the revelation of previous bid affect new bid?

    OpenAIRE

    Li, Yingzi; Gallardo, R. Karina; McCracken, Vicki A.; Yue, Chengyan; Luby, James; McFerson, James R.

    2014-01-01

    This study investigates the effect of the revelation of posted bids in second-price experimental auctions for apple quality attributes under the experimental design where information is added progressively across rounds. We find that the revelation of posted bids does not bias the following bids and that increased information about the apple increases the accuracy of participants’ following bids. Therefore, the final round bids are used to evaluate consumers’ willingness to pay for the apple ...

  9. DMEPOS Competitive Bidding

    Data.gov (United States)

    U.S. Department of Health & Human Services — The DMEPOS Competitive Bidding Program was mandated by Congress through the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The statute...

  10. Who wins olympic bids?

    OpenAIRE

    Maennig, Wolfgang; Vierhaus, Christopher

    2014-01-01

    The prospect of hosting the Olympic Games is attractive to many cities around the world. This article examines 147 variables’ potential to discriminate successful from unsuccessful Olympic bids. Our stepwise, rank-ordered logistic regression model includes 10 determinants supporting the contention that economic, political and sports/Olympic factors are important for winning the host city election. IOC members favor cities if more than 2/3 of the population support the bid, but disfavor biddin...

  11. Bid Responsiveness and the Acceptable Nonconforming Bid.

    Science.gov (United States)

    1979-09-30

    the. fuidaIenta prin ciples of responsiveness. The Conhl trot ler, hnwever, has ta ken this sairn "reasonable- tit’, ’ t. ,t ’’ , T (I I e l iLd i I...cvo rcome otherwise material deviation i f; the bid, thereby renderin gj it a(,ceptable. Tne Comptroller General’s o) p loach to the , i..sue ft

  12. Technical bid evaluation

    International Nuclear Information System (INIS)

    Bruchhausen, E. v.

    1975-01-01

    It is shown which kind of problems arise for the owners of the project and what is the recommendable method of approach. A detailed description of the necessary working team, information in delegation of work and tasks of procedure, criteria of valuation and classification method. Examples of schemes are shown which are the basis of the technical bid evaluation: tables 'data of system/component' and 'scope of supply'. The procedure of normalization of the bids and of specifying the owners supplies are explained. The content of the final report is described. (HP) [de

  13. Essays on bid rigging

    NARCIS (Netherlands)

    Seres, Gyula

    2016-01-01

    Manipulating prices in auctions raises antitrust concerns. Collusion lowers the revenue of the auctioneer and creates information rents. Bid rigging is a prevalent phenomenon and the affected market is enormous. Public procurement amounts to between 10 and 25 percent of national GDP in

  14. Optimal GENCO bidding strategy

    Science.gov (United States)

    Gao, Feng

    Electricity industries worldwide are undergoing a period of profound upheaval. The conventional vertically integrated mechanism is being replaced by a competitive market environment. Generation companies have incentives to apply novel technologies to lower production costs, for example: Combined Cycle units. Economic dispatch with Combined Cycle units becomes a non-convex optimization problem, which is difficult if not impossible to solve by conventional methods. Several techniques are proposed here: Mixed Integer Linear Programming, a hybrid method, as well as Evolutionary Algorithms. Evolutionary Algorithms share a common mechanism, stochastic searching per generation. The stochastic property makes evolutionary algorithms robust and adaptive enough to solve a non-convex optimization problem. This research implements GA, EP, and PS algorithms for economic dispatch with Combined Cycle units, and makes a comparison with classical Mixed Integer Linear Programming. The electricity market equilibrium model not only helps Independent System Operator/Regulator analyze market performance and market power, but also provides Market Participants the ability to build optimal bidding strategies based on Microeconomics analysis. Supply Function Equilibrium (SFE) is attractive compared to traditional models. This research identifies a proper SFE model, which can be applied to a multiple period situation. The equilibrium condition using discrete time optimal control is then developed for fuel resource constraints. Finally, the research discusses the issues of multiple equilibria and mixed strategies, which are caused by the transmission network. Additionally, an advantage of the proposed model for merchant transmission planning is discussed. A market simulator is a valuable training and evaluation tool to assist sellers, buyers, and regulators to understand market performance and make better decisions. A traditional optimization model may not be enough to consider the distributed

  15. Bidding strategy in pay-as-bid power markets

    International Nuclear Information System (INIS)

    Oloomi-Buygi, M.; Nazarian, H.

    2007-01-01

    Electricity markets around the world can be classified as pool-based electricity markets; pure bilateral contract markets; and hybrid markets. The bidding strategy has emerged as an important issue for producers in pool-based electricity markets. Power producers can use several approaches to develop bidding strategies that determine the optimal bid to maximize profit. The various approaches fall into 2 categories, notably forecasting market clearing prices, and estimating the behaviour of other competitors. This paper presented a simple and efficient approach for developing a bidding strategy in pay-as-bid electricity markets. It used the multiple step bid to estimate the optimal bid. One step was allocated to revenue earning while the other steps were allocated to information acquiring. Information acquiring steps obtain information from the market for estimating the optimal bid of the next day. The proposed method was used at a specified power generating unit operating in the Iranian electricity market. The study showed that the proposed bidding strategy can increase the total revenue of the unit by thirty nine per cent. 22 refs., 8 figs

  16. Contract Bidding for Rehabilitation Facilities.

    Science.gov (United States)

    Gilbertson, Alan D.

    This book for sheltered workshop administrators outlines and explains the essential elements of an accurate work bid. Part 1 discusses issues that need to be resolved prior to calculating costs for a potential job. Part 2 describes the factors necessary for determining accurate bids, including direct costs (job setup, direct labor, direct…

  17. Bid invitations for nuclear power stations

    International Nuclear Information System (INIS)

    Zijl, N.A. van.

    1975-01-01

    Types of bid invitations, basic requirements on bid invitation documents, basic content of a turnkey bid invitation (bid invitation letter, instructions to the bidders, terms and conditions of the draft contract, technical specifications, site data and information), nuclear fuel procurement, differences turnkey - non-turnkey, legal, commerical, and technical matters concerning the contract document. (HP) [de

  18. 24 CFR 291.304 - Bidding process.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Bidding process. 291.304 Section 291.304 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Family Mortgage Loans § 291.304 Bidding process. (a) Submission of bids. All bids must be submitted to...

  19. Leukemic Oral Manifestations and their Management.

    Science.gov (United States)

    Francisconi, Carolina Favaro; Caldas, Rogerio Jardim; Oliveira Martins, Lazara Joyce; Fischer Rubira, Cassia Maria; da Silva Santos, Paulo Sergio

    2016-01-01

    Leukemia is the most common neoplastic disease of the white blood cells which is important as a pediatric malignancy. Oral manifestations occur frequently in leukemic patients and may present as initial evidence of the disease or its relapse. The symptoms include gingival enlargement and bleeding, oral ulceration, petechia, mucosal pallor, noma, trismus and oral infections. Oral lesions arise in both acute and chronic forms of all types of leukemia. These oral manifestations either may be the result of direct infiltration of leukemic cells (primary) or secondary to underlying thrombocytopenia, neutropenia, or impaired granulocyte function. Despite the fact that leukemia has long been known to be associated with oral lesions, the available literature on this topic consists mostly of case reports, without data summarizing the main oral changes for each type of leukemia. Therefore, the present review aimed at describing oral manifestations of all leukemia types and their dental management. This might be useful in early diagnosis, improving patient outcomes.

  20. The Netherlands Bid Bood (GBIF)

    NARCIS (Netherlands)

    Los, W.

    2001-01-01

    GBIF=Global Biodiversity Information Facility. The Bid Book was prepared for the Ministry of Education, Culture and Sciences, the Netherlands by a working group, co-ordinated by the University of Amsterdam.

  1. Leukemic meningitis involving the cauda equina: a case report

    International Nuclear Information System (INIS)

    Lee, Dong Hyun; Kim, Ho Kyun; Lee, Young Hwan

    2008-01-01

    The CNS involvement by leukemia may either be meningeal or parenchymal, although meningeal infiltration of leukemic cells, known as leukemic meningitis is more common. We report a case of leukemic meningitis involving the cauda equina in a patient with an acute lymphoblastic crisis which transformed from the chronic phase of chronic myeloid leukemia. An MR image revealed diffuse enlargement and peripheral ring enhancement of the nerve roots of the cauda equina

  2. Leukemic meningitis involving the cauda equina: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Hyun; Kim, Ho Kyun; Lee, Young Hwan [School of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)

    2008-07-15

    The CNS involvement by leukemia may either be meningeal or parenchymal, although meningeal infiltration of leukemic cells, known as leukemic meningitis is more common. We report a case of leukemic meningitis involving the cauda equina in a patient with an acute lymphoblastic crisis which transformed from the chronic phase of chronic myeloid leukemia. An MR image revealed diffuse enlargement and peripheral ring enhancement of the nerve roots of the cauda equina.

  3. tBid and cardiolipin

    DEFF Research Database (Denmark)

    Klösgen, Beate; Perry, Mark; Rostovtseva, Tanya

    2007-01-01

    The abundant presence of cardiolipin (CL) in mitochondria membranes has given rise to the suspicion that this lipid play be an essential role in triggering cell apoptosis, possibly by mechanically destabilizing the host membrane and thus enhancing the effect of the tBid apoptosis protein. Therefore...... and absence of CL. We interpret this as a formation of patches of protein-lipid clusters that in effect reduce the amount of expandable fluid membrane area. The rupture tension falls significantly as soon as tBid is present on the outer vesicle membrane....

  4. Emerging behavior in electronic bidding

    Science.gov (United States)

    Yang, I.; Jeong, H.; Kahng, B.; Barabási, A.-L.

    2003-07-01

    We characterize the statistical properties of a large number of agents on two major online auction sites. The measurements indicate that the total number of bids placed in a single category and the number of distinct auctions frequented by a given agent follow power-law distributions, implying that a few agents are responsible for a significant fraction of the total bidding activity on the online market. We find that these agents exert an unproportional influence on the final price of the auctioned items. This domination of online auctions by an unusually active minority may be a generic feature of all online mercantile processes.

  5. Takeover bids and insider trading

    NARCIS (Netherlands)

    Nelemans, Matthijs; Bainbridge, Stephen M.

    2014-01-01

    This paper analyses the law and economics of insider trading in the context of takeover bids, focusing on the European regulatory framework. We distinguish between trading by the bidder, by the target and by classical insiders and first address the issue of precisely when information about potential

  6. 36 CFR 223.51 - Bid monitoring.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bid monitoring. 223.51 Section 223.51 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND... Bid monitoring. Each Regional Forester shall monitor bidding patterns on timber sales to determine if...

  7. 42 CFR 414.910 - Bidding process.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Bidding process. 414.910 Section 414.910 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Under Part B § 414.910 Bidding process. (a) Entities may bid to furnish CAP drugs in all competitive...

  8. 36 CFR 223.231 - Bidding methods.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.231... methods. The Contracting Officer or designated forest officer shall offer advertised sales of special forest products through sealed bid or sealed bid followed by oral auction. The method selected shall: (a...

  9. 30 CFR 256.44 - Bids disqualified.

    Science.gov (United States)

    2010-07-01

    ... by law, regulation, lease or stipulation to lease shall not disqualify an otherwise qualified bid; or... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Bids disqualified. 256.44 Section 256.44... OIL AND GAS IN THE OUTER CONTINENTAL SHELF Issuance of Leases § 256.44 Bids disqualified. The...

  10. 10 CFR 452.5 - Bidding procedures.

    Science.gov (United States)

    2010-01-01

    ... for the reverse auction. (e) Bid evaluation and incentive awards selection procedures include the... bids, preference will be given to the lowest tied bidder based on DOE's evaluation of the extent to... feedstock suppliers. (4) In the event more than one lowest tied bid equally meets the standards in paragraph...

  11. Nature of leukemic stem cells in murine myelogenous leukemia

    International Nuclear Information System (INIS)

    Yoshida, K.; Nemoto, K.; Nishimura, M.; Hayata, I.; Inoue, T.; Seki, M.

    1986-01-01

    We investigated the nature of myelogenous leukemic stem cells in mice. L-8057, a megakaryoblastic leukemia cell line used in this study, produces in vivo and in vitro colonies. By means of typical chromosomal aberrations in L-8057, one can conveniently detect the origin of the cells in each colony derived from a leukemic stem cell. Direct evidence of whether cells from each colony had leukemogenicity in recipient mice was successfully obtained by the colony transplantation assay. Both leukemic colony-forming unit-spleen (L-CFU-s) and leukemic colony-forming unit-culture (L-CFU-c) in L-8057 may have belonged to the same differentiating stage in the stem cells because of their similar radiosensitivity, although some parts of the L-CFU of L-8057 seemed to have lost their capability to regenerate L-CFU-s when the cells were plated in dishes. This leukemic stem cell preserves high self-renewal ability in vitro after 10 passages. In addition, in vitro colony formation by this leukemic cell during the above course of serial passages did not require any additional exogenous stimulators. The same sort of trials have been made on other types of leukemias. Leukemic stem cells showed remarkable variety in their response to stimulating factors and in their self-renewal activity, which suggests that they may have consisted of heterogeneous populations

  12. The impacts of different bidding segment numbers on bidding strategies of generation companies

    International Nuclear Information System (INIS)

    Wang, L.; Yu, C.W.; Wen, F.S.

    2008-01-01

    In a competitive electricity market, generation companies design bidding strategies to maximize their individual profits subject to the constraints imposed by bidding rules. For a generation company, obviously, the optimal bidding strategy and hence the potential of exercising market power may be different if different bidding rules are employed. Hence, a well-designed bidding protocol is vital to the effective and efficient operation of an electricity market. Based on the widely used stepwise bidding rules, the impacts of different numbers of bidding segments on the bidding strategies of generation companies are investigated. This study is focused on a price-taker generation company in an electricity market. A probabilisic model is used to simulate electricity price in the competitive market environment. With a given number of bidding segments, the optimal bidding strategy for a price-taker generation company is then developed. The effects of risk preferences as well as information asymmetry on the optimal bidding strategy are also examined. With particular references to the impacts of different numbers of bidding segments on the optimal bidding strategy, a numerical example is employed to demonstrate the validity of the proposed model and methodology. (author)

  13. COMPETITIVE BIDDING IN MEDICARE ADVANTAGE: EFFECT OF BENCHMARK CHANGES ON PLAN BIDS

    Science.gov (United States)

    Song, Zirui; Landrum, Mary Beth; Chernew, Michael E.

    2013-01-01

    Bidding has been proposed to replace or complement the administered prices in Medicare pays to hospitals and health plans. In 2006, the Medicare Advantage program implemented a competitive bidding system to determine plan payments. In perfectly competitive models, plans bid their costs and thus bids are insensitive to the benchmark. Under many other models of competition, bids respond to changes in the benchmark. We conceptualize the bidding system and use an instrumental variable approach to study the effect of benchmark changes on bids. We use 2006–2010 plan payment data from the Centers for Medicare and Medicaid Services, published county benchmarks, actual realized fee-for-service costs, and Medicare Advantage enrollment. We find that a $1 increase in the benchmark leads to about a $0.53 increase in bids, suggesting that plans in the Medicare Advantage market have meaningful market power. PMID:24308881

  14. Competitive bidding in Medicare Advantage: effect of benchmark changes on plan bids.

    Science.gov (United States)

    Song, Zirui; Landrum, Mary Beth; Chernew, Michael E

    2013-12-01

    Bidding has been proposed to replace or complement the administered prices that Medicare pays to hospitals and health plans. In 2006, the Medicare Advantage program implemented a competitive bidding system to determine plan payments. In perfectly competitive models, plans bid their costs and thus bids are insensitive to the benchmark. Under many other models of competition, bids respond to changes in the benchmark. We conceptualize the bidding system and use an instrumental variable approach to study the effect of benchmark changes on bids. We use 2006-2010 plan payment data from the Centers for Medicare and Medicaid Services, published county benchmarks, actual realized fee-for-service costs, and Medicare Advantage enrollment. We find that a $1 increase in the benchmark leads to about a $0.53 increase in bids, suggesting that plans in the Medicare Advantage market have meaningful market power. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. 48 CFR 14.202-8 - Electronic bids.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

  16. Particle swarm optimization based optimal bidding strategy in an ...

    African Journals Online (AJOL)

    In an electricity market generating companies and large consumers need suitable bidding models to maximize their profits. Therefore, each supplier and large consumer will bid strategically for choosing the bidding coefficients to counter the competitors bidding strategy. In this paper, bidding strategy problem modeled as an ...

  17. 48 CFR 14.202-1 - Bidding time.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

  18. Terror in the Board Room: The Bid-Opening Process

    Science.gov (United States)

    Shoop, James

    2009-01-01

    Competitive bids and the bid-opening process are the cornerstones of public school purchasing. The bid-opening process does not begin on the day of the bid opening. It begins with good planning by the purchasing agent to ensure that the advertised bid complies with the public school contracts law. In New Jersey, that raises the following…

  19. Impact of Contractors’ Bidding Strategies on Bid Success in the Nigeria Construction Industry

    Directory of Open Access Journals (Sweden)

    Tolulope Samuel Fawale

    2017-01-01

    Full Text Available Several types of researches have been carried out prior to the new millennium on the subject of bidding strategies in the construction industry. Today, organizations are faced with a very complex decision of bid/no-bid because it requires the assessment of large number of highly inter-related variables. The study aims at examining different types of Contractors’ Bidding Strategies (CBS with a view to determining their impact on bid success. In line with the aim, the study objectives include; evaluation of different types of CBS and; assessment of the success rate of contractors’ bid. The method of approach elicits information on the number of projects bided and successes recorded over a period of time. A total of one hundred and seventy-one useable responses were retrieved from questionnaire administration. Descriptive statistics, tables and percentages as well as mean item score (MIS were used for data analysis. The study showed that lowest bid, public relations and joint venture bidding strategies have great impact on contractors’ bid success especially on residential, educational and administrative projects in the Nigeria Construction Industry (NCI. Therefore, the study concluded that relationship exists between contractors’ bidding strategies and equivalent successes recorded over a period of time. It is important to also know that lowest bid strategy still remains the most effective bidding strategy for public works contracting in the NCI.

  20. 36 CFR 223.88 - Bidding methods.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.88... methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each sale will: (1) Insure open and fair competition, (2) Insure...

  1. 40 CFR 73.71 - Bidding.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Bidding. 73.71 Section 73.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Auctions, Direct Sales, and Independent Power Producers Written Guarantee § 73.71 Bidding...

  2. Competitive bidding might create antitrust problems

    International Nuclear Information System (INIS)

    Smith, D.J.

    1991-01-01

    With the increased use and complexity of competitive bidding systems for new generating capacity there is the possibility that federal antitrust laws may be violated. Anyone violating Section 1 of the Sherman Act could face stiff penalties. Falling into this category of violations are agreements among competitors, price fixing, and elimination of competitors through the allocations of customers and/or territories. It does not have to be in writing for someone to be charged with bid rigging. In fact, it is stated that bid rigging is typically proved from the testimony of one of the persons involved. According to this paper, a charge of rigging the bids can come from: One or more bidders offering to provide power at a higher price than another bidder. Two or more bidders offering to supply power at the same price. One or more potential bidders not submitting a bid or intentionally bidding high. One bidder and not the others offering a more favorable construction schedule or an alternative proposal. One firm offering to renegotiate if its bid is rejected while the other bidders refuse. These are just some of the agreements that are illegal. The penalties for such violations of the Sherman Act are severe: fines of up to $100,000 and up to three years in jail for individuals; up to $1 million in fines for corporations

  3. The Effect of Information Feedback in Construction Bidding

    Directory of Open Access Journals (Sweden)

    Alexander Soo

    2010-07-01

    Full Text Available  With the goal to achieve efficiency in bidding competitions, many codes of bidding procedure recommend clients provide contractors with bidding feedback information. Contractors strive to bid competitively via learning based on their experiences in past bidding attempts. The level of bidding feedback information, however, varies across clients. In many cases, clients do not provide feedback or provide insufficient feedback to contractors. Focussing on two information feedback conditions (full and partial, we examine: (i the changes in bidding trend over time, and (ii the effects of bidding feedback information on bidders’ competitiveness in bidding. Data were gathered using a bidding experiment that involved student (inexperienced bidders with a construction project management background. The results show that the variations in bids over time for full information feedback condition are statistically significant, but not for bids from bidders with partial bidding feedback information. Bidders with full bidding feedback information are more competitive than those with partial bidding feedback information. The findings add to both our theoretical and empirical understanding of construction bidding: an understanding of the process of changes in the price of building work, and how the process can be manipulated through the release of bidding feedback information.

  4. Marginal Bidding: An Application of the Equimarginal Principle to Bidding in TAC SCM

    Science.gov (United States)

    Greenwald, Amy; Naroditskiy, Victor; Odean, Tyler; Ramirez, Mauricio; Sodomka, Eric; Zimmerman, Joe; Cutler, Clark

    We present a fast and effective bidding strategy for the Trading Agent Competition in Supply Chain Management (TAC SCM). In TAC SCM, manufacturers compete to procure computer parts from suppliers (the procurement problem), and then sell assembled computers to customers in reverse auctions (the bidding problem). This paper is concerned only with bidding, in which an agent must decide how many computers to sell and at what prices to sell them. We propose a greedy solution, Marginal Bidding, inspired by the Equimarginal Principle, which states that revenue is maximized among possible uses of a resource when the return on the last unit of the resource is the same across all areas of use. We show experimentally that certain variations of Marginal Bidding can compute bids faster than our ILP solution, which enables Marginal Bidders to consider future demand as well as current demand, and hence achieve greater revenues when knowledge of the future is valuable.

  5. Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

    Science.gov (United States)

    Itkin, Tomer; Rafii, Shahin

    2017-09-11

    In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

  6. 48 CFR 14.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Rejection of individual... of individual bids. (a) Any bid that fails to conform to the essential requirements of the invitation... total price of the bid, but the prices for individual line items as well. (g) Any bid may be rejected if...

  7. 48 CFR 814.404-2 - Rejection of individual bids.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... nonresponsive an individual bid that is not in compliance with the Government's bid acceptance time, since...

  8. The Committee System For Competitive Bids In Local ...

    African Journals Online (AJOL)

    When a municipality contracts for goods or services, it must make use of competitive bidding / a public call for tenders for contracts over R200 000 as well as for long term contracts. A competitive bidding process generally consists of different stages, for example, compiling bid specifications, advertising the bid, the receipt ...

  9. 7 CFR 1955.147 - Sealed bid sales.

    Science.gov (United States)

    2010-01-01

    ... Law 103-354 will accept the bid or bids which are in the best financial interest of the Government... agency under Public Law 103-354 office. All bids will be date and time stamped. Advertisements and... 7 Agriculture 14 2010-01-01 2009-01-01 true Sealed bid sales. 1955.147 Section 1955.147...

  10. 7 CFR 1780.95 - Public bidding on bonds.

    Science.gov (United States)

    2010-01-01

    ... public bidding. The Agency will not submit a bid at the advertised sale unless required by State law, nor... 7 Agriculture 12 2010-01-01 2010-01-01 false Public bidding on bonds. 1780.95 Section 1780.95... Bonds and Bond Transcript Documents for Public Body Applicants § 1780.95 Public bidding on bonds. Bonds...

  11. 23 CFR 635.111 - Tied bids.

    Science.gov (United States)

    2010-04-01

    ... MAINTENANCE Contract Procedures § 635.111 Tied bids. (a) The STD may tie or permit the tying of Federal-aid...-financed highway projects may be combined in one contract if the conditions of the projects are so similar...

  12. Competitive bidding tactics for new exploration concessions

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, P.W.; Bramley, A.D.; Castellani, J.M. [Little (Arthur D.), London (United Kingdom)

    1994-12-31

    In some (mostly developing) countries, oil companies compete for new exploration agreements by bidding the key economic parameters. We believe that an increasing number of companies are making generous offers in order to win bids, in the expectation of being able to renegotiate economic terms if they make a discovery. However, the tactic damages the performance of the E and P industry in developing countries - for governments and companies alike. The means of combating `tactical overbidding` rests largely with governments and national oil companies in making better contracts and taking a cautious approach to the evaluation of bids. Reputable companies can contribute to the process by emphasising that their bids are formulated in good faith and based on sound commercial considerations. (author)

  13. Competitive bidding tactics for new exploration concessions

    International Nuclear Information System (INIS)

    Hawley, P.W.; Bramley, A.D.; Castellani, J.M.

    1994-01-01

    In some (mostly developing) countries, oil companies compete for new exploration agreements by bidding the key economic parameters. We believe that an increasing number of companies are making generous offers in order to win bids, in the expectation of being able to renegotiate economic terms if they make a discovery. However, the tactic damages the performance of the E and P industry in developing countries - for governments and companies alike. The means of combating 'tactical overbidding' rests largely with governments and national oil companies in making better contracts and taking a cautious approach to the evaluation of bids. Reputable companies can contribute to the process by emphasising that their bids are formulated in good faith and based on sound commercial considerations. (author)

  14. Bid Regulations in a Multi-unit Uniform Price Auction

    DEFF Research Database (Denmark)

    Boom, Anette

    for larger rms does not guarantee market prices below that cap. A suffciently high bid floor only for smaller firms destroys some or all pure strategy equilibria despite their prices being above the bid floor. With a general bid floor this happens only with considerably higher bid floors.......This paper examines the effect of bid regulations on the range of potential equilibrium prices in a multi-unit uniform price auction with heterogenous bidders. General bid caps destroy equilibria with prices above the bid cap and create new equilibria with prices way below the cap. A cap only...

  15. Political entrepreneurship and bidding for political monopoly

    OpenAIRE

    Michael Wohlgemuth

    2000-01-01

    An analytical framework for dealing with political entrepreneurship and reform is proposed which is based on some new combinations of Schumpeterian political economy, an extended version of Tullock's model of democracy as franchise-bidding for natural monopoly and some basic elements of New Institutional Economics. It is shown that problems of insufficient award criteria and incomplete contracts which may arise in economic bidding schemes, also - and even more so - characterise political comp...

  16. Europe wrestles with ITER site bid

    CERN Multimedia

    Feder, T

    2003-01-01

    "The European Union is in a quandary over whether to put forward the French or Spanish site to host ITER, a $5 billion magnetic fusion experiment intended to prove the feasability of fusion energy. The decision is set for 27 November, with the final site selection, between the victorious European bid and bids from Canada and Japan, to follow within a couple of months" (1 page)

  17. Ex vivo assays to study self-renewal, long-term expansion, and leukemic transformation of genetically modified human hematopoietic and patient-derived leukemic stem cells

    NARCIS (Netherlands)

    Sontakke, Pallavi; Carretta, Marco; Capala, Marta; Schepers, Hein; Schuringa, Jan Jacob

    2014-01-01

    With the emergence of the concept of the leukemic stem cell (LSC), assays to study them remain pivotal in understanding (leukemic) stem cell biology. Although the in vivo NOD-SCID or NSG xenotransplantation model is currently still the favored assay of choice in most cases, this system has some

  18. Bidding strategy in pay-as-bid markets based on supplier-market interaction analysis

    International Nuclear Information System (INIS)

    Bigdeli, N.; Afshar, K.; Fotuhi-Firuzabad, M.

    2010-01-01

    In this paper, a new bidding strategy for pay-as-bid market suppliers is introduced. This method is based on a systematic analysis of interactions of market with the suppliers via several market indices as well as forecasting important indices by artificial neural networks. Besides, the proposed method considers the practical limitations in the system and deals with incomplete information handling, closely. Next, a strategic bidding approach is proposed for optimal bidding by the suppliers. In these investigations, the paper focus is on the experimental situation of Iran electricity market as a pay-as-bid market and a sample generating company with several generating units from this market is considered as the benchmark. The results of applying this approach to this generating company are representative of good performance of the proposed method.

  19. Subsalt bids, strategies analyzed from Gulf of Mexico Sale 147

    International Nuclear Information System (INIS)

    Lerche, I.

    1994-01-01

    Analysis of the bid distributions for the 10 most expensively acquired blocks at the March 1994 Gulf of Mexico Lease Sale 147 indicates that the global distribution of bids splits into two groups at a bid of around $2 million. Both the low bid group--25 bids--and the high bid group--17 bids--follow approximately log normal distributions with different slopes. On an individual block basis, four blocks had sufficient numbers of bids (≥5) to indicate a statistical ''mix'' of low and high group bids, but no preference with respect to physical location of the blocks is apparent. On a corporate basis, two bidding groups--Amoco on its own or with partners, Anadarko on its own or with partners--each made a sufficient number of bids to indicate that both groups followed a very similar bidding pattern, both of which are approximately log normally distributed, but that the Amoco groups was systematically conservative relative to the Anadarko group. The paper discusses the overall distribution of bids, distribution by blocks, and bids by corporation

  20. Competitive bidding tactics for new exploration concessions

    International Nuclear Information System (INIS)

    Hawley, P.D.; Bramley, A.D.; Castellani, J.M.

    1992-01-01

    In some (mostly developing) countries, oil companies compete for new exploration agreements by bidding the key economic parameters. Companies are faced with a trade off between profitability of potential discoveries and probability of winning the bid. The authors believe that an increasing number of companies are making generous offers in order to win bids, in the expectation of being able to renegotiate economic terms if they make a discovery. This tactic is hard to recognize and may have a good chance of success, due to the strength of the oil company's bargaining position upon discovery. However, the tactic damages the performance of the E and P industry in developing countries --- for governments and companies alike. This paper reports that the means of combating tactical underbidding rest largely with governments and national oil companies in making better contracts and taking a cautious approach to the evaluation of bids. Reputable companies can contribute to the process by emphasizing that their bids are formulated in good faith and based on sound commercial considerations

  1. Modelling contractor’s bidding decision

    Directory of Open Access Journals (Sweden)

    Biruk Sławomir

    2017-03-01

    Full Text Available The authors aim to provide a set of tools to facilitate the main stages of the competitive bidding process for construction contractors. These involve 1 deciding whether to bid, 2 calculating the total price, and 3 breaking down the total price into the items of the bill of quantities or the schedule of payments to optimise contractor cash flows. To define factors that affect the decision to bid, the authors rely upon literature on the subject and put forward that multi-criteria methods are applied to calculate a single measure of contract attractiveness (utility value. An attractive contract implies that the contractor is likely to offer a lower price to increase chances of winning the competition. The total bid price is thus to be interpolated between the lowest acceptable and the highest justifiable price based on the contract attractiveness. With the total bid price established, the next step is to split it between the items of the schedule of payments. A linear programming model is proposed for this purpose. The application of the models is illustrated with a numerical example.

  2. Quantitative MR imaging of normal and leukemic bone marrow

    International Nuclear Information System (INIS)

    Hinks, R.S.; Dunlap, H.J.; Poon, P.Y.; Curtis, J.; Henkelman, R.M.

    1986-01-01

    The authors have developed and tested a protocol that allows extraction of reliable T1 and T2 relaxation times from imaging data. They have used these methods to study in vivo the bone marrow of healthy volunteers and patients with acute leukemia. Examinations were performed at 6.25 MHz using an interleaved ISE/SE sequence to calculate T1 and an eight echo (TE = 25) sequence to calculate T2. The results are summarized as follows: In leukemic patients, T1 = 476 +- 115 msec; in leukemic patients in remission, T1 = 290 +- 31 msec; in healthy volunteers, T1 = 329 +- 32 msec. The T2 values were not significantly different for the three groups (105 +- 10 msec). Work is underway to evaluate whether T1 values of bone marrow may be used to monitor patients in remission and to detect the onset of relapse

  3. Applicability Analysis of Bidding Strategy in Electricity Market

    Directory of Open Access Journals (Sweden)

    Zhou Suyan

    2017-01-01

    Full Text Available With the development of the electricity market, competition has been introduced in the generation side. It is the overall development trend of the electricity market reformulation to optimize the allocation of different resources through bidding. Therefore, it is significant to research the bidding strategies of the generation companies and the large consumers. This paper reviews the existing research methods of bidding strategy. According to the different market mechanisms, the market participators will choose different bidding strategies based on their own cases. We analyze the applicability of bidding strategies under the different conditions, and give suggestions on how to select bidding strategy for the different market participators under different conditions.

  4. Strategic Bidding Behaviors in Nondecreasing Sponsored Search Auctions

    Directory of Open Access Journals (Sweden)

    Chen-Kun Tsung

    2013-01-01

    Full Text Available To realize the specific results in the sponsored search auctions, most advertisers submit particular bid prices. The bidding behaviors with specific purposes are called as the strategic bidding. However, some strategic bidding behaviors will result in negative effects, such as the elimination of the equilibrium and the payment increase for some advertisers. The bidding behaviors with negative results are termed as the vindictive bidding. We survey four strategic bidding behaviors which include a rational bidding and three vindictive bidding strategies. In this paper, we study the relationship between the effects resulted by the vindictive bidding and the valuations of the vindictive advertisers. In our experiments, the search engine provider (SEP is benefited by all vindictive bidding behaviors, and the increment of the SEP's revenue is proportional to the degree of the vindictiveness. Bidding vindictively without sacrificing the own utility improves the advertiser's utility with high probability. Moreover, we observe that the SEP's revenue is improved by the following situations. First, the vindictive advertiser with low valuation in the keywords with high market value results in more SEP's revenue than that in the keywords with low market value. The second case is to raise the bidding competition between advertisers.

  5. Bidding in common value fair division games

    OpenAIRE

    Brünner, Tobias; Becker, Alice

    2013-01-01

    In a fair division game an indivisible object with an unknown common value is owned by a group of individuals and should be allocated to one of them while the others are compensated monetarily. Implementing fair division games in the lab, we fi nd many occurrences of the winner's curse under the first-price rule but only few occurrences under the second-price rule. Moreover, bidding behavior is very heterogeneous across subjects. A considerable share of our subjects anticipates that other bid...

  6. Single-Bid Awards Under the GSA Service Schedules

    National Research Council Canada - National Science Library

    Stott, Bethany

    2004-01-01

    This study seeks to examine the verity of the common perception that single-bid orders are more costly, lower in performance quality, and shorter in pre-award process time than competitively-bid orders...

  7. 48 CFR 14.202-4 - Bid samples.

    Science.gov (United States)

    2010-10-01

    ... be described adequately in the specification or purchase description. (2) Bid samples will be used... the bidder's intention was to qualify the bid. (See 14.404-2(d) if the qualification does not conform...

  8. Single-Bid Awards Under the GSA Service Schedules

    National Research Council Canada - National Science Library

    Stott, Bethany

    2004-01-01

    .... To this end, we look at why single-bid orders exist in the current procurement system, how these orders measure up to competitively-bid orders in cost and performance, and how customer satisfaction...

  9. Five bid to host Middle East synchroton

    CERN Multimedia

    McCabe, H

    1999-01-01

    Germany is willing to donate a synchrotron to a research centre to be built somewhere in the Middle East. Bids to host the centre were submitted by Turkey, Cyprus, Iran, the Palestinian Authority and Egypt. Funding of at least 30 million US dollars still needs to be found (1 page).

  10. 47 CFR 1.2103 - Competitive bidding design options.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Competitive bidding design options. 1.2103 Section 1.2103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2103 Competitive bidding design options. (a) The...

  11. 23 CFR 635.112 - Advertising for bids and proposals.

    Science.gov (United States)

    2010-04-01

    ... OPERATIONS CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.112 Advertising for bids and proposals. (a) No work shall be undertaken on any Federal-aid project, nor shall any project be advertised for bids... 23 Highways 1 2010-04-01 2010-04-01 false Advertising for bids and proposals. 635.112 Section 635...

  12. 48 CFR 52.228-1 - Bid Guarantee.

    Science.gov (United States)

    2010-10-01

    ... as accepted. (c) The amount of the bid guarantee shall be ____ percent of the bid price or $____, whichever is less. (d) If the successful bidder, upon acceptance of its bid by the Government within the period specified for acceptance, fails to execute all contractual documents or furnish executed bond(s...

  13. 47 CFR 25.403 - Bidding application and certification procedures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Bidding application and certification procedures. 25.403 Section 25.403 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Competitive Bidding Procedures for DARS § 25.403 Bidding...

  14. 48 CFR 731.771 - Bid and proposal costs.

    Science.gov (United States)

    2010-10-01

    ... GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Nonprofit Organizations 731.771 Bid and proposal costs. Pending the establishment of Government-wide principles in...) below, bid and proposal costs of the current accounting period of both successful and unsuccessful bids...

  15. Sustainable promotion nuclear power enterprise procurement bidding risk management

    International Nuclear Information System (INIS)

    Wu Yimin

    2014-01-01

    Nuclear power enterprise procurement bidding work faced with certain risk in recent years, the domestic nuclear power enterprises in the bidding work never stop research and explore the effective ways to guard against legal risks, and has made considerable progress, the eighteenth big country advocates the safety and efficiency of nuclear power development policy, in the face of the subsequent nuclear power construction projects have started, nuclear power enterprise bidding risk management work shoulder heavy responsibilities article through nuclear power enterprise procurement bidding risk management present situation, proposed the sustainable promotion nuclear power enterprise procurement bidding risk management countermeasures. (author)

  16. Developing Medicare Competitive Bidding: A Study of Clinical Laboratories

    Science.gov (United States)

    Hoerger, Thomas J.; Meadow, Ann

    1997-01-01

    Competitive bidding to derive Medicare fees promises several advantages over administered fee systems. The authors show how incentives for cost savings, quality, and access can be incorporated into bidding schemes, and they report on a study of the clinical laboratory industry conducted in preparation for a bidding demonstration. The laboratory industry is marked by variable concentration across geographic markets and, among firms themselves, by social and economic heterogeneity. The authors conclude that these conditions can be accommodated by available bidding design options and by careful selection of bidding markets. PMID:10180003

  17. Chromosomal Aberrations Associated with Clonal Evolution and Leukemic Transformation in Fanconi Anemia: Clinical and Biological Implications

    Directory of Open Access Journals (Sweden)

    Stefan Meyer

    2012-01-01

    Full Text Available Fanconi anaemia (FA is an inherited disease with congenital and developmental abnormalities, bone marrow failure, and extreme risk of leukemic transformation. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. Here, we review bone marrow findings in FA and discuss the clinical and biological implications of chromosomal aberrations associated with leukemic transformation.

  18. Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brune, D; Frykberg, B; Samsahl, K; Wester, P O

    1961-11-15

    By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed.

  19. Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Brune, D.; Frykberg, B.; Samsahl, K.; Wester, P.O.

    1961-11-01

    By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed

  20. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration

    Science.gov (United States)

    Dias, Sergio; Hattori, Koichi; Zhu, Zhenping; Heissig, Beate; Choy, Margaret; Lane, William; Wu, Yan; Chadburn, Amy; Hyjek, Elizabeth; Gill, Muhammad; Hicklin, Daniel J.; Witte, Larry; Moore, M.A.S.; Rafii, Shahin

    2000-01-01

    Emerging data suggest that VEGF receptors are expressed by endothelial cells as well as hematopoietic stem cells. Therefore, we hypothesized that functional VEGF receptors may also be expressed in malignant counterparts of hematopoietic stem cells such as leukemias. We demonstrate that certain leukemias not only produce VEGF but also express functional VEGFR-2 in vivo and in vitro, resulting in the generation of an autocrine loop that may support leukemic cell survival and proliferation. Approximately 50% of freshly isolated leukemias expressed mRNA and protein for VEGFR-2. VEGF165 induced phosphorylation of VEGFR-2 and increased proliferation of leukemic cells, demonstrating these receptors were functional. VEGF165 also induced the expression of MMP-9 by leukemic cells and promoted their migration through reconstituted basement membrane. The neutralizing mAb IMC-1C11, specific to human VEGFR-2, inhibited leukemic cell survival in vitro and blocked VEGF165-mediated proliferation of leukemic cells and VEGF-induced leukemic cell migration. Xenotransplantation of primary leukemias and leukemic cell lines into immunocompromised nonobese diabetic mice resulted in significant elevation of human, but not murine, VEGF in plasma and death of inoculated mice within 3 weeks. Injection of IMC-1C11 inhibited proliferation of xenotransplanted human leukemias and significantly increased the survival of inoculated mice. Interruption of signaling by VEGFRs, particularly VEGFR-2, may provide a novel strategy for inhibiting leukemic cell proliferation. PMID:10953026

  1. DOE turns down all bids for Elk Hills crude

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that the U.S. Department of Energy has rejected all bids submitted in the Mar. 5 semiannual sale of crude oil from Elk Hills Naval Petroleum Reserve (NPR-1) in California. DOE the all 19 bids for the 53,740 b/d of crude were too low. The bids ranged from $11.71 to $14.06/bbl, with the top bids for the highest quality Stevens zone crude averaging $13.25/bbl. California oil companies the they bid what the market would bear, explaining a surplus of Alaskan crude on the West Coast has driven down the price of local crudes, notably heavy crudes. DOE will extend the current oil purchase contracts through April while it issues a new request for bids. It planned to issue the solicitation Mar. 23 and receive bids Apr. 15

  2. Competitive bidding in Medicare: who benefits from competition?

    Science.gov (United States)

    Song, Zirui; Landrum, Mary Beth; Chernew, Michael E

    2012-09-01

    To conduct the first empirical study of competitive bidding in Medicare. We analyzed 2006-2010 Medicare Advantage data from the Centers for Medicare and Medicaid Services using longitudinal models adjusted for market and plan characteristics. A $1 increase in Medicare's payment to health maintenance organization (HMO) plans led to a $0.49 (P service plans included, higher Medicare payments increased bids less ($0.33 per dollar), suggesting more competition among these latter plans. As a market-based alternative to cost control through administrative pricing, competitive bidding relies on private insurance plans proposing prices they are willing to accept for insuring a beneficiary. However, competition is imperfect in the Medicare bidding market. As much as half of every dollar in increased plan payment went to higher bids rather than to beneficiaries. While having more insurers in a market lowered bids, the design of any bidding system for Medicare should recognize this shortcoming of competition.

  3. Research on bidding quotation game of international project

    Science.gov (United States)

    Lin, Tao; Xu, Xin

    2017-04-01

    Bidding competition of international projects is more and more fierce currently. However, China started late relatively in the field, it is still lack of experience in the aspect of participation in bidding of international projects, and more effective bidding quotation system is not formed till present. Therefore, China can not win through systemic bidding quotation methods compared with many powerful bidding enterprises in the international field. Research on the field is also focused by many aspects as a result. It is urgent to solve related problems. Game theory is combined for analyzing the effectiveness and operability of bidding quotation models mainly based on current situation of bidding market in China international projects during research process in the paper. The research starts with the perspective of bidders for analyzing their game with tenderers and other bidders. The results have operational value aiming at bidders.

  4. Risk analysis of bidding strategies in an electricity pay as bid auction: A new theorem

    International Nuclear Information System (INIS)

    Rahimiyan, Morteza; Rajabi Mashhadi, Habib

    2007-01-01

    Considering the uncertainties in the power market, the bidding problem has an important role for the power supplier to reach his goals, and using risk management methods to protect against the market risk is unavoidable. Thus, in this paper, the bidding decision making problem is formulated from a supplier's viewpoint in a spot market. The spot market works based on a pay as bid auction or a discriminatory price auction. The market clearing price (MCP) is uncertain, and we consider a probabilistic model for it. Regarding the literature of the bidding problem and forecasting methods of MCP, a normal probability density function, pdf (N(μ m , σ m )), is a proper distribution for the MCP. The statistical parameters of MCP vary on different times (peak and off peak), and considering the concept of supplier risk, their effects on the supplier expected benefit and expected sell from selling energy will be discussed analytically. An important section of this research work concerns the optimal bidding strategy when μ m and σ m vary in different conditions of the power market. Thus, the coefficient of variation index (CV), as a proper measure, mathematically defined as σ m divided by μ m , is introduced to measure the market risk index. In this paper, the CV index is used to analyze and manage the supplier risk and introduce the optimal strategy. Then, for a constant amount of the CV as a theorem, it is proved that: (1) the maximum of the expected sell occurs at a constant level of the supplier risk and (2) the optimal bid price linearly depends on the standard deviation of the MCP. This theorem is generalized for the case that the expected value of the supplier benefit is considered as an objective function in the bidding process. Some numerical examples are presented, and application of the proposed theorem is discussed

  5. Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Yeh, Su-Peng; Lo, Wen-Jyi; Lin, Chiao-Lin; Liao, Yu-Min; Lin, Chen-Yuan; Bai, Li-Yuan; Liang, Ji-An; Chiu, Chang-Fang

    2012-02-01

    Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only "cytogenetic remission" but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

  6. Cyanobacteria as a Source for Novel Anti-Leukemic Compounds.

    Science.gov (United States)

    Humisto, Anu; Herfindal, Lars; Jokela, Jouni; Karkman, Antti; Bjørnstad, Ronja; Choudhury, Romi R; Sivonen, Kaarina

    2016-01-01

    Cyanobacteria are an inspiring source of bioactive secondary metabolites. These bioactive agents are a diverse group of compounds which are varying in their bioactive targets, the mechanisms of action, and chemical structures. Cyanobacteria from various environments, especially marine benthic cyanobacteria, are found to be rich sources for the search for novel bioactive compounds. Several compounds with anticancer activities have been discovered from cyanobacteria and some of these have succeeded to enter the clinical trials. Varying anticancer agents are needed to overcome increasing challenges in cancer treatments. Different search methods are used to reveal anticancer compounds from natural products, but cell based methods are the most common. Cyanobacterial bioactive compounds as agents against acute myeloid leukemia are not well studied. Here we examined our new results combined with previous studies of anti-leukemic compounds from cyanobacteria with emphasis to reveal common features in strains producing such activity. We report that cyanobacteria harbor specific anti-leukemic compounds since several studied strains induced apoptosis against AML cells but were inactive against non-malignant cells like hepatocytes. We noted that particularly benthic strains from the Baltic Sea, such as Anabaena sp., were especially potential AML apoptosis inducers. Taken together, this review and re-analysis of data demonstrates the power of maintaining large culture collections for the search for novel bioactivities, and also how anti-AML activity in cyanobacteria can be revealed by relatively simple and low-cost assays.

  7. Bidding strategies in Brazilian electricity auctions

    International Nuclear Information System (INIS)

    Azevedo, Erick M.; Correia, Paulo B.

    2006-01-01

    Double bilateral contract auctions for electric energy purchase and sale occur in Brazil. These auctions present incomplete information and possess some subjectivity in relation to the future scenario of the Brazilian electric system, inserted in the agent's bids. In this work, a model using Bayes' rule and the game theory is proposed to aid the agent in its bid definition. Through the existing relations between the Conditional probabilities of Bayes' Rule, the model transforms beliefs into information. In this way, the absence of information is supplied and the problem is transformed into a game with complete information. The present study has no worries in terms of transmission constraints, since they are not usually considered in the bilateral contract auctions in Brazil. At the end, Nash equilibrium (NE) can be found through the expected payoff matrix of each agent. (author)

  8. Bidding behavior in a symmetric Chinese auction

    Directory of Open Access Journals (Sweden)

    Mauricio Benegas

    2015-01-01

    Full Text Available This paper purposes a symmetric all-pay auction where the bidders compete neither for an object nor the object itself but for a lottery on receive. That lottery is determined endogenously through the bids. This auction is known as chance auction or more popularly as Chinese auction. The model considers the possibility that for some bidders the optimal strategy is to bid zero and to rely on luck. It showed that bidders become less aggressive when the lottery satisfies a variational condition. It was also shown that luck factor is decisive to determine if the expected payoff in Chinese auction is bigger or smaller than expected payoff in standard all-pay auction.

  9. A New Paradigm to Address Bid Protests

    OpenAIRE

    Melese, Francois; Angelis, Diana; Coughlan, Peter; Franck, Raymond; Kidalov, Max; LaCivita, C.J.; Gates, William

    2010-01-01

    Sponsored Report (for Acquisition Research Program) Approved for public release distribution unlimited. The goal of this study is to offer senior decision-makers a useful framework to evaluate, articulate, and recommend modifications of the government''s bid protest policy to improve procurement outcomes. Most countries allow disappointed bidders to protest public procurement decisions as an oversight mechanism to minimize fraud and errors by procurement officials. The expectation is...

  10. Effects of Suboptimal Bidding in Combinatorial Auctions

    Science.gov (United States)

    Schneider, Stefan; Shabalin, Pasha; Bichler, Martin

    Though the VCG auction assumes a central place in the mechanism design literature, there are a number of reasons for favoring iterative combinatorial auction designs. Several promising ascending auction formats have been developed throughout the past few years based on primal-dual and subgradient algorithms and linear programming theory. Prices are interpreted as a feasible dual solution and the provisional allocation is interpreted as a feasible primal solution. iBundle( 3) (Parkes and Ungar 2000), dVSV (de Vries et al. 2007) and the Ascending Proxy auction (Ausubel and Milgrom 2002) result in VCG payoffs when the coalitional value function satisfies the buyer submodularity condition and bidders bid straightforward, which is an expost Nash equilibrium in that case. iBEA and CreditDebit auctions (Mishra and Parkes 2007) do not even require the buyer submodularity condition and achieve the same properties for general valuations. In many situations, however, one cannot assume bidders to bid straightforward and it is not clear from the theory how these non-linear personalized price auctions (NLPPAs) perform in this case. Robustness of auctions with respect to different bidding behavior is therefore a critical issue for any application. We have conducted a large number of computational experiments to analyze the performance of NLPPA designs with respect to different bidding strategies and different valuation models. We compare the results of NLPPAs to those of the VCG auction and those of iterative combinatorial auctions with approximate linear prices, such as ALPS (Bichler et al. 2009) and the Combinatorial Clock auction (Porter et al. 2003).

  11. Range war: IPALCO's bid for PSI resources

    International Nuclear Information System (INIS)

    Studness, C.M.

    1993-01-01

    IPALCO Enterprises Inc. announced a hostile, unsolicited bid to acquire PSI Resources on March 15. IPALCO's bid for PSI is aggressive and well thought out, which befits the strong incentive that it had to take action. Besides topping Cincinnati Gas ampersand Electric's offering price made late last year, IPALCO took the initiative on three other fronts. First, it filed a lawsuit in federal court in Indianapolis to block the merger between PSI and Cincinnati. The suit claims that the proposed merger violates Indiana law and that PSI and Cincinnati have made false and misleading statements about the benefits of their proposed merger. Second, IPALCO announced it will oppose the merger between PSI and Cincinnati in proceedings before Indiana regulators. Third, IPALCO said it plans to nominate a slate of five candidates to stand election for PSI's Board of Directors at the company's annual shareholders meeting this spring. However, these initiatives and IPALCO's accompanying appeal to Hoosier loyality are little more than diversionary tactics. In the final analysis, whether PSI merges with IPALCO or with Cincinnati will depend rather simply on who is willing to make the highest bid

  12. MANDATORY TAKEOVER BIDS ON ROMANIAN CAPITAL MARKET

    Directory of Open Access Journals (Sweden)

    Cristian GHEORGHE

    2017-05-01

    Full Text Available The Romanian Capital Market Law (Law no 297/2004 lays down rules regarding public offers (to buy or sell of securities admitted to trading on a regulated market. Such offers are not unknown in the general framework of companies’ regulations, i.e. Company Law no 31/1990. Actually a public limited liability company (joint stock company can use a public subscriptions (offering shares for sale to raise the registered capital for incorporation of the company or to increase the company’s share capital already established. But all such operations are voluntary decisions. The founders or the shareholders of the company are those who decide to launch a public subscriptions. Capital Market Law comes with something new and at least peculiar at first sight: mandatory takeover bid, meaning a mandatory public offer made by an offeror to the holders of the securities of a company (offeree to acquire all or some of those securities. Can someone be forced to buy securities on the regulated market? The Capital Market Law responds affirmatively, but only if such takeover bid follows or has as its objective the acquisition of control of the offeree company in accordance with national law. The takeover bid remains under supervision and authorization of the national authority of the Capital Market (FSA – Financial Supervisory Authority.

  13. Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

    International Nuclear Information System (INIS)

    Ristic, Biljana; Bosnjak, Mihajlo; Arsikin, Katarina; Mircic, Aleksandar; Suzin-Zivkovic, Violeta; Bogdanovic, Andrija; Perovic, Vladimir; Martinovic, Tamara; Kravic-Stevovic, Tamara; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2014-01-01

    We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. - Highlights: • Idarubicin induces autophagy in leukemic cell lines and primary leukemic cells. • Idarubicin induces autophagy by inhibiting mTOR in leukemic cells. • mTOR suppression by idarubicin is associated with AMPK activation and Akt blockade.

  14. Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Ristic, Biljana [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Bosnjak, Mihajlo [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Arsikin, Katarina [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Mircic, Aleksandar; Suzin-Zivkovic, Violeta [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Bogdanovic, Andrija [Clinic for Hematology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Belgrade (Serbia); Perovic, Vladimir [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Martinovic, Tamara; Kravic-Stevovic, Tamara; Bumbasirevic, Vladimir [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Trajkovic, Vladimir, E-mail: vtrajkovic@med.bg.ac.rs [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Harhaji-Trajkovic, Ljubica, E-mail: buajk@yahoo.com [Institute for Biological Research, University of Belgrade, Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade (Serbia)

    2014-08-01

    We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. - Highlights: • Idarubicin induces autophagy in leukemic cell lines and primary leukemic cells. • Idarubicin induces autophagy by inhibiting mTOR in leukemic cells. • mTOR suppression by idarubicin is associated with AMPK activation and Akt blockade.

  15. Improving the design of competitive bidding in Medicare Advantage.

    Science.gov (United States)

    Cawley, John H; Whitford, Andrew B

    2007-04-01

    In 2003, Congress passed the Medicare Prescription Drug, Improvement, and Modernization Act, which required that in 2006 the Centers for Medicare and Medicaid Services (CMS) implement a system of competitive bids to set payments for the Medicare Advantage program. Managed care plans now bid for the right to enroll Medicare beneficiaries. Data from the first year of bidding suggest that imperfect competition is limiting the success of the bidding system. This article offers suggestions to improve this system based on findings from auction theory and previous government-run auctions. In particular, CMS can benefit by adjusting its system of competitive bids in four ways: credibly committing to regulations governing bidding; limiting the scope for collusion, entry deterrence, and predatory behavior among bidders; adjusting how benchmark reimbursement rates are set; and accounting for asymmetric information among bidders.

  16. Electric power bidding model for practical utility system

    Directory of Open Access Journals (Sweden)

    M. Prabavathi

    2018-03-01

    Full Text Available A competitive open market environment has been created due to the restructuring in the electricity market. In the new competitive market, mostly a centrally operated pool with a power exchange has been introduced to meet the offers from the competing suppliers with the bids of the customers. In such an open access environment, the formation of bidding strategy is one of the most challenging and important tasks for electricity participants to maximize their profit. To build bidding strategies for power suppliers and consumers in the restructured electricity market, a new mathematical framework is proposed in this paper. It is assumed that each participant submits several blocks of real power quantities along with their bidding prices. The effectiveness of the proposed method is tested on Indian Utility-62 bus system and IEEE-118 bus system. Keywords: Bidding strategy, Day ahead electricity market, Market clearing price, Market clearing volume, Block bid, Intermediate value theorem

  17. Impact of Railroad Contracts on Grain Bids to Farmers

    OpenAIRE

    Steven D. Hanson; C. Phillip Baumel; Daniel Schnell

    1989-01-01

    The deregulation of railroads by the Staggers Rail Act of 1980 reversed nearly a century of prohibition of contracts between railroads shippers/receivers. This paper presents an analysis of the impact that railroad contracts have on grain bids to corn, wheat, and soybean farmers. The empirical results indicate that destination contracts had significant impacts on prices bid to corn and soybean farmers, while origin contracts had significant and large impacts on prices bid to wheat farmers.

  18. Applicability Analysis of Bidding Strategy in Electricity Market

    OpenAIRE

    Zhou Suyan; Chen Fei; Qiao Yahui; Zhang Wenzhe; Zhang Kaifeng; Yuan Kun; Dai Xuemei

    2017-01-01

    With the development of the electricity market, competition has been introduced in the generation side. It is the overall development trend of the electricity market reformulation to optimize the allocation of different resources through bidding. Therefore, it is significant to research the bidding strategies of the generation companies and the large consumers. This paper reviews the existing research methods of bidding strategy. According to the different market mechanisms, the market partic...

  19. Advertising and Sealed Bid Auctions in a Transshipment Game

    Science.gov (United States)

    1996-06-01

    distributors promote their sales by advertising . While the maximum quantity demanded by each customer is fixed and given, his bids on the various...brands are determined by the advertising and other promotional efforts. The bid response function for each consumer is supposed to be given and known. The...the optimal distribution of the product, and the bids of the consumers . A numerical example is provided and the solution routine is discussed.

  20. A 7 YEAR-7-MONTH OLD BOY WITH LEUKEMIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Ni Made Rini Suari

    2013-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Ocular problems in patient with leukemia which are called leukemic retinopathy and subhyaloid hemorrhage is one of its feature. Subhyaloid hemorrhage in children with acute lymphoblastic leukemia (ALL is rarely happened. We reported a boy 7 year 7 month old, complained sudden blurred vision on his both eyes and diagnosed with acute lymphoblastic leukemia. When patient had complained his vision, result of routine hematology showed anemia, thrombocytopenia, and leukocytosis. Treatment of leukemic retinopathy in this patient was supportive and causal therapy with transfusion of thrombocyte concentrate, hydration for leukocytosis, giving chemotherapy intrathecal methotrexate and systemic (vincristine, daunorubicin, L-asparginase. We found gradually undergone resolution of subhyaloid hemorrhages, visible flame shaped thin, and his vision recovered nearly completely to 6/6 OD and 6/20 OS /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  1. Strategic Bidding in Hybrid CPC/CPM Auctions

    OpenAIRE

    Yi Zhu; Kenneth C. Wilbur

    2008-01-01

    Websites increasingly allow advertisers to choose whether to bid for advertising on a per-impression or per-click basis. We present the first analysis of this new hybrid auction market. The conventional wisdom in this industry is that brand advertisers (e.g., Coca-Cola) will bid for impressions, while direct response advertisers (e.g., Amazon.com) will bid for clicks. We find that in an auction setting similar to that used by Facebook and Google, brand advertisers may have an incentive to bid...

  2. 48 CFR 14.406 - Receipt of an unreadable electronic bid.

    Science.gov (United States)

    2010-10-01

    ... an unreadable electronic bid. If a bid received at the Government facility by electronic data... electronic bid. 14.406 Section 14.406 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... bid as originally submitted; and (b) That the unreadable condition of the bid was caused by Government...

  3. 42 CFR 414.412 - Submission of bids under a competitive bidding program.

    Science.gov (United States)

    2010-10-01

    ... D of this part. (c) Furnishing of items. A bid must include all costs related to furnishing an item... capital, stock or profits of another supplier; (ii) A controlling interest exists if one or more of owners... controlling interest and each supplier which has an ownership or controlling interest in it. (3) Commonly...

  4. Review of US utility demand-side bidding programs

    International Nuclear Information System (INIS)

    Goldman, C.A.; Kito, M.S.

    1995-01-01

    In this study, we review utility experiences with demand-side management (DSM) bidding programs. Since 1987, about 35 US utilities have signed long-term contracts with developers of DSM resources (ie energy service companies and customers) to provide a quantity of demand and energy savings at specified prices. Total resource costs range between 5.4 and 8 cents/kWh for DSM bidding programs where complete information on program costs is available. Almost all DSM bidding programs have been cost-effective compared with the utility's own supply-side alternatives, although there is substantial disagreement regarding the value of these programs compared with the utility's own DSM programs. In most bidding programs, payments to bidders account for between 70 and 90% of total program costs. Variation in winning bid prices is influenced primarily by DSM bid ceiling prices, differences in the mix of measures and markets targeted by developers, and the degree of performance risk borne by the DSM developer. Bids targeting residential customers averaged 6.2 cents/kWh compared with about 5.0 cents/kWh for commercial/industrial bids. We also compared the costs of acquiring lighting savings in DSM bidding contracts with a sample of 20 utility sponsored commercial/industrial lighting programs. We found that, on average total resource costs were slightly higher in bidding programs (6.1 vs 5.6 cents/kWh), although ratepayers bear significantly less performance risk in bidding programs compared with traditional utility-sponsored DSM programs. (author)

  5. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    DEFF Research Database (Denmark)

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin

    2012-01-01

    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  6. The in-vitro study of human blood leukemic cells by pulsed NMR

    International Nuclear Information System (INIS)

    Zulkarnaen, M.; Munawir; Wibowo, Tono; Suyitno, Gogot

    1983-01-01

    The diagram of leukemic cells in human blood has been studied by using the NMR longitudinal relaxation technique. The observation was treated in whole blood, serum and blood cell. Every result was compared with previous observation and show that the values of the proton longitudinal relaxation in the leukemic whole blood almost twice or more that of normal blood, while in the serum and the blood cell, the values are nearly the same. (author)

  7. 41 CFR 102-38.225 - What are the additional requirements in the bid process?

    Science.gov (United States)

    2010-07-01

    ... OF PERSONAL PROPERTY Bids Acceptance of Bids § 102-38.225 What are the additional requirements in the bid process? All sales except fixed price sales must contain a certification of independent price...

  8. 48 CFR 536.213-371 - Bids that include options.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Bids that include options... Contracting for Construction 536.213-371 Bids that include options. (a) Subject to the limitations in paragraph (c) of this section, you may include options in contracts if it is in the Government's interest...

  9. Extending the bidding format to promote demand response

    International Nuclear Information System (INIS)

    Liu, Yanchao; Holzer, Jesse T.; Ferris, Michael C.

    2015-01-01

    We propose an extended bidding structure to allow more realistic demand characteristics and behaviors to be expressed via flexible bids. In today's ISO-run energy markets, demand bid formats are all separable over time. However, a significant and growing segment of demand can be shifted across time and therefore has no way to bid its true valuation of consumption. We propose additional bid types that allow deferrable, adjustable and storage-type loads to better express their value, and thus elicit demand response in the most natural way – via direct participation in the market. We show that the additional bid types are easily incorporated into the existing market with no technological barrier and that they preserve the market's efficiency and incentive-compatibility properties. Using real market data, we give a numerical demonstration that the extended bid format could substantially increase social welfare, and also present additional insight on storage expansion scenarios. - Highlights: • Three new bid types are proposed to enrich demand-side participation. • Time value of electricity demand can be clearly conveyed to central dispatcher. • The extended format preserves market efficiency and incentive compatibility. • Energy storage is most effective to neutralize price volatility, with a limitation.

  10. 7 CFR 1726.201 - Formal competitive bidding.

    Science.gov (United States)

    2010-01-01

    ... send invitations to bid only to persons or organizations on its QBL for the specific project (see... factors, other than lowest dollar amount of the bid, which are to be considered in evaluating the proposals of qualified bidders (e.g., power consumption, losses, etc.) must be stated in the “Notice and...

  11. 7 CFR 1726.202 - Informal competitive bidding.

    Science.gov (United States)

    2010-01-01

    ... persons or organizations on its qualified bidder list for the specific project (see § 1726.23). (b... a responsive bid. (d) Evaluation basis. Any factors, other than lowest dollar amount of the bid, which are to be considered in evaluating the proposals of qualified bidders (e.g., power consumption...

  12. Bidding: Getting the Best Price for School Foodservice.

    Science.gov (United States)

    DiBella, Cecilia M.

    1998-01-01

    Sharon (Massachusetts) Public Schools developed an alternative procurement process for school food services that complies with state public bidding laws while evading "low-bid" constraints. The new process features evaluative criteria covering nutrition education, community outreach, management expertise, site visits, and price…

  13. 48 CFR 245.7303 - Formal bid procedures.

    Science.gov (United States)

    2010-10-01

    ... descriptions attached. (d) In addition to mailing or delivering notice of the proposed sale to prospective... type of sale, i.e., sealed bid, spot bid, auction; and (G) The location of the property. (f) The plant..., signed by the witnessing Government representative. ...

  14. Bidding in sequential electricity markets: The Nordic case

    DEFF Research Database (Denmark)

    Boomsma, Trine Krogh; Juul, Nina; Fleten, Stein-Erik

    2014-01-01

    problem as a multi-stage stochastic program. We investigate whether higher risk exposure can explain the hesitation, often observed in practice, to bid into the balancing market, even in cases of higher expected price levels. Furthermore, we quantify the gain from coordinated bidding, and by deriving......For electricity market participants trading in sequential markets with differences in price levels and risk exposure, coordinated bidding is highly relevant. We consider a Nordic power producer who engages in the day-ahead spot market and the near real-time balancing market. In both markets......, clearing prices and dispatched volumes are unknown at the time of bidding. However, in the balancing market, the agent faces an additional risk of not being dispatched. Taking into account the sequential clearing of these markets and the gradual realization of market prices, we formulate the bidding...

  15. Bid Preparation and Evaluation for Nuclear Power Plant Project Management

    International Nuclear Information System (INIS)

    Mohd Idris Taib, Mohd Khairulezwan Abdul Manan and Nur Farizan Amadzun

    2011-01-01

    Bid preparation and evaluation is one of the main activities in Nuclear Power Plant Project management. International Atomic Energy Agency guide and Korean experience was studied for Malaysian requirement in realization of first Nuclear Power Plant. Several aspects shall be taken into consideration such as political scenario, financial capabilities, sitting, human resource, technologies, fuel supplies and decommissioning for long term exceeded hundred years. Bidding process and activities is proposed for our country requirement. The main activities included but unlimited to Bid Invitation Specification, Bid Evaluation Process, Technical Evaluation, Economic Bid Evaluation and Contracting. On the end of day, Malaysia need safe and reliable Nuclear Power Plant. Malaysian Economic Transformation Programme also get benefit from spin-off localization products and services as well as Technology Transfer Programme. (author)

  16. Bidding price analysis for competitive generators and large consumers

    International Nuclear Information System (INIS)

    Ping Wei; Luonan Chen; Hsiao Dong Chiang

    2005-01-01

    We present a new method to analyze the bidding price of each participant (power suppliers and large consumers) in a pay-as-bid market. The bidding price will be decomposed into a variety of components corresponding to five factors, such as the incremental values of the subject bidder's generation on the system operational costs, on the income or payment of other bidders, and on the binding tradable constraints, and the first-order approximation of the subjective participant's bidding price. From an economic viewpoint, each component provides useful information for participants to design the strategic planning. The advantages of the method include that the decomposition is well defined without assumptions and that each decomposition term has its own economical and/or engineering meaning. The proposed method is numerically verified through computer simulations on a three-bus example system and a modified IEEE 30-bus power system with both generator and large consumer bidding. (author)

  17. Understanding the unbundled utility conservation bidding proposal

    International Nuclear Information System (INIS)

    Joskow, P.L.

    1990-01-01

    For several years regulatory advisers have been engaged in controversy about the propriety of integrating energy conservation measures into the total resource planning processes of electric utilities, and of proposed methods of doing so in the competitive supply procurement programs which have been initiated by some utilities. Two prominent economists conceived a method for doing this in competitive bidding programs and at the same time overcoming objections to previous proposals which were based on perceived violations of basic economic principles. They explained their concept and its operation in an article published here in June of last year. In this article another economist subjects the concept to further analysis, identifying its essential elements, and point to inevitable results of their application

  18. Investors flock to Venezuelan bidding rounds

    International Nuclear Information System (INIS)

    Kielmas, M.

    1997-01-01

    The Venezuelan government has disproved the long-cherished oil industry mantra that low tax rates attract private sector investors. At a time when most company managements feel they need to collect balance sheet assets at any price. Venezuela is ensuring that it remains the upmarket not the bargain basement investor target. Despite offering some of the most punitive and complicated fiscal terms worldwide, a near certainty that taxes will rise in the future and state oil company control of the join ventures' operating committees, oil investors of all sizes cannot keep away. The third marginal field reactivation round, launched late last year attracted a staggering 259 companies, both foreign and local, which prequalified to bid. (Author)

  19. Determination of the Prosumer's Optimal Bids

    Science.gov (United States)

    Ferruzzi, Gabriella; Rossi, Federico; Russo, Angela

    2015-12-01

    This paper considers a microgrid connected with a medium-voltage (MV) distribution network. It is assumed that the microgrid, which is managed by a prosumer, operates in a competitive environment and participates in the day-ahead market. Then, as the first step of the short-term management problem, the prosumer must determine the bids to be submitted to the market. The offer strategy is based on the application of an optimization model, which is solved for different hourly price profiles of energy exchanged with the main grid. The proposed procedure is applied to a microgrid and four different its configurations were analyzed. The configurations consider the presence of thermoelectric units that only produce electricity, a boiler or/and cogeneration power plants for the thermal loads, and an electric storage system. The numerical results confirmed the numerous theoretical considerations that have been made.

  20. Effect of dioxin on normal and leukemic human hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Lambertenghi-Deliliers, G.; Soligo, D. [Univ. degli Studi, Milan (Italy). Dipt. die Ematologia, Ospedale Maggiore Policlinico IRCCS; Fracchiolla, N.S. [Ospedale Maggiore Policlinico IRCCS, Milan (Italy). Dipt. di Ematologia; Servida, F. [Fondazione Matarelli, Milan (Italy); Bertazzi, P.A. [Istituti Clinici di Perfezionamento, Milan (Italy). Dipt. di Medicina del Lavoro

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) arises from chlorination of phenolic substrates or from partial combustion of organic materials in the presence of chlorine sources. TCDD has a large number of biological effects such as long-lasting skin disease, cardiovascular disease, diabete and cancer. TCDD is the prototypical agonist of the aryl hydrocarbon receptor (AhR), a member of the erb-A family that also includes the receptors for steroids, thyroid hormones, peroxisome proliferators and retinoids. When bound to dioxin, the AhR can bind to DNA and alter the expression of some genes including cytokines and growth factors. In this study, we analyzed the effect of escalating doses of TCDD on human CD34{sup +} progenitor cells from the leukapheresis of normal donors stimulated with G-CSF as well as the human myeloid leukemic cell lines HL60 (promyelocytic leukemia) and K562 (chronic myelogenous leukemia). The possible specific modulation of gene expression induced by the TCDD exposure was then tested by means of microarray analyses.

  1. Pulmonary leukemic involvement: high-resolution computed tomography evaluation

    International Nuclear Information System (INIS)

    Oliveira, Ana Paola de; Marchiori, Edson; Souza Junior, Arthur Soares

    2004-01-01

    Objective: To evaluate the role of high-resolution computed tomography (HRCT) in patients with leukemia and pulmonary symptoms, to establish the main patterns and to correlate them with the etiology. Materials and Methods: This is a retrospective study of the HRCT of 15 patients with leukemia and pulmonary symptoms. The examinations were performed using a spatial high-resolution protocol and were analyzed by two independent radiologists. Results: The main HRCT patterns found were ground-glass opacity (n=11), consolidation (n=9), airspace nodules (n=3), septal thickening (n=3), tree-in-bud pattern (n=3), and pleural effusion (n=3). Pulmonary infection was the most common finding seen in 12 patients: bacterial pneumonia (n=6), fungal infection (n = 4), pulmonary tuberculosis (n=1) and viral infection (n=1). Leukemic pleural infiltration (n=1), lymphoma (n=1) and pulmonary hemorrhage (n=1) were detected in the other three patients. Conclusion: HRCT is an important tool that may suggest the cause of lung involvement, its extension and in some cases to guide invasive procedures in patients with leukemia. (author)

  2. 77 FR 20413 - Notice of Realty Action: Modified Competitive, Sealed-Bid Sale of Public Land in Clark County, NV

    Science.gov (United States)

    2012-04-04

    ...)(1)(i), a designated bidder is offered the right to meet the highest bid. Refusal or failure to meet... and the bid guarantee. Sealed bid envelopes must be clearly marked on the front lower left corner with ``Sealed Bid, BLM Land Sale, N-90450.'' The sealed bid envelope must contain the $20,000 bid guarantee, the...

  3. Economic evaluation of bids for nuclear power plants. 1999 edition

    International Nuclear Information System (INIS)

    2000-01-01

    The introduction of a nuclear power plant (NPP) in a country is a major undertaking for all entities involved. The necessary planning work and co-ordination of the different fields of interest, from the point of view of governments, authorities, industries, universities and of the general public, must be done on a long term basis. This IAEA report may help support the work of the utility in the bidding process, especially in the economic bid evaluation. The different methods, aspects and parameters described should be regarded as a guide. The report's target criterion of lowest levelised discounted electricity generation costs (LDEGC) is a very useful and practical way of ranking bids. In view of the huge investment needed, the owner's country must be fully committed to a nuclear programme. A nuclear programme also requires a guarantee of long term financing, which implies the provision of local and foreign contributions. The necessary staff for all of the various areas of a nuclear programme must be recruited and trained. Within the planning phase, the bid invitation specification (BIS) has to be prepared and sent out in order to receive bids for the scope of supply and services desired by the owner. The evaluation of the bids received from the suppliers in response to the BIS is a huge and long-term task. The evaluation process should lead to the selection of the best bidder and at least to the final decision on the partners constructing the NPP. The responsibility for the entire bidding process lies with the plant owner. For technology transfer, two requirements need to be satisfied: the owner needs a well established and experienced engineering capability, and the supplier must be ready to transfer the agreed technology in such a way as to support the project goals. During the bid evaluation process, all aspects of the technical, financial and contractual approaches must be considered. Nowadays, political, socioeconomic and public acceptance aspects play a

  4. The Committee System for Competitive Bids in Local Government

    Directory of Open Access Journals (Sweden)

    P Bolton

    2009-07-01

    Full Text Available When a municipality contracts for goods or services, it must make use of competitive bidding / a public call for tenders for contracts over R200 000 as well as for long term contracts. A competitive bidding process generally consists of different stages, for example, compiling bid specifications, advertising the bid, the receipt and evaluation of bids, and the award and implementation of the contract. The Municipal Supply Chain Management Regulations require a municipality’s Supply Chain Management Policy to provide for a committee system to oversee the different stages. Such committee system must, moreover, consist of at least a bid specification committee, a bid evaluation committee and a bid adjudication committee. Until recently, little attention has been given by the courts to the roles and composition of the different committees in the committee system. It is only after government, and in particular, municipalities have begun to implement the committee system in their procurement processes that it is evident that problems are arising. In recent months, the courts have increasingly had to deal with issues pertaining to the implementation of the committee system.In this article, the relevant legislative provisions on the committee system for competitive bids in local government are discussed. The functions of each committee are explained and all the cases that have thus far involved the implementation of the committee system are critically analysed. Much attention is given to the cases since they serve as a warning to municipalities to uphold and comply with the rules relating to the roles and composition of the different committees. The cases illustrate how important it is for municipalities to ensure that the different committees are properly constituted and that decisions at meetings are properly taken. They also highlight the importance of the supervisory role of the municipal manager over the different committees. In light of the

  5. Economic evaluation of bids for nuclear power plants

    International Nuclear Information System (INIS)

    1976-01-01

    The purpose of the guidebook is to assist an organisation responsible for a nuclear power project in evaluating and establishing an economic order of merit among competing bids. An approximate overall time schedule for a first nuclear power plant project is provided. A schematic outline of technical bid evaluation is given. The basic procedure of economic bid evaluation is outlined, e.g. evaluation of the present worth of all cost items of plant capital investment, of the nuclear cycle, of O and M costs (operation and maintenance costs), and of economic corrections. All these cost items are evaluated for the economic life of the plant and corrected for escalation where applicable

  6. Competitive bidding for independent power: developments in the United States

    International Nuclear Information System (INIS)

    Kliman, M.

    1995-01-01

    In the United States electric utilities are using competitive bidding programs to procure power supplies from non-utility generators and, in some cases, to establish contracts with energy service companies for the implementation of demand-side management projects. Such programs are viewed as a path to efficient contracts in the private power industry. But bidding programs are complex, subject to pitfalls, and are developing very quickly. This paper reports on that development as of the early 1990s and, as an illustration, briefly describes and analyzes the bidding program of an electric utility in the State of New York. (author). 2 tabs

  7. Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells.

    Directory of Open Access Journals (Sweden)

    Jérome Kluza

    Full Text Available Challenges today concern chronic myeloid leukemia (CML patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention.

  8. Cannabidiol Reduces Leukemic Cell Size – But Is It Important?

    Science.gov (United States)

    Kalenderoglou, Nikoletta; Macpherson, Tara; Wright, Karen L.

    2017-01-01

    The anti-cancer effect of the plant-derived cannabinoid, cannabidiol, has been widely demonstrated both in vivo and in vitro. However, this body of preclinical work has not been translated into clinical use. Key issues around this failure can be related to narrow dose effects, the cell model used and incomplete efficacy. A model of acute lymphoblastic disease, the Jurkat T cell line, has been used extensively to study the cannabinoid system in the immune system and cannabinoid-induced apoptosis. Using these cells, this study sought to investigate the outcome of those remaining viable cells post-treatment with cannabidiol, both in terms of cell size and tracking any subsequent recovery. The phosphorylation status of the mammalian Target of Rapamycin (mTOR) signaling pathway and the downstream target ribosomal protein S6, were measured. The ability of cannabidiol to exert its effect on cell viability was also evaluated in physiological oxygen conditions. Cannabidiol reduced cell viability incompletely, and slowed the cell cycle with fewer cells in the G2/M phase of the cell cycle. Cannabidiol reduced phosphorylation of mTOR, PKB and S6 pathways related to survival and cell size. The remaining population of viable cells that were cultured in nutrient rich conditions post-treatment were able to proliferate, but did not recover to control cell numbers. However, the proportion of viable cells that were gated as small, increased in response to cannabidiol and normally sized cells decreased. This proportion of small cells persisted in the recovery period and did not return to basal levels. Finally, cells grown in 12% oxygen (physiological normoxia) were more resistant to cannabidiol. In conclusion, these results indicate that cannabidiol causes a reduction in cell size, which persists post-treatment. However, resistance to cannabidiol under physiological normoxia for these cells would imply that cannabidiol may not be useful in the clinic as an anti-leukemic agent. PMID

  9. Cannabidiol Reduces Leukemic Cell Size - But Is It Important?

    Science.gov (United States)

    Kalenderoglou, Nikoletta; Macpherson, Tara; Wright, Karen L

    2017-01-01

    The anti-cancer effect of the plant-derived cannabinoid, cannabidiol, has been widely demonstrated both in vivo and in vitro . However, this body of preclinical work has not been translated into clinical use. Key issues around this failure can be related to narrow dose effects, the cell model used and incomplete efficacy. A model of acute lymphoblastic disease, the Jurkat T cell line, has been used extensively to study the cannabinoid system in the immune system and cannabinoid-induced apoptosis. Using these cells, this study sought to investigate the outcome of those remaining viable cells post-treatment with cannabidiol, both in terms of cell size and tracking any subsequent recovery. The phosphorylation status of the mammalian Target of Rapamycin (mTOR) signaling pathway and the downstream target ribosomal protein S6, were measured. The ability of cannabidiol to exert its effect on cell viability was also evaluated in physiological oxygen conditions. Cannabidiol reduced cell viability incompletely, and slowed the cell cycle with fewer cells in the G2/M phase of the cell cycle. Cannabidiol reduced phosphorylation of mTOR, PKB and S6 pathways related to survival and cell size. The remaining population of viable cells that were cultured in nutrient rich conditions post-treatment were able to proliferate, but did not recover to control cell numbers. However, the proportion of viable cells that were gated as small, increased in response to cannabidiol and normally sized cells decreased. This proportion of small cells persisted in the recovery period and did not return to basal levels. Finally, cells grown in 12% oxygen (physiological normoxia) were more resistant to cannabidiol. In conclusion, these results indicate that cannabidiol causes a reduction in cell size, which persists post-treatment. However, resistance to cannabidiol under physiological normoxia for these cells would imply that cannabidiol may not be useful in the clinic as an anti-leukemic agent.

  10. 48 CFR 52.214-5 - Submission of Bids.

    Science.gov (United States)

    2010-10-01

    ... authorized by the solicitation. (e) Bids submitted by electronic commerce shall be considered only if the electronic commerce method was specifically stipulated or permitted by the solicitation. (End of provision...

  11. 48 CFR 14.301 - Responsiveness of bids.

    Science.gov (United States)

    2010-10-01

    ... conditions that do not vary from the terms and conditions of the invitation. (e) Bids submitted by electronic commerce shall be considered only if the electronic commerce method was specifically stipulated or...

  12. Hiding information in open auctions with jump bids

    Czech Academy of Sciences Publication Activity Database

    Ettinger, D.; Michelucci, Fabio

    2016-01-01

    Roč. 126, č. 594 (2016), s. 1484-1502 ISSN 0013-0133 Institutional support: RVO:67985998 Keywords : hiding information * open auctions * jump bids Subject RIV: AH - Economics Impact factor: 2.608, year: 2016

  13. Engineer’s estimate reliability and statistical characteristics of bids

    Directory of Open Access Journals (Sweden)

    Fariborz M. Tehrani

    2016-12-01

    Full Text Available The objective of this report is to provide a methodology for examining bids and evaluating the performance of engineer’s estimates in capturing the true cost of projects. This study reviews the cost development for transportation projects in addition to two sources of uncertainties in a cost estimate, including modeling errors and inherent variability. Sample projects are highway maintenance projects with a similar scope of the work, size, and schedule. Statistical analysis of engineering estimates and bids examines the adaptability of statistical models for sample projects. Further, the variation of engineering cost estimates from inception to implementation has been presented and discussed for selected projects. Moreover, the applicability of extreme values theory is assessed for available data. The results indicate that the performance of engineer’s estimate is best evaluated based on trimmed average of bids, excluding discordant bids.

  14. Invitation and Evaluation of Bids for Nuclear Power Plants

    International Nuclear Information System (INIS)

    2011-01-01

    This publication emphasizes the integrity and interdependence of various activities related to the bid invitation, technical and economic evaluation and contracting, it updates information included in the existing IAEA documents in order to better reflect the developments in the nuclear and energy industry, compiles a more compact and user friendly guidebook integrating the existing IAEA documents on the subject. It provides the necessary information to organize, guide and realize the activities related to the invitation, the technical and economic evaluation of bids, and contracting as an integrated process. Furthermore, this publication indicates how and to what degree the activities preceding the preparation of the bid invitation specification, the evaluation of bids and contracting could influence the process.

  15. Hiding information in open auctions with jump bids

    Czech Academy of Sciences Publication Activity Database

    Ettinger, D.; Michelucci, Fabio

    2016-01-01

    Roč. 126, č. 594 (2016), s. 1484-1502 ISSN 0013-0133 Institutional support: PRVOUK-P23 Keywords : hiding information * open auctions * jump bids Subject RIV: AH - Economics Impact factor: 2.608, year: 2016

  16. 25 CFR 163.17 - Deposit with bid.

    Science.gov (United States)

    2010-04-01

    ... submit a written request to have their bids considered for acceptance will be retained pending acceptance... damages available under applicable law or terms of the contract. (f) In the event of an administrative...

  17. Strategic bidding in electricity markets using particle swarm optimization

    International Nuclear Information System (INIS)

    Yucekaya, Ahmet D.; Valenzuela, Jorge; Dozier, Gerry

    2009-01-01

    Profit maximization for power companies is highly related to the bidding strategies used. In order to sell electricity at high prices and maximize profit, power companies need suitable bidding models that consider power operating constraints and price uncertainty within the market. In this paper, we present two particle swarm optimization (PSO) algorithms to determine bid prices and quantities under the rules of a competitive power market. The first method uses a conventional PSO technique to find solutions. The second method uses a decomposition technique in conjunction with the PSO approach. This new decomposition-based PSO dramatically outperforms the conventional form of PSO. We show that for nonlinear cost functions PSO solutions provide higher expected profits than marginal cost-based bidding. (author)

  18. Particle swarm optimization based optimal bidding strategy in an ...

    African Journals Online (AJOL)

    user

    A considerable amount of work has also been reported on the game theory applications ... probability distribution function (Song et al, 1999) and as a continuous ..... compared with GA and Monte Carlo method, therefore the bidding strategies.

  19. Financing power facilities in the competitive bidding environment

    International Nuclear Information System (INIS)

    Hills, A.L.

    1993-01-01

    In 1988 the Federal Energy Regulatory Commission (open-quote FERC close-quote) issued proposed rules and guidelines for the use of competitive bidding by state utility commissions to chose new power supplies. Since then, more than 20 states have implemented bidding programs to determine the price and sources of incremental generating capacity. This presentation discusses the impact of the use of competitive bidding on how landers and equity investors perceive the risks of project-supported financing arrangements and describes the actions that project developers have taken to adapt the project financing process to win bidding contests and as importantly, successfully obtain project financing in spite of the open-quotes credit crunchclose quotes market environment

  20. An evidence for adhesion-mediated acquisition of acute myeloid leukemic stem cell-like immaturities

    International Nuclear Information System (INIS)

    Funayama, Keiji; Shimane, Miyuki; Nomura, Hitoshi; Asano, Shigetaka

    2010-01-01

    For long-term survival in vitro and in vivo of acute myeloid leukemia cells, their adhesion to bone marrow stromal cells is indispensable. However, it is still unknown if these events are uniquely induced by the leukemic stem cells. Here we show that TF-1 human leukemia cells, once they have formed a cobblestone area by adhering to mouse bone marrow-derived MS-5 cells, can acquire some leukemic stem cell like properties in association with a change in the CD44 isoform-expression pattern and with an increase in a set of related microRNAs. These findings strongly suggest that at least some leukemia cells can acquire leukemic stem cell like properties in an adhesion-mediated stochastic fashion.

  1. Acute Respiratory Distress Syndrome Caused by Leukemic Infiltration of the Lung

    Directory of Open Access Journals (Sweden)

    Yao-Kuang Wu

    2008-05-01

    Full Text Available Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.

  2. An evidence for adhesion-mediated acquisition of acute myeloid leukemic stem cell-like immaturities

    Energy Technology Data Exchange (ETDEWEB)

    Funayama, Keiji; Shimane, Miyuki; Nomura, Hitoshi [Department of Integrative Bioscience and Biomedical Engineering, Waseda University, 4-3-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Asano, Shigetaka, E-mail: asgtkmd@waseda.jp [Department of Integrative Bioscience and Biomedical Engineering, Waseda University, 4-3-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan)

    2010-02-12

    For long-term survival in vitro and in vivo of acute myeloid leukemia cells, their adhesion to bone marrow stromal cells is indispensable. However, it is still unknown if these events are uniquely induced by the leukemic stem cells. Here we show that TF-1 human leukemia cells, once they have formed a cobblestone area by adhering to mouse bone marrow-derived MS-5 cells, can acquire some leukemic stem cell like properties in association with a change in the CD44 isoform-expression pattern and with an increase in a set of related microRNAs. These findings strongly suggest that at least some leukemia cells can acquire leukemic stem cell like properties in an adhesion-mediated stochastic fashion.

  3. Common Agency and Coordinated Bids in Sponsored Search Auctions

    OpenAIRE

    Maris Goldmanis; Antonio Penta; Francesco Decarolis

    2012-01-01

    As auctions are becoming the main mechanism for selling advertisement space on the web, marketing agencies specialized in bidding in online auctions are proliferating. We analyze theoretically how bidding delegation to a common marketing agency can undermine both revenues and efficiency of the generalized second price auction, the format used by Google and Microsoft-Yahoo!. Our characterization allows us to quantify the revenue losses relative to both the case of full competition and the case...

  4. Wind power bidding in electricity markets with high wind penetration

    International Nuclear Information System (INIS)

    Vilim, Michael; Botterud, Audun

    2014-01-01

    Highlights: • We analyze the pricing systems and wind power trading in electricity markets. • We propose a model that captures the relation between market prices and wind power. • A probabilistic bidding model can increase profits for wind power producers. • Profit maximizing bidding strategies carry risks for power system operators. • We conclude that modifications of current market designs may be needed. - Abstract: Objective: The optimal day-ahead bidding strategy is studied for a wind power producer operating in an electricity market with high wind penetration. Methods: A generalized electricity market is studied with minimal assumptions about the structure of the production, bidding, or consumption of electricity. Two electricity imbalance pricing schemes are investigated, the one price and the two price scheme. A stochastic market model is created to capture the price effects of wind power production and consumption. A bidding algorithm called SCOPES (Supply Curve One Price Estimation Strategy) is developed for the one price system. A bidding algorithm called MIMICS (Multivariate Interdependence Minimizing Imbalance Cost Strategy) is developed for the two price system. Results: Both bidding strategies are shown to have advantages over the assumed “default” bidding strategy, the point forecast. Conclusion: The success of these strategies even in the case of high deviation penalties in a one price system and the implicit deviation penalties of the two price system has substantial implications for power producers and system operators in electricity markets with a high level of wind penetration. Practice implications: From an electricity market design perspective, the results indicate that further penalties or regulations may be needed to reduce system imbalance

  5. Optimal Bidding Strategy for Renewable Microgrid with Active Network Management

    Directory of Open Access Journals (Sweden)

    Seung Wan Kim

    2016-01-01

    Full Text Available Active Network Management (ANM enables a microgrid to optimally dispatch the active/reactive power of its Renewable Distributed Generation (RDG and Battery Energy Storage System (BESS units in real time. Thus, a microgrid with high penetration of RDGs can handle their uncertainties and variabilities to achieve the stable operation using ANM. However, the actual power flow in the line connecting the main grid and microgrid may deviate significantly from the day-ahead bids if the bids are determined without consideration of the real-time adjustment through ANM, which will lead to a substantial imbalance cost. Therefore, this study proposes a formulation for obtaining an optimal bidding which reflects the change of power flow in the connecting line by real-time adjustment using ANM. The proposed formulation maximizes the expected profit of the microgrid considering various network and physical constraints. The effectiveness of the proposed bidding strategy is verified through the simulations with a 33-bus test microgrid. The simulation results show that the proposed bidding strategy improves the expected operating profit by reducing the imbalance cost to a greater degree compared to the basic bidding strategy without consideration of ANM.

  6. Strategies in responding to a hostile takeover bid

    International Nuclear Information System (INIS)

    Shaw, R.

    1997-01-01

    This paper examines the steps to be taken by a corporation and its board in order to be properly prepared before a hostile takeover bid is made. The procedures and steps to be followed in responding to a bid with a view to maximizing value for shareholders are also outlined. Reasons why a company may become target for a hostile takeover bid are reviewed, followed by a more detailed examination of the responsibilities of a board in responding to a takeover bid. These responsibilities include the adoption of a shareholders' rights plan ('poison pill'), review of executive employment contracts, making sure that a corporate indemnification agreement and directors' and officers' liability insurance plan are in place, implementation of structural deterrents, investor communication plans, preparing the 'black book', creating or updating the list of 'white knights', designating a data room, entering into confidentiality agreements with white knights, preparation of a response timetable, review of recent takeover bids, strategies for dealing with hostile bidders, strategies for enticing one or more a white knights to enter the bidding. Sample copy of a confidentiality agreement is contained in Schedule A. A list of break-up fees in recent Canadian mergers and acquisitions transactions is provided in Schedule B. 24 refs

  7. Strategic bidding for wind power producers in electricity markets

    International Nuclear Information System (INIS)

    Sharma, Kailash Chand; Bhakar, Rohit; Tiwari, H.P.

    2014-01-01

    Highlights: • Game theoretic bidding strategy approach developed to optimize wind power producers bids. • Rival behavior modeled through Stochastic Cournot model. • Location based dual imbalance price mechanism proposed to obtain imbalance charges. • Proposed approach evaluated using two realistic case studies. • Proposed approach increases profit of strategic wind power producers significantly. - Abstract: In evolving electricity markets, wind power producers (WPPs) would increase their profit through strategic bidding. However, generated power by WPPs is highly random, which may result into heavy imbalance charges. In markets dominated by wind generators, they would optimize their offered bids, considering rival behavior. In oligopolistic day-ahead electricity markets, this strategic behavior can be represented as a Stochastic Cournot model. Wind uncertainty is represented by scenarios generated using Auto Regressive Moving Average (ARMA) model. With a consideration of wind power uncertainty and imbalance charges, strategic WPPs can maximize their expected payoff or profit through the proposed Nash equilibrium based bidding strategy. Nash equilibrium is obtained using payoff matrix approach. Proposed approach is evaluated on two realistic case studies considering different technical constraints. Obtained results shows that proposed bidding strategy mechanism offers quantum increase in profit for WPPs, when their behavior is modeled in a game theoretic framework. Flexibility of approach offers opportunities for its extension to associated challenges

  8. The U.S. Agency-Level Bid Protest Mechanism: A Model for Bid Challenge Procedures in Developing Nations

    National Research Council Canada - National Science Library

    Troff, Erik A

    2005-01-01

    ... comply with established procurement rules. The decisive question for a developing nation is which of the available structural options best integrates the essential elements of an effective bid protest system in the context of existing legal...

  9. An antigen shared by human granulocytes, monocytes, marrow granulocyte precursors and leukemic blasts.

    Science.gov (United States)

    Shumak, K H; Rachkewich, R A

    1983-01-01

    An antibody to human granulocytes was raised in rabbits by immunization with granulocytes pretreated with rabbit antibody to contaminating antigens. The antibody reacted not only with granulocytes but also with monocytes and bone marrow granulocyte precursors including colony-forming units in culture (CFU-C). In tests with leukemic cells, the antibody reacted with blasts from most (8 of 9) patients with acute myelomonoblastic leukemia and from some patients with acute myeloblastic leukemia, morphologically undifferentiated acute leukemia and chronic myelogenous leukemia in blast crisis. The antibody did not react with blasts from patients with acute lymphoblastic leukemia nor with leukemic cells from patients with chronic lymphocytic leukemia.

  10. Analysis of the surface membrane of iodinated leukemic cells by SDS-polyacrylamide gel electrophoresis

    International Nuclear Information System (INIS)

    Ishitani, Kunihiko; Ikeda, Akira; Tamura, Minoru; Takeuchi, Hidekazu; Ihara, Koji

    1980-01-01

    Surface proteins of human leukemic cells were labeled selectively by lactoperoxydase catalysed-iodination and examined by SDS-polyacrylamide gel electrophoresis. The electrophoretic pattern of the surface membranes of cells from a patients with chronic mylogeneous leukemia in blast crisis was of B cell type and showed Ia like antigen. Leukemic cells from a patient with hairly cell leukemia also expressed the pattern of B cell type when tested by this method the technique of iodinating cell surface with lactoperoxidase is useful in characterization of leukemia cells for diagnosis and monitoring of clinical course. (author)

  11. IN SILICO MODELLING OF CYTOTOXIC BEHAVIOUR OF ANTI-LEUKEMIC COMPOUNDS ON HL-60 CELL LINE

    Directory of Open Access Journals (Sweden)

    David Ebuka Arthur

    2016-05-01

    Full Text Available This research employs multiple linear regression technique in the modelling of some potent anti-leukemic compounds using paDEL molecular descriptor software calculator, to identify the best relationship between the chemical structure and toxicities of the anticancer datasets against some leukemic cell lines (HL-60. Statistical parameters such as Q2 and R2pred (test set were computed to validate the strength of the model, while Williams plot was used to assess its applicability domain. The mean effects of the molecular descriptors in the models were calculated to illuminate the principal properties of the molecules responsible for their cytotoxicity.

  12. Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Beer, Philip A; Ortmann, Christina A; Stegelmann, Frank

    2010-01-01

    Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia......, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL...

  13. Improve The Capacity Of Competition About The Financial In The Bid Construction

    Directory of Open Access Journals (Sweden)

    Xuan Nam Chu

    2017-10-01

    Full Text Available According to experts enhancing competitiveness is an important solution for enterprises to build competitive capacity in bidding deciding the majority of win or lose in bidding. A good contractor can be eliminated in the first round because the bid does not meet the requirements of the investor. In order to have a good quality of bids enterprises should pay attention to the following tasks organizing the preparation of bidding dossiers setting the bidding prices selecting the optimum construction methods and work implementation plans. after bidding. Improving the quality of the bid preparation process should start from improving the quality of the staff in charge of bidding. At present the experience of bidding of many enterprises is limited especially the experience of working with foreign investors. Therefore businesses need to build a team of qualified professionals in the field of bidding. The training and professional fostering in this field should be carried out annually. They focus on foreign languages informatics knowledge of law and knowledge on international bidding. This is considered important preparatory steps that enterprises want to improve their competitiveness when participating in bidding especially participation in bidding packages using international donors and bidding packages cannot ignore it.

  14. Molecular dynamics study of lipid bilayers modeling the plasma membranes of normal murine thymocytes and leukemic GRSL cells.

    Science.gov (United States)

    Andoh, Yoshimichi; Okazaki, Susumu; Ueoka, Ryuichi

    2013-04-01

    Molecular dynamics (MD) calculations for the plasma membranes of normal murine thymocytes and thymus-derived leukemic GRSL cells in water have been performed under physiological isothermal-isobaric conditions (310.15K and 1 atm) to investigate changes in membrane properties induced by canceration. The model membranes used in our calculations for normal and leukemic thymocytes comprised 23 and 25 kinds of lipids, respectively, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. The mole fractions of the lipids adopted here were based on previously published experimental values. Our calculations clearly showed that the membrane area was increased in leukemic cells, and that the isothermal area compressibility of the leukemic plasma membranes was double that of normal cells. The calculated membranes of leukemic cells were thus considerably bulkier and softer in the lateral direction compared with those of normal cells. The tilt angle of the cholesterol and the conformation of the phospholipid fatty acid tails both showed a lower level of order in leukemic cell membranes compared with normal cell membranes. The lateral radial distribution function of the lipids also showed a more disordered structure in leukemic cell membranes than in normal cell membranes. These observations all show that, for the present thymocytes, the lateral structure of the membrane is considerably disordered by canceration. Furthermore, the calculated lateral self-diffusion coefficient of the lipid molecules in leukemic cell membranes was almost double that in normal cell membranes. The calculated rotational and wobbling autocorrelation functions also indicated that the molecular motion of the lipids was enhanced in leukemic cell membranes. Thus, here we have demonstrated that the membranes of thymocyte leukemic cells are more disordered and more fluid than normal cell membranes. Copyright © 2013

  15. Positive /sup 111/In-granulocyte scintigraphy in a patient with focal leukemic blast cell infiltrations

    Energy Technology Data Exchange (ETDEWEB)

    Syrjaelae, M; Remes, K; Paavonen, T; Liewendahl, K

    1985-06-01

    A patient with acute myeloid leukemia was investigated with /sup 111/In-granulocyte scintigraphy to reveal possible sites of infection. /sup 111/In-granulocytes accumulated in areas of leukemia blast cell infiltration leading to a false-positive scintigram. This possibility must be kept in mind when studying leukemic patients using labeled leukocytes.

  16. Proteinase-Activated Receptor 1 (PAR1 regulates leukemic stem cell functions.

    Directory of Open Access Journals (Sweden)

    Nicole Bäumer

    Full Text Available External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

  17. Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches.

    Science.gov (United States)

    Hira, Vashendriya V V; Van Noorden, Cornelis J F; Carraway, Hetty E; Maciejewski, Jaroslaw P; Molenaar, Remco J

    2017-08-01

    Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes. Thus far, three types of HSC niches are recognized: endosteal, reticular and perivascular niches. However, we argue here that there is only one type of HSC niche, which consists of a periarteriolar compartment and a perisinusoidal compartment. In the periarteriolar compartment, hypoxia and low levels of reactive oxygen species preserve the HSC pool. In the perisinusoidal compartment, hypoxia in combination with higher levels of reactive oxygen species enables proliferation of progenitor cells and their mobilization into the circulation. Because HSC niches offer protection to LSCs against chemotherapy, we review novel therapeutic strategies to inhibit homing of LSCs in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, we list clinical trials of therapies that tackle LSCs in HSC niches to circumvent their protection against chemotherapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. CD25 targeted therapy of chemotherapy resistant leukemic stem cells using DR5 specific TRAIL peptide

    Directory of Open Access Journals (Sweden)

    Jayaprakasam Madhumathi

    2017-03-01

    Full Text Available Chemotherapy resistant leukemic stem cells (LSCs are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81.25% in AML and 100% in CML, ALL and CLL. IL2-TRAIL peptide showed cytotoxicity in relapsed patient samples and was more effective than TRAIL or IL2-TRAIL proteins. Additionally, DR5 specific IL2-TRAIL peptide was effective in targeting and killing LSCs purified from cell lines [IC50: 952 nM in HL60, 714 nM in MOLT4] and relapsed patient blood samples with higher efficacy (85% than IL2-TRAIL protein (46%. Hence, CD25 and DR5 specific targeting by IL2-TRAIL peptide may be an effective strategy for targeting drug resistant leukemic cells and LSCs.

  19. Radiobiological heterogeneity of leukemic lymphocyte precursors from acute lymphoblastic leukemia patients

    International Nuclear Information System (INIS)

    Uckun, F.M.; Kim, T.H.; Ramsay, N.C.; Min, W.S.; Song, C.W.

    1989-01-01

    The report outlines the authors' findings on the radiobiological features of leukemic lymphocyte precursors from acute lymphoblastic leukemia (ALL) patients. A marked heterogeneity existed between different cell lines, with a remarkable radioresistance and repair capacity in some ALL patients and an acute radiosensitivity in the absence of a detectable repair capacity in others. (U.K.)

  20. Clonal evolution of pre-leukemic hematopoietic stem cells precedes human acute myeloid leukemia.

    Science.gov (United States)

    Majeti, Ravindra

    2014-01-01

    Massively parallel DNA sequencing has uncovered recurrent mutations in many human cancers. In acute myeloid leukemia (AML), cancer genome/exome resequencing has identified numerous recurrently mutated genes with an average of 5 mutations in each case of de novo AML. In order for these multiple mutations to accumulate in a single lineage of cells, they are serially acquired in clones of self-renewing hematopoietic stem cells (HSC), termed pre-leukemic HSC. Isolation and characterization of pre-leukemic HSC have shown that their mutations are enriched in genes involved in regulating DNA methylation, chromatin modifications, and the cohesin complex. On the other hand, genes involved in regulating activated signaling are generally absent. Pre-leukemic HSC have been found to persist in clinical remission and may ultimately give rise to relapsed disease through the acquisition of novel mutations. Thus, pre-leukemic HSC may constitute a key cellular reservoir that must be eradicated for long-term cures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches

    NARCIS (Netherlands)

    Hira, Vashendriya V. V.; van Noorden, Cornelis J. F.; Carraway, Hetty E.; Maciejewski, Jaroslaw P.; Molenaar, Remco J.

    2017-01-01

    Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are

  2. Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

    Science.gov (United States)

    Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

    2014-01-01

    External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

  3. DOE to accept bids for Elk Hills crude

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that the Department of Energy will accept bids in a reoffering sale covering 53,400 b/d of Elk Hills field oil but later may exercise an option to cut sales volumes and ship 20,000 b/d to Strategic Petroleum Reserve sites in Texas. DOE rejected all 19 bids submitted in an earlier semiannual sale of crude oil from the California naval petroleum reserve, saying they were too low. DOE the, The unique combination of federal and state government policies affecting the movement of oil into and out of the California market has contributed to a situation in which it apparently is very difficult for the government to receive a price for Elk Hills oil that satisfies the minimum price tests that govern the sale of Elk Hills oil. The 12 winning bids in the reoffering sale averaged $13.58/bbl, with bids for the higher quality Stevens zone crude averaging $13.92/bbl, about 67 cents/bbl higher than bids rejected last month. DOE the 20,000 b/d is all local pipelines can ship to the interstate All-American pipeline for transfer to Texas beginning in June

  4. Rationality, irrationality and escalating behavior in lowest unique bid auctions.

    Science.gov (United States)

    Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A N

    2012-01-01

    Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

  5. Rationality, irrationality and escalating behavior in lowest unique bid auctions.

    Directory of Open Access Journals (Sweden)

    Filippo Radicchi

    Full Text Available Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

  6. Optimal bidding strategies for competitive generators and large consumers

    International Nuclear Information System (INIS)

    Fushuan Wen; David, A.K.

    2001-01-01

    There exists the potential for gaming such as strategic bidding by participants (power suppliers and large consumers) in a deregulated power market, which is more an oligopoly than a laissez-faire market. Each participant can increase his or her own profit through strategic bidding but this has a negative effect on maximising social welfare. A method to build bidding strategies for both power suppliers and large consumers in a poolco-type electricity market is presented in this paper. It is assumed that each supplier/large consumer bids a linear supply/demand function, and the system is dispatched to maximise social welfare. Each supplier/large consumer chooses the coefficients in the linear supply/demand function to maximise benefits, subject to expectations about how rival participants will bid. The problem is formulated as a stochastic optimisation problem, and solved by a Monte Carlo approach. A numerical example with six suppliers and two large consumers serves to illustrate the essential features of the method. (author)

  7. BID links ferroptosis to mitochondrial cell death pathways

    Directory of Open Access Journals (Sweden)

    Sandra Neitemeier

    2017-08-01

    Full Text Available Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the Xc- system or inhibition of glutathione peroxidase 4 (Gpx4 to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation.In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by Xc- inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Keywords: Ferroptosis, BID, Mitochondria, CRISPR, Oxytosis, Neuronal death

  8. Rationality, Irrationality and Escalating Behavior in Lowest Unique Bid Auctions

    Science.gov (United States)

    Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A. N.

    2012-01-01

    Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions – lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of “bid space”. The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets. PMID:22279553

  9. Issues in bidding for contracts for occupational therapy services.

    Science.gov (United States)

    Harms, S; Law, M

    2001-06-01

    There is an increasing number of occupational therapists in Canada who are involved in bidding for contracts to deliver occupational therapy services. Occupational therapists working in an institutional or community-based setting may not have had the responsibility of developing a proposal or a marketing plan for bidding purposes. However, the responsibility of developing a bid to compete for a service delivery contract often rests on occupational therapists who are sole practitioners in a private practice setting. The purpose of this paper is to highlight issues in the literature such as service delivery plans, marketing strategies and costing of services that can assist the occupational therapist in the development of a contractual bid. A specific clinical example, school therapy services, has been used to illustrate how these strategies can be applied to practice. Success in contractual bids appears to be primarily influenced by cost of the service, the expertise of the service provider, ability to provide coordinated care, ease of access for clients, and inclusion of methods to measure client outcome.

  10. In vitro gamma irradiation Medical Center of leukemic cells in mice, rats, and guinea pigs

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.; Ehrenreich, T.; Feldman, D.; Limbert, L.M.

    1980-01-01

    In vitro gamma irradiation of virus-induced (Gross) mouse leukemia cells at doses of 350 to 1600 rads (1 rad = 0.01 gray) had no effect on their ability to induce leukemia, usually within 2 weeks, after transplantation into syngeneic mice. However, when cells irradiated at doses of 2000-20,000 rads were transplanted, they induced leukemia after a latency period exceeding 2.5 months, similar to the results observed in mice inoculated with filtered mouse leukemia extracts. Similar results were also obtained after irradiation of leukemic cells derived from rats in which leukemia had been induced by rat-adapted mouse leukemia virus. Apparently, gamma irradiation at a dose of, or exceeding, 2000 rads, inhibits the ability of mouse and rat leukemic cells to induce leukemia after transplantation into syngeneic hosts; however, it does not inactivate the virus carried by such cells nor prevent it from inducing leukemia. [In previous experiments, doses of more than 4,500,000 rads were needed to inactivate the passage A (Gross) leukemia virus carried in either mouse or rat leukemic cells.] In vitro gamma irradiation of L2C guinea pig leukemic cells at doses of 750 to 2500 rads had no apparent effect on their ability to induce leukemia after transplantation into strain 2 guinea pigs. However, irradiation at doses of 3250 to 20,000 rads inactivated their ability to do so. The morphology of mouse, rat, and guinea pig leukemic cells and the virus particles present in such cells was not affected by irradiation at doses of 20,000 rads

  11. Quantitative assay for the number of leukemic spleen colony forming unit in radiation-induced murine myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Nara, N [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Bessho, M

    1981-11-01

    In mice with myelogenous leukemia, leukemic spleen colony forming units were assayed quantitatively. When 5 x 10/sup 3/ - 2 x 10/sup 4/ leukemic cells were transplanted to other mice of the same strain, a rectilinear relationship (p < 0.01) was found between the number of the cells transplanted and that of the colonies formed on the surface of the spleen. From these results, the authors considered that myelogenous leukemia in mice is an adequate model for acute myelogenous leukemia in human adults, and that the quantitative assay of the leukemic colony forming units can be used for sensitivity tests of antileukemic agents.

  12. Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche.

    Science.gov (United States)

    Vanegas, Natalia-Del Pilar; Vernot, Jean-Paul

    2017-01-01

    Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student's t test or the nonparametric test Kolmogorov-Smirnov. By co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone-lysine N -methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic

  13. Competitive bidding for OCS leases and environmental risk

    International Nuclear Information System (INIS)

    Englin, J.E.; Klan, M.S.

    1990-01-01

    In the last few years, the role of environment has become increasingly contentious in the process of competitive bidding for exploration and development rights of offshore petroleum leases in the outer continental shelf (OCS). Although an extensive literature exists on OCS leasing per se, relatively little work focuses on the role of environmental factors. This paper examines the effect on environmental risk on the number of firms (or joint ventures) entering bids for a given tract, which relates to the effective competition for the tracts. The next section outlines a theoretical model of bidding behavior under environmental risk. The third section presents the data used to estimate the model. The fourth section gives empirical results of an analysis of Sale No. 42, conducted in 1979 for Georges Bank in the North Atlantic. The last section provides concluding remarks

  14. Co-operative bidding of SMEs in health care sector.

    Science.gov (United States)

    Mezgár, István; Kovács, György; Bonfatti, Fabio

    2002-01-01

    Tendering become an important process for customers in the health care sector to select products and services from the market for the lowest price, with the highest quality and with the shortest delivery time. The number of SMEs (Small and Medium-sized Enterprises) delivering products or services for the health care sector is increasing, but they have usually limited capital and expertise to participate in tenders. The paper introduces a possible solution for this problem, when SMEs form special groups, so called Smart Bidding Organisations (SBO), to prepare a bid for the tender jointly. The SBO appears for the customer (tender issuer) as a single enterprise and the bidding procedure will be faster and less expensive in this way.

  15. Technical evaluation of bids for nuclear power stations

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1976-01-01

    A bid evaluation method is described which, it is claimed, facilitates a distinct and objective judgement of bids, taking into account the importance of the components, systems, and technical aspects evaluated with regard to the operation and safety of a nuclear power station. The evaluation basically consists of a cost assessment of the scope of supply deviations and a numerical evaluation of the technical design, the latter being a particularly novel feature of the method. The logic applied in both processes is shown. Main evaluation criteria which are applied for most components and systems are given as reliability, function and performance, safety, operation and maintenance, and materials. The judgements given to these evaluation criteria form the basis of the numerical bid evaluation described, which is carried out with the aid of computer programs. (U.K.)

  16. Applications of Classifying Bidding Strategies for the CAT Tournament

    Science.gov (United States)

    Gruman, Mark L.; Narayana, Manjunath

    In the CAT Tournament, specialists facilitate transactions between buyers and sellers with the intention of maximizing profit from commission and other fees. Each specialist must find a well-balanced strategy that allows it to entice buyers and sellers to trade in its market while also retaining the buyers and sellers that are currently subscribed to it. Classification techniques can be used to determine the distribution of bidding strategies used by all traders subscribed to a particular specialist. Our experiments showed that Hidden Markov Model classification yielded the best results. The distribution of strategies, along with other competition-related factors, can be used to determine the optimal action in any given game state. Experimental data shows that the GD and ZIP bidding strategies are more volatile than the RE and ZIC strategies. An MDP framework for determining optimal actions given an accurate distribution of bidding strategies is proposed as a motivator for future work.

  17. Study on Comparison of Bidding and Pricing Behavior Distinction between Estimate Methods

    Science.gov (United States)

    Morimoto, Emi; Namerikawa, Susumu

    The most characteristic trend on bidding and pricing behavior distinction in recent years is the increasing number of bidders just above the criteria for low-price bidding investigations. The contractor's markup is the difference between the bidding price and the execution price. Therefore, the contractor's markup is the difference between criteria for low-price bidding investigations price and the execution price in the public works bid in Japan. Virtually, bidder's strategies and behavior have been controlled by public engineer's budgets. Estimation and bid are inseparably linked in the Japanese public works procurement system. The trial of the unit price-type estimation method begins in 2004. On another front, accumulated estimation method is one of the general methods in public works. So, there are two types of standard estimation methods in Japan. In this study, we did a statistical analysis on the bid information of civil engineering works for the Ministry of Land, Infrastructure, and Transportation in 2008. It presents several issues that bidding and pricing behavior is related to an estimation method (several estimation methods) for public works bid in Japan. The two types of standard estimation methods produce different results that number of bidders (decide on bid-no bid strategy) and distribution of bid price (decide on mark-up strategy).The comparison on the distribution of bid prices showed that the percentage of the bid concentrated on the criteria for low-price bidding investigations have had a tendency to get higher in the large-sized public works by the unit price-type estimation method, comparing with the accumulated estimation method. On one hand, the number of bidders who bids for public works estimated unit-price tends to increase significantly Public works estimated unit-price is likely to have been one of the factors for the construction companies to decide if they participate in the biddings.

  18. Bid process and contracting for remediation in New Mexico

    International Nuclear Information System (INIS)

    Fox, K.

    1994-01-01

    In an effort to provide cost effective and timely reclamation services to high priority leaking underground storage tank sites the New Mexico Environment Department has implemented a reclamation bidding process for qualified state contractors. The bid process was implemented in an attempt to make reclamation contractors more competitive and to encourage innovative technologies and contracting mechanisms. Overall the Bureau has received positive feedback from contractors participating in the process, especially regarding innovative technology and contracting. In addition, the process has provided excellent training for project managers and has allowed a critical review of the reclamation process for UST sites in general

  19. Models for electricity market efficiency and bidding strategy analysis

    Science.gov (United States)

    Niu, Hui

    This dissertation studies models for the analysis of market efficiency and bidding behaviors of market participants in electricity markets. Simulation models are developed to estimate how transmission and operational constraints affect the competitive benchmark and market prices based on submitted bids. This research contributes to the literature in three aspects. First, transmission and operational constraints, which have been neglected in most empirical literature, are considered in the competitive benchmark estimation model. Second, the effects of operational and transmission constraints on market prices are estimated through two models based on the submitted bids of market participants. Third, these models are applied to analyze the efficiency of the Electric Reliability Council Of Texas (ERCOT) real-time energy market by simulating its operations for the time period from January 2002 to April 2003. The characteristics and available information for the ERCOT market are considered. In electricity markets, electric firms compete through both spot market bidding and bilateral contract trading. A linear asymmetric supply function equilibrium (SFE) model with transmission constraints is proposed in this dissertation to analyze the bidding strategies with forward contracts. The research contributes to the literature in several aspects. First, we combine forward contracts, transmission constraints, and multi-period strategy (an obligation for firms to bid consistently over an extended time horizon such as a day or an hour) into the linear asymmetric supply function equilibrium framework. As an ex-ante model, it can provide qualitative insights into firms' behaviors. Second, the bidding strategies related to Transmission Congestion Rights (TCRs) are discussed by interpreting TCRs as linear combination of forwards. Third, the model is a general one in the sense that there is no limitation on the number of firms and scale of the transmission network, which can have

  20. 48 CFR 614.402-70 - Waiver of public opening of bids.

    Science.gov (United States)

    2010-10-01

    ... of public opening of bids. Overseas posts may request waiver of the public opening of bids if that activity is inconsistent with local law or legal practice, or with post security. For that purpose, the...

  1. Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

    Directory of Open Access Journals (Sweden)

    Diana Bayer

    2012-04-01

    Full Text Available Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl-diphenyltetrazolium bromide assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes.Functional Foods in Health and Disease 2012, 2(4:72-85 Conclusions: The three tea extracts studied altered leukemic T lymphocyte

  2. Bidding Strategies in Agent-based Continuous Double Auctions

    NARCIS (Netherlands)

    H. Ma (Huiye); H.-F. Leung

    2008-01-01

    htmlabstractOnline auctions are a platform to trade goods on the Internet. In this context, negotiation capabilities for software agents in continuous double auctions (CDAs) are a central concern. Agents need to be able to prepare bids for and evaluate offers on behalf of the users they represent

  3. Supply curve bidding of electricity in constrained power networks

    International Nuclear Information System (INIS)

    Al-Agtash, Salem Y.

    2010-01-01

    This paper presents a Supply Curve Bidding (SCB) approach that complies with the notion of the Standard Market Design (SMD) in electricity markets. The approach considers the demand-side option and Locational Marginal Pricing (LMP) clearing. It iteratively alters Supply Function Equilibria (SFE) model solutions, then choosing the best bid based on market-clearing LMP and network conditions. It has been argued that SCB better benefits suppliers compared to fixed quantity-price bids. It provides more flexibility and better opportunity to achieving profitable outcomes over a range of demands. In addition, SCB fits two important criteria: simplifies evaluating electricity derivatives and captures smooth marginal cost characteristics that reflect actual production costs. The simultaneous inclusion of physical unit constraints and transmission security constraints will assure a feasible solution. An IEEE 24-bus system is used to illustrate perturbations of SCB in constrained power networks within the framework of SDM. By searching in the neighborhood of SFE model solutions, suppliers can obtain their best bid offers based on market-clearing LMP and network conditions. In this case, electricity producers can derive their best offering strategy both in the power exchange and the long-term contractual markets within a profitable, yet secure, electricity market. (author)

  4. Application of fuzzy mathematics in assessment of mine design bidding

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Sen

    1988-12-01

    Assessment of mine design bidding is mainly to evaluate the quality of a mine design. The paper established a 3-stage model to assess quality of mine design using fuzzy criterion. A concept of assessment figures was proposed in the analysis of the results. Finally, a mine design was assessed. 2 refs., 2 figs., 1 tab.

  5. Sealed bid auctions with ambiguity: theory and experiments

    Czech Academy of Sciences Publication Activity Database

    Chen, Y.; Katuščák, Peter; Ozdenoren, E.

    2007-01-01

    Roč. 136, č. 1 (2007), s. 513-535 ISSN 0022-0531 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : sealed bid auctions * ambiguity * experiment Subject RIV: AH - Economics Impact factor: 1.353, year: 2007

  6. Sealed bid auctions with ambiguity: an experimental study

    Czech Academy of Sciences Publication Activity Database

    Chen, Y.; Katuščák, Peter; Ozdenoren, E.

    -, č. 269 (2005), s. 1-75 ISSN 1211-3298 Institutional research plan: CEZ:AV0Z70850503 Keywords : sealed bid auctions * ambiguity * experiment Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp269.pdf

  7. Sealed-Bid Auction of Dutch Mussels : Statistical Analysis

    NARCIS (Netherlands)

    Kleijnen, J.P.C.; van Schaik, F.D.J.

    2007-01-01

    This article presents an econometric analysis of the many data on the sealed-bid auction that sells mussels in Yerseke town, the Netherlands. The goals of this analy- sis are obtaining insight into the important factors that determine the price of these mussels, and quantifying the performance of an

  8. Sealed-bid auction of Netherlands mussels: statistical analysis

    NARCIS (Netherlands)

    Kleijnen, J.P.C.; van Schaik, F.D.J.

    2011-01-01

    This article presents an econometric analysis of the many data on the sealed-bid auction that sells mussels in Yerseke town, the Netherlands. The goals of this analysis are obtaining insight into the important factors that determine the price of these mussels, and quantifying the performance of an

  9. Supply curve bidding of electricity in constrained power networks

    Energy Technology Data Exchange (ETDEWEB)

    Al-Agtash, Salem Y. [Hijjawi Faculty of Engineering; Yarmouk University; Irbid 21163 (Jordan)

    2010-07-15

    This paper presents a Supply Curve Bidding (SCB) approach that complies with the notion of the Standard Market Design (SMD) in electricity markets. The approach considers the demand-side option and Locational Marginal Pricing (LMP) clearing. It iteratively alters Supply Function Equilibria (SFE) model solutions, then choosing the best bid based on market-clearing LMP and network conditions. It has been argued that SCB better benefits suppliers compared to fixed quantity-price bids. It provides more flexibility and better opportunity to achieving profitable outcomes over a range of demands. In addition, SCB fits two important criteria: simplifies evaluating electricity derivatives and captures smooth marginal cost characteristics that reflect actual production costs. The simultaneous inclusion of physical unit constraints and transmission security constraints will assure a feasible solution. An IEEE 24-bus system is used to illustrate perturbations of SCB in constrained power networks within the framework of SDM. By searching in the neighborhood of SFE model solutions, suppliers can obtain their best bid offers based on market-clearing LMP and network conditions. In this case, electricity producers can derive their best offering strategy both in the power exchange and the long-term contractual markets within a profitable, yet secure, electricity market. (author)

  10. 48 CFR 252.247-7008 - Evaluation of bids.

    Science.gov (United States)

    2010-10-01

    ... other factors, the Contracting Officer will evaluate bids on the basis of advantages or disadvantages to... evaluation, the Contracting Officer will assume that the administrative cost to the Government for issuing... Government, including the administrative costs in paragraph (b)(1). (c) When drayage is necessary for the...

  11. 48 CFR 811.104-74 - Bid evaluation and award.

    Science.gov (United States)

    2010-10-01

    ... COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents... offered products are clearly identified in the bid and are equal in all material respects to the products... brand name and make or model number, descriptive material, and any modifications of brand name products...

  12. Integrated Bidding and Operating Strategies for Wind-Storage Systems

    DEFF Research Database (Denmark)

    Ding, Huajie; Pinson, Pierre; Hu, Zechun

    2016-01-01

    Due to their flexible charging and discharging capabilities, energy storage systems (ESS) are considered a promising complement to wind farms (WFs) participating in electricity markets. This paper presents integrated day-ahead bidding and real-time operation strategies for a wind-storage system...

  13. 47 CFR 54.603 - Competitive bid requirements.

    Science.gov (United States)

    2010-10-01

    ... requester cannot obtain toll-free access to an Internet service provider; (iv) The requested service or... be sold, resold or transferred in consideration of money or any other thing of value; and (vi) If the.... (a) Competitive bidding requirement. To select the telecommunications carriers that will provide...

  14. Optimal generator bidding strategies for power and ancillary services

    Science.gov (United States)

    Morinec, Allen G.

    As the electric power industry transitions to a deregulated market, power transactions are made upon price rather than cost. Generator companies are interested in maximizing their profits rather than overall system efficiency. A method to equitably compensate generation providers for real power, and ancillary services such as reactive power and spinning reserve, will ensure a competitive market with an adequate number of suppliers. Optimizing the generation product mix during bidding is necessary to maximize a generator company's profits. The objective of this research work is to determine and formulate appropriate optimal bidding strategies for a generation company in both the energy and ancillary services markets. These strategies should incorporate the capability curves of their generators as constraints to define the optimal product mix and price offered in the day-ahead and real time spot markets. In order to achieve such a goal, a two-player model was composed to simulate market auctions for power generation. A dynamic game methodology was developed to identify Nash Equilibria and Mixed-Strategy Nash Equilibria solutions as optimal generation bidding strategies for two-player non-cooperative variable-sum matrix games with incomplete information. These games integrated the generation product mix of real power, reactive power, and spinning reserve with the generators's capability curves as constraints. The research includes simulations of market auctions, where strategies were tested for generators with different unit constraints, costs, types of competitors, strategies, and demand levels. Studies on the capability of large hydrogen cooled synchronous generators were utilized to derive useful equations that define the exact shape of the capability curve from the intersections of the arcs defined by the centers and radial vectors of the rotor, stator, and steady-state stability limits. The available reactive reserve and spinning reserve were calculated given a

  15. Procurement of construction services: a case study on bidding competition in Singapore public sector contracts

    Science.gov (United States)

    Oo, B. L.; Yan, Y.

    2018-04-01

    There are many variables that public clients need to consider in their bidding procedure to enhance efficiency in their procurement for construction services. This paper focusses on the competitive bidding process for public sector procurement of construction services in Singapore. A distinctive feature of the Singapore government competitive bidding process is that full bidding feedback information is released to all competing bidders (and public). The specific objectives are: (i) to examine the degree of competition in the construction markets; and (ii) to examine the bidding performance of competing bidders. Based on a collection of bidding data for a 15-month period, the results show the market environment of the Singapore public sector construction contracting is highly competitive with long bidder lists. In selection of contractors, only 50% of the contracts were awarded to lowest bidders. The results also show that the competing contractors can be broadly classified into three groups based on their bidding performance in terms of number of bidding attempts, bidding success rate and bidding competitiveness. These results provide a useful insight into the bidding competition in the Singapore public sector construction contracting, especially to new market entrants and foreign contractors who want to bid for jobs in Singapore.

  16. Elicited Bid Functions in a (a)Symmetric First-Price Auctions

    NARCIS (Netherlands)

    Pezanis-Christou, P.; Sadrieh, A.

    2003-01-01

    We report on a series of experiments that examine bidding behavior in first-price sealed bid auctions with symmetric and asymmetric bidders.To study the extent of strategic behavior, we use an experimental design that elicits bidders complete bid functions in each round (auction) of the

  17. 42 CFR 422.256 - Review, negotiation, and approval of bids.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Review, negotiation, and approval of bids. 422.256... Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a) Authority. Subject to... submitted under § 422.252 and conduct negotiations with MA organizations regarding these bids (including the...

  18. 47 CFR 1.2105 - Bidding application and certification procedures; prohibition of certain communications.

    Science.gov (United States)

    2010-10-01

    ....2110, a statement to that effect and a declaration, under penalty of perjury, that the applicant is... the post-auction market structure. (ix) Certification under penalty of perjury that it has not entered... amount of their bids, bidding strategies or the particular licenses on which they will or will not bid...

  19. 30 CFR 260.111 - What conditions apply to the bidding systems that MMS uses?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What conditions apply to the bidding systems that MMS uses? 260.111 Section 260.111 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE... What conditions apply to the bidding systems that MMS uses? (a) For each of the bidding systems in...

  20. 42 CFR 423.265 - Submission of bids and related information.

    Science.gov (United States)

    2010-10-01

    ... guidelines based on generally accepted actuarial principles. A qualified actuary must certify the plan's... member of the American Academy of Actuaries to be deemed qualified. Applicants may use qualified outside actuaries to prepare their bids. (d) Specific requirements for bids. The bid and supplemental information...

  1. 76 FR 20571 - Bidding by Affiliates in Open Seasons for Pipeline Capacity

    Science.gov (United States)

    2011-04-13

    ... bidding is inappropriate and, therefore, prohibited. \\9\\ Tenaska Marketing Ventures, et al., 126 FERC ] 61... multiple affiliates at a competitive disadvantage. In theory, a company could employ this strategy to the... submitting their bids. For example, a marketing arm of an energy company may bid to secure capacity for its...

  2. Game Theory Analysis of Bidding for A Construction Contract

    Science.gov (United States)

    Kembłowski, Marian W.; Grzyl, Beata; Siemaszko, Agata

    2017-10-01

    The authors are concerned with a bidding problem. There are two companies (P1 and P2) bidding for a highway construction project. In order to be more competitive, P1 considers buying a new gravel pit near the construction site. The basic cost of the pit is known to both companies. However, there is also an additional, hidden, cost (C) known only to P1. P2 is uncertain whether the hidden cost is C = 0 or C = x. P1 plans to bid for the job, but has to decide whether to buy the gravel pit. P2, not having a complete knowledge about C, thus not knowing the strategy choice of P1, has to decide if to bid for the job. In effect we have two payoff matrices, one for the additional cost C = 0, and the other one for C = x. If the probability of P2 bidding for the project can be estimated by propagating intelligence information through a Bayesian Belief Network, the best strategy for P1 can be readily determined. Otherwise, the solution calls for changing this game of incomplete information (players may or may not know some information about the other players, e.g., their “type,” their strategies, payoffs) into a game of imperfect information (players are simply unaware of the actions chosen by other players). This is achieved by introducing an additional “Nature” node which for this problem determines with some probability “p” the additional cost C= 0 (thus, C = x with probability 1-p). The solution of this game turns out to depend on the probability “p”. For some values of p the game is solved with pure strategies, whereas for other values the game is in equilibrium when the players randomly mix their strategies.

  3. Studies by radioiodination of normal adult, fetal and leukemic cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kannourakis, G; Cauchi, M N [Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia

    1978-01-01

    A comparison was made between cord blood lymphocytes, normal adult lymphocytes and leukemic cells after membrane iodination with lactoperoxidase. A double-labeling technique using lactoperoxidase iodination with /sup 125/I and /sup 131/I followed by analysis on polyacrylamide gel electrophoresis revealed a number of membrane differences between leukemic, normal and fetal cells. There was a reduction in the 70,000 molecular weight component in cord blood cells compared to adult lymphocytes, and an increase in membrane peptides with molecular weights of 35,000, 20,000, 9,000 and 4,000. Although smaller molecular weight peptides were also present in chronic lymphatic leukemia as well as acute myeloid leukemia, these were shown to be distinct from fetal type membrane components.

  4. Uncontrolled hypertension secondary to leukemic cell infiltration of kidneys in a hemodialysis patient

    Directory of Open Access Journals (Sweden)

    Kultigin Turkmen

    2010-06-01

    Full Text Available Kultigin Turkmen1, Lutfullah Altintepe2, Ibrahim Guney2, Ismet Aydogdu3, Osman Koc4, Mehmet Ali Erkut5, Halil Zeki Tonbul11Department of Nephrology, Meram School of Medicine, Selcuk University, 2Meram Training and Research Hospital, Selcuk University, 3Department of Hematology, Meram School of Medicine, Selcuk University, 4Department of Radiology, Meram School of Medicine, Selcuk University, 5Department of Hematology, Meram Training and Research Hospital, Selcuk UniversityAbstract: Leukemic infiltration of the kidney is usually silent, and the admission of the patients with renal dysfunction or acute kidney injury is uncommon. We present a 34-year old hemodialysis patient with new onset of uncontrolled hypertension, erythropoietin-resistant anemia, thrombocytopenia, and Bell’s palsy. On admission, his blood pressure (BP was 210/110 mmHg and he had petechiae and purpura at upper and lower extremities. Renal ultrasonography (USG showed bilaterally enlarged kidneys without hydronephrosis, unlike his previous USG, which determined bilaterally atrophic kidneys. Acute lymphoblastic leukemia, hypertensive crisis due to bilateral leukemic cell infiltration of kidneys, tumor lysis syndrome, and leukemic involvement of the facial nerve were diagnosed. Despite intense antihypertensive management, his BP was not controlled. After prednisolone, daunorubicine, and vincristine therapy, the size of kidneys diminished and his BP dropped under normal range. In conclusion, pathological findings such as uncontrolled hypertension, flank pain, skin rashes, and abnormal blood count should be considered carefully, even in patients with end-stage renal disease receiving renal replacement therapy.Keywords: leukemic cell infiltration, uncontrolled hypertension, hemodialysis

  5. Leukemic meningitis in a patient with hairy cell leukemia. A case report

    International Nuclear Information System (INIS)

    Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

    1984-01-01

    Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms

  6. NKp46 identifies an NKT cell subset susceptible to leukemic transformation in mouse and human

    Science.gov (United States)

    Yu, Jianhua; Mitsui, Takeki; Wei, Min; Mao, Hsiaoyin; Butchar, Jonathan P.; Shah, Mithun Vinod; Zhang, Jianying; Mishra, Anjali; Alvarez-Breckenridge, Christopher; Liu, Xingluo; Liu, Shujun; Yokohama, Akihiko; Trotta, Rossana; Marcucci, Guido; Benson, Don M.; Loughran, Thomas P.; Tridandapani, Susheela; Caligiuri, Michael A.

    2011-01-01

    IL-15 may have a role in the development of T cell large granular lymphocyte (T-LGL) or NKT leukemias. However, the mechanisms of action and the identity of the cell subset that undergoes leukemic transformation remain elusive. Here we show that in both mice and humans, NKp46 expression marks a minute population of WT NKT cells with higher activity and potency to become leukemic. Virtually 100% of T-LGL leukemias in IL-15 transgenic mice expressed NKp46, as did a majority of human T-LGL leukemias. The minute NKp46+ NKT population, but not the NKp46– NKT population, was selectively expanded by overexpression of endogenous IL-15. Importantly, IL-15 transgenic NKp46– NKT cells did not become NKp46+ in vivo, suggesting that NKp46+ T-LGL leukemia cells were the malignant counterpart of the minute WT NKp46+ NKT population. Mechanistically, NKp46+ NKT cells possessed higher responsiveness to IL-15 in vitro and in vivo compared with that of their NKp46– NKT counterparts. Furthermore, interruption of IL-15 signaling using a neutralizing antibody could prevent LGL leukemia in IL-15 transgenic mice. Collectively, our data demonstrate that NKp46 identifies a functionally distinct NKT subset in mice and humans that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. Thus, IL-15 signaling and NKp46 may be useful targets in the treatment of patients with T-LGL or NKT leukemia. PMID:21364281

  7. Correlation of total body potassium and leukemic cell mass in patients with chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Chandra, P.; Sawitsky, A.; Chanana, A.D.; Chikkappa, G.; Cohn, S.H.; Rai, K.R.; Cronkity, E.P.

    1979-01-01

    Total body leukemic mass in patients with chronic lymphocytic leukemia (CLL) was measured by quantitation of total body potassium (TBK) with a whole-body counter. In addition, the predicted normal total body potassium (Kp) for each patient was calculated from an empirically derived relationship involving height, weight age, and sex. Both the absolute TBK and the relative excess of total body potassium (TBK/Kp) were related to the stage of disease. Patients in the early stages of CLL were found to have lower TBK and TBK/Kp than patients in the late stages of disease. Both of these parameters increased with the successively advanced stages of the disease. The clinically monitored reduction of leukemic cell mass following therapy was accompanied by reductions in TBK and TBK/Kp. Data presented support the notion that TBK/Kp is a useful indicator of the total body leukemic mass. Futhermore, the results of these studies quantitatively validate the proposed clinical staging system for CLL. Quantitation of TBK by a whole-body counter is an accurate and noninvasive procedure and does not require administration of isotopes

  8. Synergistic apoptosis induction in leukemic cells by the phosphatase inhibitor salubrinal and proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Hannes C A Drexler

    Full Text Available Cells adapt to endoplasmic reticulum (ER-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD, however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1

  9. The impact of competitive bidding on the market prospects for renewable electric technologies

    Energy Technology Data Exchange (ETDEWEB)

    Swezey, B G

    1993-09-01

    This report examines issues regarding the ability of renewable-energy-based generation projects to compete fossil-fuel-based projects in competitive bidding solicitations. State and utility bidding results revealed that on a relative basis, utilities contract for less renewable-energy-based capacity under competitive bidding than under past methods of qualifying facility contracting. It was concluded that renewables are not being chosen more often under competitive bidding because it emphasizes price and operating considerations over other attributes of renewables, such as environmental considerations, fuel diversity, and fuel price stability. Examples are given of bidding approaches used by some states and utilities that have resulted in renewables-based projects winning generation bids. In addition, the appendix summarizes, by state, competitive bidding activities and results for supply-side solicitations that were open to all fuels and technologies.

  10. 78 FR 59055 - Notice of Realty Action: Modified Competitive Sealed-Bid Sale of Public Land at Schoolhouse Butte...

    Science.gov (United States)

    2013-09-25

    ..., offering designated bidders the right to meet the highest valid bid. Refusal or failure to meet the highest... checks will not be accepted. Sealed bid envelopes must be clearly marked on the lower left corner with ``SEALED BID BLM LAND SALE'' and the identification number ``BLM SERIAL NUMBER N-85116.'' The bid envelope...

  11. Pay-as-bid based reactive power market

    International Nuclear Information System (INIS)

    Amjady, N.; Rabiee, A.; Shayanfar, H.A.

    2010-01-01

    In energy market clearing, the offers are stacked in increasing order and the offer that intersects demand curve, determines the market clearing price (MCP). In reactive power market, the location of reactive power compensator is so important. A low cost reactive producer may not essentially be favorable if it is far from the consumer. Likewise, a high cost local reactive compensator at a heavily loaded demand center of network could be inevitably an alternative required to produce reactive power to maintain the integrity of power system. Given the background, this paper presents a day-ahead reactive power market based on pay-as-bid (PAB) mechanism. Generators expected payment function (EPF) is used to construct a bidding framework. Then, total payment function (TPF) of generators is used as the objective function of optimal power flow (OPF) problem to clear the PAB based market. The CIGRE-32 bus test system is used to examine the effectiveness of the proposed reactive power market.

  12. Process Document for the Conservation Competitive Bidding Pilot Program.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1990-09-01

    Bonneville Power Administration (Bonneville) is proposing to test competitive bidding for Conservation Resources to expand its existing resource acquisition capabilities. Competitive bidding may target specific types of electric end-uses or end-use sectors. It is a new acquisition approach through which Bonneville seeks to acquire resources that are not acquired through other existing or planned conservation programs. This proposal describes the conservation component of the all-source competitive acquisition approach that will be developed. It is expected that the combined resource acquisition effort will target about 100 average megawatts (aMW) as proposed in the 1990 Resource Program, although the exact amount has not yet been determined. Increasing the acquisition target will, to some extent, depend on whether the proposed pilot program is large enough to establish confidence in the approach.

  13. Pay-as-bid based reactive power market

    Energy Technology Data Exchange (ETDEWEB)

    Amjady, N. [Department of Electrical Engineering, Semnan University, Semnan (Iran, Islamic Republic of); Rabiee, A., E-mail: Rabiee@iust.ac.i [Center of Excellence for Power System Automation and Operation, Department of Electrical Engineering, Iran University of Science and Technology, Tehran (Iran, Islamic Republic of); Shayanfar, H.A. [Center of Excellence for Power System Automation and Operation, Department of Electrical Engineering, Iran University of Science and Technology, Tehran (Iran, Islamic Republic of)

    2010-02-15

    In energy market clearing, the offers are stacked in increasing order and the offer that intersects demand curve, determines the market clearing price (MCP). In reactive power market, the location of reactive power compensator is so important. A low cost reactive producer may not essentially be favorable if it is far from the consumer. Likewise, a high cost local reactive compensator at a heavily loaded demand center of network could be inevitably an alternative required to produce reactive power to maintain the integrity of power system. Given the background, this paper presents a day-ahead reactive power market based on pay-as-bid (PAB) mechanism. Generators expected payment function (EPF) is used to construct a bidding framework. Then, total payment function (TPF) of generators is used as the objective function of optimal power flow (OPF) problem to clear the PAB based market. The CIGRE-32 bus test system is used to examine the effectiveness of the proposed reactive power market.

  14. Bid Protests on DoD Source Selections

    Science.gov (United States)

    2017-06-13

    values, Government Accountability Office 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER a. REPORT b. ABSTRACT c. THIS PAGE ABSTRACT OF...Logistics (AT&L) closely monitors the Government Accountability Office (GAO) Bid Protest statistics for trends. These statistics combined with our trend...protests, cost claims, and requests for reconsideration. This report discusses protests only. The GAO reports case types by docket numbers (B-#) where

  15. Interconnected Power Systems Mexico-Guatemala financed by BID

    International Nuclear Information System (INIS)

    Martinez, Veronica

    2003-01-01

    The article describes the plans for the interconnection of the electric power systems of Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama and Mexico within the project Plan Pueba Panama. The objective of the interconnection is to create an electric market in the region that contributes to reduce costs and prices. The project will receive a financing of $37.5 millions of US dollars from the Banco Intrameramericano de Desarrollo (BID)

  16. BID links ferroptosis to mitochondrial cell death pathways.

    Science.gov (United States)

    Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

    2017-08-01

    Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the X c - system or inhibition of glutathione peroxidase 4 (Gpx4) to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation. In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by X c - inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Technical evaluation of bids for nuclear power plants

    International Nuclear Information System (INIS)

    1981-01-01

    In continuation of its efforts to provide comprehensive and impartial guidance to Member States facing the need to introduce nuclear power, the International Atomic Energy Agency is issuing this guidebook as part of a series of guidebooks and codes of practice and, in particular, as a necessary supplement to 'Economic Evaluation of Bids for Nuclear Power Plants: A Guidebook', published by the IAEA in 1976 as Technical Reports Series No.175. The present publication is intended for project managers and senior engineers of electric utilities who are concerned with the evaluation of bids for a nuclear power project. It assumes that the reader has a good knowledge of the technical characteristics of nuclear power plants and of nuclear power project implementation. Its purpose is to provide the information necessary to organize, guide and supervise the technical evaluation of bids for a nuclear power project. It goes without saying that the technical staff carrying out the evaluation must have prior technical experience which cannot be provided by a guidebook

  18. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  19. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    DEFF Research Database (Denmark)

    Obro, Nina F; Ryder, Lars P; Madsen, Hans O

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring...... clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and....../or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative...

  20. Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Huijuan; Tan, Shi; Wang, Juan; Chen, Shana; Quan, Jing; Xian, Jingrong; Zhang, Shuai shuai; He, Jingang; Zhang, Ling, E-mail: lingzhang@cqmu.edu.cn

    2014-01-01

    The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment. - Highlights: • Knockdown of Msi2 inhibited K562 cell growth and arrested cell cycle progression. • Knockdown of Msi2 induced K562 cell apoptosis via the regulation of Bax and Bcl-2. • The MAPK pathway was involved in the process of Msi2-mediated leukemogenesis. • Our data indicate that Msi2 is a potential new target for leukemia treatment.

  1. Pre leukemic granulocytic sarcoma of vagina: a case report with review of literature

    International Nuclear Information System (INIS)

    Lakshminarasimhan, Srinivasan; Doval, D.C.; Rajashekhar, Usha; Mukherjee, Geethashree; Kannan, V.; Lakshmi Devi; Bapsy, P.P.

    1996-01-01

    Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells, that may precede the onset of acute myeloid leukemia or appear during the leukemic manifestation or blastic crisis of chronic myeloproliferative disorders. A case of granulocytic sarcoma of vagina in a 27 year old woman treated with local radiotherapy is described. After seven months of follow up she developed acute myeloid leukemia. The case has been presented in view of its rarity and discussed in light of the available literature. (author). 13 refs., 1 fig

  2. Analysis of equilibrium about bidding strategy of suppliers with future contracts

    International Nuclear Information System (INIS)

    Yuan, Zhiqiang; Liu, Dong; Jiang, Chuanwen

    2007-01-01

    In this paper, the supply function model is employed to simulate the bidding strategy of suppliers in the power pool, and models of the supply function with future contracts are presented. It is proved that only one of the parameters between slope and intercept of the bidding curve is an independent variable in order to achieve definite equilibrium. In the meantime, the equilibria of the bidding strategy about suppliers are studied when different intercepts of the bidding curve are chosen. Some examples are employed to study the Nash equilibrium strategies of suppliers with different future contracts in various bidding strategy models. The results show that the equilibria are different in different bidding strategy models, but the future contracts can effectively make spot prices decrease in all the models

  3. High Bids and Low Recovery: A Possible Case for Non-Performing Loan Auctions in India

    OpenAIRE

    Pandey, Ashish

    2016-01-01

    This paper considers the possibility that the prices bid by asset reconstruction companies in India under a security receipt mechanism may not reflect the ultimate recoverable value of nonperforming loans. The paper establishes, using a model and simulations, that the price bid by asset reconstruction companies will reveal their own rational interest and can significantly exceed the recoverable value. The conclusions arrived in this paper raise concerns regarding the use of bids as an indicat...

  4. Which countries bid for the Olympic Games? Economic, political, and social factors and chances of winning

    OpenAIRE

    Maennig, Wolfgang; Vierhaus, Christopher

    2016-01-01

    This contribution analyzes 132 factors on their potential to discriminate countries bidding for hosting the Olympic Games from non-bidding countries. Our binary, clustered model using generalized estimating equations (GEE) shows that countries recording long-term economic growth and pursuing a liberalization and globalization policy will consider an Olympic bid. In addition, countries with an urban population above 10 million, with stable election results and an improvement in health standard...

  5. Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

    Science.gov (United States)

    2014-01-01

    Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

  6. A multi-space model for Chinese bids evaluation with analyzing

    OpenAIRE

    Mao, Linfan

    2006-01-01

    A tendering is a negotiating process for a contract through by a tenderer issuing an invitation, bidders submitting bidding documents and the tenderer accepting a bidding by sending out a notification of award. As a useful way of purchasing, there are many norms and rulers for it in the purchasing guides of the World Bank, the Asian Development Bank, $...$, also in contract conditions of various consultant associations. In China, there is a law and regulation system for tendering and bidding....

  7. A Robust Open Ascending-price Multi-unit Auction Protocol against False-name Bids

    Science.gov (United States)

    Iwasaki, Atsushi; Yokoo, Makoto; Terada, Kenji

    This paper develops a new ascending-price multi-unit auction protocol that has following characteristics: (i) it has an open format, (ii) sincere bidding is an equilibrium strategy even if the marginal utilities of each agent can increase and agents can submit false-name bids. False-name bids are bids submitted under fictitious names such as multiple e-mail addresses, which can be done easily in the Internet. This is the first protocol that has these two characteristics. We show that our new protocol outperforms an existing protocol, which satisfies (ii), with respect to the social surplus and the seller's revenue.

  8. Winning PEMEX consulting contracts through international bidding : sharing a Canadian success strategy

    International Nuclear Information System (INIS)

    Lin, J.

    1999-01-01

    A series of brief notes and overhead viewgraphs accompanied this presentation which described how Enbridge Technology obtained a contract with Mexico's PEMEX Refining through an international open bid. The scope of the contract was to advise PEMEX on how to modernize and automate their national liquids pipeline system. The value of the contract was US$11.6 million. The time span was from April 1998 to October 1999. A flow chart was included which illustrated the typical international bidding process. Enbridge prepared their bid by paying attention to bid basis details and emphasized their technical qualifications. 1 fig

  9. The Race for Sponsored Links: Bidding Patterns for Search Advertising

    OpenAIRE

    Zsolt Katona; Miklos Sarvary

    2010-01-01

    Paid placements on search engines reached sales of nearly $11 billion in the United States last year and represent the most rapidly growing form of online advertising today. In its classic form, a search engine sets up an auction for each search word in which competing websites bid for their sponsored links to be displayed next to the search results. We model this advertising market, focusing on two of its key characteristics: (1) the interaction between the list of search results and the lis...

  10. Metalearning to support competitive electricity market players' strategic bidding

    DEFF Research Database (Denmark)

    Pinto, Tiago; Sousa, Tiago M.; Morais, Hugo

    2016-01-01

    a dynamic artificial neural network to create its own output, taking advantage on several learning algorithms already implemented in ALBidS (Adaptive Learning strategic Bidding System). The proposed metalearner considers different weights for each strategy, based on their individual performance......Electricity markets are becoming more competitive, to some extent due to the increasing number of players that have moved from other sectors to the power industry. This is essentially resulting from incentives provided to distributed generation. Relevant changes in this domain are still occurring...

  11. Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells

    Energy Technology Data Exchange (ETDEWEB)

    Panayotides, P; Sjoegren, A -M; Reizenstein, P; Porwit, A. Immunopathology Lab., Dept. of Pathology, Karolinska Hospital, Stockholm; Wasserman, J

    1988-01-01

    Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by /sup 3/H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the /sup 51/Cr release assay. LAK cells showed a cytotoxicity (over 10% specific /sup 51/Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) /sup 51/Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.

  12. Demonstration of interleukin-1 beta transcripts in acute myeloblastic leukemic cells by in situ hybridization.

    Science.gov (United States)

    Nakamura, M; Kanakura, Y; Furukawa, Y; Ernst, T J; Griffin, J D

    1990-07-01

    The cells from some patients with acute myeloblastic leukemia will secrete autostimulatory cytokines in tissue culture without the addition of stimulators such as phorbol 12-myristate 13-acetate. Production of interleukin-1 beta (IL-1 beta), for example, has been observed in up to 50% of cases. In order to investigate the nature of the cell secreting IL-1 beta in AML, we used an antisense RNA probe to detect specific IL-1 beta transcripts in individual leukemic cells by in situ hybridization. In fresh, uncultured cells, IL-1 beta transcripts were observed in 1-40% of undifferentiated leukemic blast cells in 17 of 19 cases. In situ hybridization was at least as sensitive as Northern blot analysis in detecting IL-1 beta transcripts. No correlation of IL-1 beta transcript expression with FAB classification was observed. Normal blood and bone marrow mononuclear cells did not contain cells expressing IL-1 beta transcripts. These results support the concept that the regulation of cytokine genes in AML cells is aberrant.

  13. Altered expression of asparagine synthetase mRNA in human leukemic and carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Goodwin, L.O.; Guzowski, D.E.; Millan, C.A. [North Shore Univ. Hospital/Cornell Univ. Medical College, Manhasset, NY (United States)] [and others

    1994-09-01

    Asparagine synthetase (AS) is the enzyme responsible for the ATP-dependant conversion of aspartic acid to asparagine. The AS gene is expressed constitutively in most mammalian cells, including cells of the lymphoid lineage, as a 2 kb mRNA. In some leukemic phenotypes, AS expression is abrogated, resulting in no detectable enzyme activity. These cells are rendered sensitive to killing by L-asparaginase, which destroys extracellular asparagine. Prolonged treatment of leukemic cells with this agent can lead to resistance and the reappearance of AS activity, suggesting derepression of the AS gene, which has been shown to be regulated by intracellular levels of asparagine. Modulation of AS expression by asparagine employs cis and trans-acting elements involved in transcriptional and translational regulation. We have cloned and sequenced the human AS gene and surrounding sequence elements as well as the full-length cDNA. Using probes specific to the third and fourth exons of AS, we have identified an additional higher molecular weight mRNA (2.7 kb) in Northern blots derived from a chronic myelogenous leukemia and a colon carcinoma but not in normal lymphocytic or other human cell lines. We speculate that elements present in the cancer-derived mRNAs may be involved in the derepression of AS activity. This hypothesis is being evaluated by RNase protection assays using RNA isolated from a variety of human cell lines to characterize and elucidate the nature of this additional AS encoded message.

  14. Expression of MIF and CD74 in leukemic cell lines: correlation to DR expression destiny.

    Science.gov (United States)

    Georgouli, Mirella; Papadimitriou, Lina; Glymenaki, Maria; Patsaki, Valia; Athanassakis, Irene

    2016-06-01

    Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein, which apart from its role as a chaperone dedicated to MHCII molecules, is known to be a high-affinity receptor for macrophage migration inhibitory factor (MIF). The present study aimed to define the roles of CD74 and MIF in the immune surveillance escape process. Towards this direction, the cell lines HL-60, Raji, K562 and primary pre-B leukemic cells were examined for expression and secretion of MIF. Flow cytometry analysis detected high levels of MIF and intracellular/membrane CD74 expression in all leukemic cells tested, while MIF secretion was shown to be inversely proportional to intracellular HLA-DR (DR) expression. In the MHCII-negative cells, IFN-γ increased MIF expression and induced its secretion in HL-60 and K562 cells, respectively. In K562 cells, CD74 (Iip33Iip35) was shown to co-precipitate with HLA-DOβ (DOβ), inhibiting thus MIF or DR binding. Induced expression of DOα in K562 (DOα-DOβ+) cells in different transfection combinations decreased MIF expression and secretion, while increasing surface DR expression. Thus, MIF could indeed be part of the antigen presentation process.

  15. Solve the organ shortage: let the bidding begin!

    Science.gov (United States)

    Kevorkian, J

    2001-01-01

    Commercialization of transplantable human organs is the only sure way to end the crisis of their supply. This is best accomplished by implementing a free, non-profit, nationwide, ultimately global online auction market. It should be independent of the current United Network of Organ Sharing (UNOS) system dealing solely with altruistic donation, and of governmental, sectarian, academic, and other bureaucratic control. The operation of such an auction is described with a hypothetical example. An included provision guarantees equity for poor, uninsured, and indigent recipients. Money accrued can be substantial, and would be disbursed by established formula, with major portions going to donors' families and to special funds to be used to bid for the poor and to defray costs incurred by them. As the organ shortage eases, bid prices should drop, resulting perhaps in eventual altruistic donation. Objections to commericalization based on ethics, bodily sanctity, inequity, pecuniary greed, and the slippery slope tocsin are nullified by cogent arguments and examples. The current situation has worsened despite so-called required request laws, proposed token payments to cover funeral expenses for donor families, and extensive media advertising to spur altruistic donation. Prohibitive national and state laws must be rescinded for the sake of more than 60,000 patients now on lengthening waiting lists. A profession committed to saving lives is duty-bound to endorse, help implement, and participate in an auction system dedicated to that end.

  16. Comprehensive bidding strategies with genetic programming/finite state automata

    International Nuclear Information System (INIS)

    Richter, C.W. Jr.; Sheble, G.B.; Ashlock, D.

    1999-01-01

    This research is an extension of the authors' previous work in double auctions aimed at developing bidding strategies for electric utilities which trade electricity competitively. The improvements detailed in this paper come from using data structures which combine genetic programming and finite state automata termed GP-Automata. The strategies developed by the method described here are adaptive--reacting to inputs--whereas the previously developed strategies were only suitable in the particular scenario for which they had been designed. The strategies encoded in the GP-Automata are tested in an auction simulator. The simulator pits them against other distribution companies (distcos) and generation companies (gencos), buying and selling power via double auctions implemented in regional commodity exchanges. The GP-Automata are evolved with a genetic algorithm so that they possess certain characteristics. In addition to designing successful bidding strategies (whose usage would result in higher profits) the resulting strategies can also be designed to imitate certain types of trading behaviors. The resulting strategies can be implemented directly in on-line trading, or can be used as realistic competitors in an off-line trading simulator

  17. Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1

    International Nuclear Information System (INIS)

    Niu, Xiao-Fang; Liu, Bao-Qin; Du, Zhen-Xian; Gao, Yan-Yan; Li, Chao; Li, Ning; Guan, Yifu; Wang, Hua-Qin

    2011-01-01

    It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors. Leukemic cells were treated with MG132 alone or in combination with resveratrol. Cell viability was investigated using MTT assay, and induction of apoptosis and cell cycle distribution was measured using flow cytometry. Western blot and real-time RT-PCR were used to investigate the expression of FOXO1 and p27 Kip1 . CHIP was performed to investigate the binding of FOXO1 to the p27 Kip1 promoter. Resveratrol strongly reduced cytotoxic activities of proteasome inhibitors against leukemic cells. MG132 in combination with resveratrol caused cell cycle blockade at G1/S transition via p27 Kip1 accumulation. Knockdown of p27 Kip1 using siRNA dramatically attenuated the protective effects of resveratrol on cytotoxic actions of proteasome inhibitors against leukemic cells. Resveratrol induced FOXO1 expression at the transcriptional level, while MG132 increased nuclear distribution of FOXO1. MG132 in combination with resveratrol caused synergistic induction of p27 Kip1 through increased recruitment of FOXO1 on the p27 Kip1 promoter. Resveratrol may have the potential to negate the cytotoxic effects of proteasome inhibitors via regulation of FOXO1 transcriptional activity and accumulation of p27 Kip1

  18. Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia.

    Science.gov (United States)

    Tomonaga, M; Jinnai, I; Tagawa, M; Amenomori, T; Nishino, K; Yao, E; Nonaka, H; Kuriyama, K; Yoshida, Y; Matsuo, T

    1987-02-01

    The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.

  19. Cyclopentenyl cytosine induces apoptosis and increases cytarabine-induced apoptosis in a T-lymphoblastic leukemic cell-line

    NARCIS (Netherlands)

    Verschuur, A. C.; Brinkman, J.; van Gennip, A. H.; Leen, R.; Vet, R. J.; Evers, L. M.; Voûte, P. A.; van Kuilenburg, A. B.

    2001-01-01

    Cyclopentenyl cytosine (CPEC) is a nucleoside-analogue that decreases the concentrations of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells by inhibiting the enzyme CTP synthetase, resulting in a decreased synthesis of RNA and DNA. Low concentrations of dCTP

  20. Co-culture with podoplanin+ cells protects leukemic blast cells with leukemia-associated antigens in the tumor microenvironment.

    Science.gov (United States)

    Lee, Ji Yoon; Han, A-Reum; Lee, Sung-Eun; Min, Woo-Sung; Kim, Hee-Je

    2016-05-01

    Podoplanin+ cells are indispensable in the tumor microenvironment. Increasing evidence suggests that podoplanin may support the growth and metastasis of solid tumors; however, to the best of our knowledge no studies have determined whether or not podoplanin serves a supportive role in acute myeloid leukemia (AML). The effects of co‑culture with podoplanin+ cells on the cellular activities of the leukemic cells, such as apoptosis and cell proliferation, in addition to the expression of podoplanin in leukemic cells, were investigated. Due to the fact that genetic abnormalities are the primary cause of leukemogenesis, the overexpression of the fibromyalgia‑like tyrosine kinase‑3 gene in colony forming units was also examined following cell sorting. Podoplanin+ cells were found to play a protective role against apoptosis in leukemic cells and to promote cell proliferation. Tumor‑associated antigens, including Wilms' tumor gene 1 and survivin, were increased when leukemic cells were co‑cultured with podoplanin+ cells. In combination, the present results also suggest that podoplanin+ cells can function as stromal cells for blast cell retention in the AML tumor microenvironment.

  1. Existence and computation of equilibria of first-price auctions with integral valuations and bids

    DEFF Research Database (Denmark)

    Escamocher, Guillaume; Miltersen, Peter Bro; Santillan, Rocio

    2009-01-01

    We consider existence and computation of symmetric Pure Strategy Nash Equilibrium (PSNE) in single-item, sealed-bid, first-price auctions with integral valuations and bids. For the most general case, we show that existence of PSNE is NP-hard. Then, we present algorithmic results for the case...

  2. 48 CFR 52.214-10 - Contract Award-Sealed Bidding.

    Science.gov (United States)

    2010-10-01

    ... the solicitation, will be most advantageous to the Government considering only price and the price... quantity less than the quantity offered, at the unit prices offered, unless the bidder specifies otherwise in the bid. (d) A written award or acceptance of a bid mailed or otherwise furnished to the...

  3. 47 CFR 27.209 - Designated entities; bidding credits; unjust enrichment.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Designated entities; bidding credits; unjust enrichment. 27.209 Section 27.209 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... 2305-2320 MHz and 2345-2360 MHz Bands § 27.209 Designated entities; bidding credits; unjust enrichment...

  4. 47 CFR 25.401 - Satellite DARS applications subject to competitive bidding.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Satellite DARS applications subject to competitive bidding. 25.401 Section 25.401 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Competitive Bidding Procedures for DARS § 25.401...

  5. 47 CFR 80.1251 - Maritime communications subject to competitive bidding.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime communications subject to competitive... AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Competitive Bidding Procedures § 80.1251 Maritime communications subject to competitive bidding. Mutually exclusive initial applications for VPCSA...

  6. Implementation of the Takeover Bids Directive in the Netherlands : Chapter 12

    NARCIS (Netherlands)

    Cremers, Jan; van Het Kaar, R.H.; Cremers, Jan; Vitols, Sigurt

    2016-01-01

    Chapter dedicated to the Dutch implementation of EU Takeover Bids Directive. The case is particularly interesting because of the strong position of works councils within Dutch companies, including in restructuring situations. Implementation of the Takeover Bids Directive in the Netherlands did not

  7. 48 CFR 14.203-2 - Dissemination of information concerning invitations for bids.

    Science.gov (United States)

    2010-10-01

    ... 14.203-2 Dissemination of information concerning invitations for bids. Procedures concerning display... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Dissemination of information concerning invitations for bids. 14.203-2 Section 14.203-2 Federal Acquisition Regulations System...

  8. Strategic Bidding in Multi-Unit Auctions with Capacity Constrained Bidders

    DEFF Research Database (Denmark)

    Schwenen, Sebastian

    2015-01-01

    This article employs a simple model to describe bidding behavior in multi-unit uniform price procurement auctions when firms are capacity constrained. Using data from the New York City procurement auctions for power generating capacity, I find that firms use simple bidding strategies to coordinate......'s capacities and its profits of undercutting increase....

  9. 30 CFR 260.110 - What bidding systems may MMS use?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What bidding systems may MMS use? 260.110 Section 260.110 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OUTER... MMS use? We will apply a single bidding system selected from those listed in this section to each...

  10. 30 CFR 285.222 - What does MMS do with my bid?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What does MMS do with my bid? 285.222 Section... Energy Leases Competitive Lease Award Process § 285.222 What does MMS do with my bid? (a) If sealed... any proposal submitted will be made by a panel composed of members selected by MMS. The details of the...

  11. The degree of rationality in actual bidding of hydropower at Nord Pool

    DEFF Research Database (Denmark)

    Alnæs, Erik Nicholas; Grøndahl, Roger; Fleten, Stein-Erik

    2013-01-01

    In deregulated electricity markets, power producers bid to sell tomorrow's generation in day-ahead auctions. We analyse bids submitted by three medium to large sized Norwegian reservoir hydropower producers over four two-week periods in 2011. Being price takers, the producers maximize their profits...

  12. Caspase-8 Binding to Cardiolipin in Giant Unilamellar Vesicles Provides a Functional Docking Platform for Bid

    DEFF Research Database (Denmark)

    Jalmar, Olivier; Franc¸ois-Moutal, Liberty; García-Sáez, Ana-Jesus

    2013-01-01

    Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activa...

  13. 47 CFR 22.228 - Cellular rural service area licenses subject to competitive bidding.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular rural service area licenses subject to... Procedures § 22.228 Cellular rural service area licenses subject to competitive bidding. Mutually exclusive initial applications for Cellular Rural Service Area licenses are subject to competitive bidding. The...

  14. 48 CFR 22.1014 - Delay over 60 days in bid opening or commencement of work.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Delay over 60 days in bid... ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Service Contract Act of 1965, as Amended 22.1014 Delay over 60 days in bid opening or commencement of work. If a...

  15. 75 FR 13212 - Proposed Information Collection (Caution to Bidders-Bid Envelopes) Activity: Comment Request

    Science.gov (United States)

    2010-03-18

    ... (Caution to Bidders--Bid Envelopes) Activity: Comment Request AGENCY: Office of Acquisition and Logistics... comment in response to the notice. This notice solicits comments on the information needed to identify bid...: Under the PRA of 1995 (Public Law 104-13; 44 U.S.C. 3501-3521), Federal agencies must obtain approval...

  16. 47 CFR 24.717 - Bidding credits for licenses for frequency Block F.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Bidding credits for licenses for frequency Block F. 24.717 Section 24.717 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON....717 Bidding credits for licenses for frequency Block F. (a) Except with respect to licenses won in...

  17. Coordination of bidding strategies in day-ahead energy and spinning reserve markets

    International Nuclear Information System (INIS)

    Fushuan Wen; David, A.K.

    2002-01-01

    In this paper, the problem of building optimally coordinated bidding strategies for competitive suppliers in day-ahead energy and spinning reserve markets is addressed. It is assumed that each supplier bids 24 linear energy supply functions and 24 linear spinning reserve supply functions, one for each hour, into the energy and spinning reserve markets, respectively, and each market is cleared separately and simultaneously for all the 24 delivery hours. Each supplier makes decisions on unit commitment and chooses the coefficients in the linear energy and spinning reserve supply functions to maximise total benefits, subject to expectations about how rival suppliers will bid in both markets. Two different bidding schemes have been suggested for each hour, and based on them an overall coordinated bidding strategy in the day-ahead energy and spinning reserve market is then developed. Stochastic optimisation models are first developed to describe these two different bidding schemes and a genetic algorithm (GA) is then used to build the optimally coordinated bidding strategies for each scheme and to develop an overall bidding strategy for the day-ahead energy and spinning reserve markets. A numerical example is utilised to illustrate the essential features of the method. (Author)

  18. Fundamental studies of leukemic cell labeling with /sup 111/In-oxine and their applications to cell kinetics in patients with acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Yuhkoh; Matsuda, Shin; Uchida, Tatsumi; Kariyone, Shigeo [Fukushima Medical Coll. (Japan)

    1984-04-01

    Fundamental studies of leukemic cell labeling with /sup 111/In-oxine and their applications to leukemic cell kinetics in five patients with acute myeloblastic leukemia (AML) were examined. Labeling efficiency of leukemic cells was 80.3 +- 3.6% for more than 1 x 10/sup 8/ cells at room temperature for 20 minutes of incubation followed by two times washes. Cell viability determined by means of trypanblue exclusion test was 95.3 +- 2.6%. In vitro elution rate of /sup 111/In from the labeled cells during 12 hours was 10.0 +- 1.2%. The disappearance curves of labeled leukemic cells in AMLs followed a single exponential fashion, and the half time of disappearance (T 1/2) ranged from 9.6 to 31.8 hours. Total blood leukemic cell pool (TBLCP) calculated with the dilution principles of radioisotopes correlated significantly with the leukemic cell counts (LC) in the peripheral blood (Y = 0.32 + 1.94X, r = 0.99). In the studies of organ distribution which were observed and analyzed with gamma camera and computer, labeled leukemic cells passed through lungs within 15 minutes. Radioactivity in the spleen increased rapidly for 30 - 60 minutes, then reached a plateau. Hepatic radioactivity showed a temporary decrease during 10 - 60 minutes following the moderate accumulation in initial 10 minutes. In two cases, bone marrow was visualized 24 hours after the injection. Radioactivity of the leukemic cells isolated from the bone marrow at 22 hours after the injection in one case was one third of the radioactivity in leukemic cells obtained from the peripheral blood at the same time.

  19. Fundamental studies of leukemic cell labeling with 111 In-oxine and their applications to cell kinetics in patients with acute leukemia

    International Nuclear Information System (INIS)

    Takagi, Yuhkoh; Matsuda, Shin; Uchida, Tatsumi; Kariyone, Shigeo

    1984-01-01

    Fundamental studies of leukemic cell labeling with 111 In-oxine and their applications to leukemic cell kinetics in five patients with acute myeloblastic leukemia (AML) were examined. Labeling efficiency of leukemic cells was 80.3 +- 3.6% for more than 1 x 10 8 cells at room temperature for 20 minutes of incubation followed by two times washes. Cell viability determined by means of trypanblue exclusion test was 95.3 +- 2.6%. In vitro elution rate of 111 In from the labeled cells during 12 hours was 10.0 +- 1.2%. The disappearance curves of labeled leukemic cells in AMLs followed a single exponential fashion, and the half time of disappearance (T 1/2) ranged from 9.6 to 31.8 hours. Total blood leukemic cell pool (TBLCP) calculated with the dilution principles of radioisotopes correlated significantly with the leukemic cell counts (LC) in the peripheral blood (Y = 0.32 + 1.94X, r = 0.99). In the studies of organ distribution which were observed and analized with gamma camera and computer, labeled leukemic cells passed through lungs within 15 minutes. Radioactivity in the spleen increased rapidly for 30 - 60 minutes, then reached a plateau. Hepatic radioactivity showed a temporary decrease during 10 - 60 minutes following the moderate accumulation in initial 10 minutes. In two cases, bone marrow was visualized 24 hours after the injection. Radioactivity of the leukemic cells isolated from the bone marrow at 22 hours after the injection in one case was one third of the radioactivity in leukemic cells obtained from the peripheral blood at the same time. (author)

  20. Long Term Expected Revenue of Wind Farms Considering the Bidding Admission Uncertainty

    DEFF Research Database (Denmark)

    Bashi, Mazaher Haji; Yousefi, G.R.; Bak, Claus Leth

    2016-01-01

    in the long term expected revenue of wind farms. We show that this consideration could perfectly explain the observed bid shading behavior of wind farm owners. We use a novel market price model with a stochastic model of a wind farm to derive indices describing the uncertainty of bidding admission....... The optimal behavior of the wind farm is then obtained by establishing a multi objective optimization problem and subsequently solved using genetic algorithm. The method is applied to the analysis of long term bidding behavior of a wind farm participating in a Pay-as-Bid (PAB) auction such as Iran Electricity...... Market (IEM). The results demonstrate that wind farm owners change their bid shading behavior in a PAB Auction. However, the expected revenue of the wind farm will also decrease in a PAB auction. As a result, it is not recommended to make an obligation for the wind farms to participate in a PAB auction...

  1. Sequential bidding in day-ahead auctions for spot energy and power systems reserve

    International Nuclear Information System (INIS)

    Swider, Derk J.

    2005-01-01

    In this paper a novel approach for sequential bidding on day-ahead auction markets for spot energy and power systems reserve is presented. For the spot market a relatively simple method is considered as a competitive market is assumed. For the reserve market one bidder is assumed to behave strategically and the behavior of the competitors is summarized in a probability distribution of the market price. This results in a method for sequential bidding, where the bidding prices and capacities on the spot and reserve markets are calculated by maximizing a stochastic non-linear objective function of expected profit. With an exemplary application is shown that the trading sequence leads to increasing bidding capacities and prices in the reverse rank number of the markets. Hence, the consideration of a defined trading sequence greatly influences the mathematical representation of the optimal bidding behavior under price uncertainty in day-ahead auctions for spot energy and power systems reserve. (Author)

  2. DNA repair and DNA synthesis in leukemic and virus infected cells

    International Nuclear Information System (INIS)

    Tuschl, H.; Altmann, H.; Kovac, R.; Topaloglou, A.; Stacher, A.; Fanta, D.

    1978-09-01

    Autoradiographic determinations of unscheduled DNA synthesis in peripheral lymphocytes of leukemic patients showed strongly different results according to various types of disease of different forms of therapy, respectively. Similar investigations performed with lymphocytes of Herpes simplex infected persons during symptom-free intervals revealed imbalances of the repair system caused by virus infection. BND cellulose chromatography and measurement of 3 H-thymidine incorporation into single- and double stranded DNA fractions showed an increase in velocity of the rejoining process, but a decrease in total incorporation. Because of these results and the demonstration of the supercoiled structure of DNA it is suggested that virusinfections cause a faster rejoining of gaps, but at the same time leave a number of failures within DNA unrecognized. (author)

  3. Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.

    Science.gov (United States)

    Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Murofushi, N; Nishimura, H

    2000-08-01

    Epidemiological studies indicate that high intakes of fruits and vegetables are associated with a reduced risk of cancer, and several plant-derived drugs have been developed in medical oncology. Since only a small part of the flora has been tested for any kind of bioactivity, we chose small fruits as sources of differentiation-inducing activity against HL-60 leukemic cells. We have prepared juices from various small fruits that grow mainly in the northern part of Japan. Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly induced differentiation of HL-60 cells to monocyte/macrophage characteristics in a concentration-dependent manner as indicated by histochemical and biochemical examinations.

  4. Hepatosplenic and renal candidiasis in leukemic patients: CT spectrum before and after therapy

    International Nuclear Information System (INIS)

    Shirkhoda, A.

    1986-01-01

    Abdominal CT performed in 14 leukemic patients with systemic candidiasis and involvement of the liver, spleen, or kidneys revealed numerous low-density lesions in ten livers (71%), eight spleens (57%), and in the kidneys of three patients (21%). Biopsy of all livers and of three kidneys proved hepatic candidiasis in all (100%) and renal candidiasis in three patients (21%). After treatment with amphotericin B and splenectomy (one patient), CT disclosed abnormal livers in eleven (80%) patients, abnormal spleens in seven (53%), and abnormal kidneys in three patients (21%). Rebiopsy disclosed Candida infection in all livers and all abnormal kidneys, so the patients were treated with liposomal amphotericin B. Although the patients became asymptomatic, CT continued to show abnormal livers in five (35%) and abnormal spleens in two (16%) (the previously abnormal kidneys became normal). Rebiopsy of the abnormal livers showed focal fibrosis and necrosis. These findings emphasize the importance of clinical and pathologic correlation of CT appearance

  5. DENTAL CONSIDERATIONS FOR LEUKEMIC PEDIATRIC PATIENTS: AN UPDATED REVIEW FOR GENERAL DENTAL PRACTITIONER.

    Science.gov (United States)

    Lowal, Kholoud A; Alaizari, Nader Ahmed; Tarakji, Bassel; Petro, Waleed; Hussain, Khaja Amjad; Altamimi, Mohamed Abdullah Alsakran

    2015-10-01

    The early signs of leukemia can usually manifest in the oral cavity due to infiltration of leukemic cells or due to associated decline in normal marrow elements, especially in the acute phase of leukemia, as common lesions at this stage of the disease can be screened and diagnosed by the dentist. Therefore, the dental community should be aware of the oral manifestations of leukemia and oral complications of anticancer treatment. This can eliminate the oral symptoms of the disease and to improve quality of life for these patients. An extensive search in PubMed line using a combination of terms like "leukemia, children, dental, Acute lymphoblastic leukemia, pediatric" for last ten years was made. Reviews and case reports concerned about acute lymphoblastic leukemia in children were all collected and analyzed and data were extracted. Accordingly, the aim of this review is to highlight on the oral presentations of leukemia in children attending dental clinics and the management of its undesirable side effects.

  6. Aberrant methylation of the M-type phospholipase A2 receptor gene in leukemic cells

    International Nuclear Information System (INIS)

    Menschikowski, Mario; Platzbecker, Uwe; Hagelgans, Albert; Vogel, Margot; Thiede, Christian; Schönefeldt, Claudia; Lehnert, Renate; Eisenhofer, Graeme; Siegert, Gabriele

    2012-01-01

    The M-type phospholipase A2 receptor (PLA2R1) plays a crucial role in several signaling pathways and may act as tumor-suppressor. This study examined the expression and methylation of the PLA2R1 gene in Jurkat and U937 leukemic cell lines and its methylation in patients with myelodysplastic syndrome (MDS) or acute leukemia. Sites of methylation of the PLA2R1 locus were identified by sequencing bisulfite-modified DNA fragments. Methylation specific-high resolution melting (MS-HRM) analysis was then carried out to quantify PLA2R1 methylation at 5-CpG sites identified with differences in methylation between healthy control subjects and leukemic patients using sequencing of bisulfite-modified genomic DNA. Expression of PLA2R1 was found to be completely down-regulated in Jurkat and U937 cells, accompanied by complete methylation of PLA2R1 promoter and down-stream regions; PLA2R1 was re-expressed after exposure of cells to 5-aza-2´-deoxycytidine. MS-HRM analysis of the PLA2R1 locus in patients with different types of leukemia indicated an average methylation of 28.9% ± 17.8%, compared to less than 9% in control subjects. In MDS patients the extent of PLA2R1 methylation significantly increased with disease risk. Furthermore, measurements of PLA2R1 methylation appeared useful for predicting responsiveness to the methyltransferase inhibitor, azacitidine, as a pre-emptive treatment to avoid hematological relapse in patients with high-risk MDS or acute myeloid leukemia. The study shows for the first time that PLA2R1 gene sequences are a target of hypermethylation in leukemia, which may have pathophysiological relevance for disease evolution in MDS and leukemogenesis

  7. Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1.

    Science.gov (United States)

    Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

    2017-02-01

    As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK-HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated.

  8. Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1

    Science.gov (United States)

    Abdelbaset-Ismail, A; Borkowska-Rzeszotek, S; Kubis, E; Bujko, K; Brzeźniakiewicz-Janus, K; Bolkun, L; Kloczko, J; Moniuszko, M; Basak, G W; Wiktor-Jedrzejczak, W; Ratajczak, M Z

    2017-01-01

    As a crucial arm of innate immunity, the complement cascade (ComC) is involved both in mobilization of normal hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood and in their homing to BM. Despite the fact that ComC cleavage fragments alone do not chemoattract normal HSPCs, we found that leukemia cell lines as well as clonogenic blasts from chronic myeloid leukemia and acute myeloid leukemia patients respond robustly to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. This finding was supported by the detection of C3a and C5a receptors in cells from human malignant hematopoietic cell lines and patient blasts at the mRNA (reverse transcriptase-polymerase chain reaction) and protein level (fluorescence-activated cell sorting), and by the demonstration that these receptors respond to stimulation by C3a and C5a by phosphorylation of p42/44 and p38 mitogen-activated protein kinases (MAPK), and protein kinase B (PKB/AKT). We also found that inducible heme oxygenase 1 (HO-1) is a negative regulator of ComC-mediated trafficking of leukemic cells, and that stimulation of leukemic cells by C3 or C5 cleavage fragments activates p38 MAPK, which downregulates HO-1 expression, rendering cells more mobile. We conclude that activation of the ComC in leukemia/lymphoma patients (for example, as a result of accompanying infections) enhances the motility of malignant cells and contributes to their spread in a p38 MAPK–HO-1-dependent manner. Therefore, inhibition of p38 MAPK or upregulation of HO-1 by small-molecule modulators would have a beneficial effect on ameliorating cell migration-mediated expansion of leukemia/lymphoma cells when the ComC becomes activated. PMID:27451975

  9. [Expression of c-MPL in leukemic stem cells from acute myeloid leukemia patients].

    Science.gov (United States)

    Yu, Pei; Qiu, Shao-Wei; Rao, Qing; Lin, Dong; Xing, Hai-Yan; Tang, Ke-Jing; Tian, Zheng; Wang, Min; Wang, Jian-Xiang

    2012-10-01

    This study was aimed to investigate the expression of c-MPL in acute myeloid leukemia (AML) and the correlation of the c-MPL expression with CD34 and CD38, so as to define the expression of c-MPL in leukemic stem cells. The expression levels of CD34, CD38 and c-MPL were detected by flow cytometry in bone marrow cells from 29 newly diagnosed AML patients. The relationship of c-MPL positive cell ratio with clinical parameters and correlation of c-MPL with CD34 and CD38 expression in AML patients were analyzed. The results showed that expression level of c-MPL in AML patients was significantly higher than that of normal controls (P MPL did not correlate with age, sex, white blood cell count, AML1-ETO fusion gene and remission after chemotherapy, but the expression of c-MPL in M2 and M5 patients was higher than that of normal control (P MPL in CD34 positive AML patients was obviously higher than that in CD34 negative AML patients (P MPL was significantly higher expressed in CD34(+) cells than that in CD34(-) cells (P MPL expression was not significantly different between CD34(+)CD38(-) and CD34(+)CD38(-) cell groups. Positive correlation between c-MPL and CD34 expression was observed (r = 0.380, P = 0.042). It is concluded that expression of c-MPL is higher in AML patients, and positively correlates with the expression level of CD34. The c-MPL expresses in leukemic stem cells.

  10. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

    Science.gov (United States)

    Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T

    2015-04-01

    Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

  11. Intramuscular leukemic relapse: clinical signs and imaging findings. A multicentric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Surov, Alexey [Martin Luther University Halle-Wittenberg, Department of Radiology, Halle (Germany); University of Leipzig, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Kiratli, Hayyam [Hacettepe University School of Medicine, Department of Ophthalmology, Ankara (Turkey); Im, Soo Ah [Seoul St. Mary' s Hospital, Department of Radiology, Seoul (Korea, Republic of); Manabe, Yasuhiro [National Hospital Organization Okayama Medical Center, Department of Neurology, Okayama (Japan); O' Neill, Alibhe; Shinagare, Atul B. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Spielmann, Rolf Peter [Martin Luther University Halle-Wittenberg, Department of Radiology, Halle (Germany)

    2014-09-26

    Leukemia is a group of malignant diseases involving peripheral blood and bone marrow. Extramedullary tumor manifestation in leukemia can also occur. They more often involve lymph nodes, skin, and bones. Intramuscular leukemic relapse (ILR) is very unusual. The aim of this analysis was to summarize the reported data regarding clinical signs and radiological features of ILR. The PubMed database was searched for publications related to ILR. After an analysis of all identified articles, 20 publications matched the inclusion criteria. The authors of the 20 publications were contacted and provided imaging of their cases for review. The following were recorded: age, gender, primary diagnosis, clinical signs, pattern, localization and size of the intramuscular leukemic relapse. Images of 16 patients were provided [8 computer tomographic (CT) images and 15 magnetic resonance images, MRI]. Furthermore, one patient with ILR was identified in our institutional database. Therefore, images of 17 patients were available for further analysis. Overall, 32 cases with ILR were included in the analysis. In most cases acute myeloid leukemia was diagnosed. Most ILRs were localized in the extremities (44 %) and in the extraocular muscles (44 %). Clinically, ILR manifested as local pain, swelling and muscle weakness. Radiologically, ILR presented most frequently with diffuse muscle infiltration. On postcontrast CT/MRI, most lesions demonstrated homogeneous enhancement. ILRs were hypo-/isointense on T1w and hyperintense on T2w images. ILR manifests commonly as focal pain, swelling and muscle weakness. ILR predominantly involved the extraocular musculature and the extremities. Radiologically, diffuse muscle infiltration was the most common imaging finding. (orig.)

  12. Land bidding game with conflicting interest and its quantum solution

    Science.gov (United States)

    Situ, Haozhen; Alonso-Sanz, Ramón; Li, Lvzhou; Zhang, Cai

    Recently, the first conflicting interest quantum game based on the nonlocality property of quantum mechanics has been introduced in A. Pappa, N. Kumar, T. Lawson, M. Santha, S. Y. Zhang, E. Diamanti and I. Kerenidis, Phys. Rev. Lett. 114 (2015) 020401. Several quantum games of the same genre have also been proposed subsequently. However, these games are constructed from some well-known Bell inequalities, thus are quite abstract and lack of realistic interpretations. In the present paper, we modify the common interest land bidding game introduced in N. Brunner and N. Linden, Nat. Commun. 4 (2013) 2057, which is also based on nonlocality and can be understood as two companies collaborating in developing a project. The modified game has conflicting interest and reflects the free rider problem in economics. Then we show that it has a fair quantum solution that leads to better outcome. Finally, we study how several types of paradigmatic noise affect the outcome of this game.

  13. 31 CFR 356.12 - What are the different types of bids and do they have specific requirements or restrictions?

    Science.gov (United States)

    2010-07-01

    ...) Treasury bills. A competitive bid must show the discount rate bid, expressed with three decimals in .005... competitively, either at a single yield or discount rate, or at different yields or discount rates. However, a competitive bid at a single yield or discount rate that exceeds 35 percent of the offering amount will be...

  14. 48 CFR 3.104-4 - Disclosure, protection, and marking of contractor bid or proposal information and source...

    Science.gov (United States)

    2010-10-01

    ... otherwise authorized by law or regulation. Any release containing contractor bid or proposal information or..., and marking of contractor bid or proposal information and source selection information. 3.104-4... marking of contractor bid or proposal information and source selection information. (a) Except as...

  15. Defective quorum sensing of acute lymphoblastic leukemic cells: evidence of collective behavior of leukemic populations as semi-autonomous aberrant ecosystems

    Science.gov (United States)

    Patel, Sapan J; Dao, Su; Darie, Costel C; Clarkson, Bayard D

    2016-01-01

    Quorum sensing (QS) is a generic term used to describe cell-cell communication and collective decision making by bacterial and social insects to regulate the expression of specific genes in controlling cell density and other properties of the populations in response to nutrient supply or changes in the environment. QS mechanisms also have a role in higher organisms in maintaining homeostasis, regulation of the immune system and collective behavior of cancer cell populations. In the present study, we used a p190BCR-ABL driven pre-B acute lymphoblastic leukemia (ALL3) cell line derived from the pleural fluid of a terminally ill patient with ALL to test the QS hypothesis in leukemia. ALL3 cells don’t grow at low density (LD) in liquid media but grow progressively faster at increasingly high cell densities (HD) in contrast to other established leukemic cell lines that grow well at very low starting cell densities. The ALL3 cells at LD are poised to grow but shortly die without additional stimulation. Supernates of ALL3 cells (HDSN) and some other primary cells grown at HD stimulate the growth of the LD ALL3 cells without which they won’t survive. To get further insight into the activation processes we performed microarray analysis of the LD ALL3 cells after stimulation with ALL3 HDSN at days 1, 3, and 6. This screen identified several candidate genes, and we linked them to signaling networks and their functions. We observed that genes involved in lipid, cholesterol, fatty acid metabolism, and B cell activation are most up- or down-regulated upon stimulation of the LD ALL3 cells using HDSN. We also discuss other pathways that are differentially expressed upon stimulation of the LD ALL3 cells. Our findings suggest that the Ph+ ALL population achieves dominance by functioning as a collective aberrant ecosystem subject to defective quorum-sensing regulatory mechanisms. PMID:27429840

  16. A Comparative Study on the Bidding Behavior of Pay as Bid and Uniform Price Electricity Market Players

    DEFF Research Database (Denmark)

    Haji Bashi, Mazaher; Khazraj, Hesam; Bak, Claus Leth

    2018-01-01

    High prices are expected for high demand times in the electricity markets and vice versa. The System Capacity Margin (SCM) demonstrates the abundance of electricity in the market. Naturally, higher SCM causes to lower price but, the players' behavior distortions have been frequently addressed...... in the literature. The overall producers’ bidding behaviors participating in Iran Electricity Market (IEM) as the low wind penetrated case and the Danish Electricity Market (DEM) as a high wind penetrated case are studied in this paper. An index is introduced to describe the overall market players’ behaviors....... Considering the players' behavior and using adaptive Neuro-fuzzy inference system, a model is derived. Although the total trend of prices is descending while the SCM increases, the results show some unexpected behaviors in IEM. Finally, players' biding behavior are compared in DEM and IEM. Markov transition...

  17. Optimal Bidding Strategies for Wind Power Producers in the Day-ahead Electricity Market

    Directory of Open Access Journals (Sweden)

    Xiaolin Liu

    2012-11-01

    Full Text Available Wind Power Producers (WPPs seek to maximize profit and minimize the imbalance costs when bidding into the day-ahead market, but uncertainties in the hourly available wind and forecasting errors make the bidding risky. This paper assumes that hourly wind power output given by the forecast follows a normal distribution, and proposes three different bidding strategies, i.e., the expected profit-maximization strategy (EPS, the chance-constrained programming-based strategy (CPS and the multi-objective bidding strategy (ECPS. Analytical solutions under the three strategies are obtained. Comparisons among the three strategies are conducted on a hypothetical wind farm which follows the Spanish market rules. Results show that bid under the EPS is highly dependent on market clearing price, imbalance prices, and also the mean value and standard deviation of wind forecast, and that bid under the CPS is largely driven by risk parameters and the mean value and standard deviation of the wind forecast. The ECPS combining both EPS and CPS tends to choose a compromise bid. Furthermore, the ECPS can effectively control the tradeoff between expected profit and target profit for WPPs operating in volatile electricity markets.

  18. Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

    Science.gov (United States)

    Driak, D; Dvorska, M; Bolehovska, P; Svandova, I; Novotny, J; Halaska, M

    2014-01-01

    The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

  19. Demand bidding construction for a large consumer through a hybrid IGDT-probability methodology

    International Nuclear Information System (INIS)

    Zare, Kazem; Moghaddam, Mohsen Parsa; Sheikh El Eslami, Mohammad Kazem

    2010-01-01

    This paper provides a technique to derive the bidding strategy in the day-ahead market for a large consumer that procures its electricity demand in both day-ahead market and a subsequent adjustment market. It is considered that hourly market prices are normally distributed and this correlation is modeled by variance-covariance matrix. The uncertainty of procurement cost is modeled using concepts derived from information gap decision theory which allows deriving robust bidding strategies with respect to price volatility. First Order Reliability Method is applied to construct the robust bidding curve. The proposed technique is illustrated through a realistic case study. (author)

  20. Use of Bidding Supply to Attend State Emergency Caused by Poor Planning and its Consequences

    Directory of Open Access Journals (Sweden)

    Clayton Gomes de Medeiros

    2016-10-01

    Full Text Available The interpretation of the law inherent in bidding in the country has been the subject of legal discussion, especially as the bidding exemption from the institute, particularly when justified in finding emergency situation, which requires the public administrator prompt and effective steps to eradicate or, least minimize the consequences harmful to the community. However, the biggest dilemma is to characterize the application possibilities of the legal provision, since with the passage of time has glimpsed the jurisprudential understanding change towards the dispensability of the bidding event when the emergency is the result of negligence of Public Administration.

  1. Study of impacts of physical contracts and financial contracts on bidding strategies of GENCOs

    International Nuclear Information System (INIS)

    Xiaoling Chen; He, Y.; Song, Y.H.

    2004-01-01

    This paper studies the impacts of physical contracts and financial contracts on the bidding strategies of GENCOs, including Physical Bilateral Contracts, Contracts for Difference (CfDs), Call Options and Put Options under discriminatory pricing mechanism. The integrated bidding decision model is applied, which has three main modules - probabilistic local marginal price simulator, market-oriented unit commitment model and multi-criteria decision system. The numerical results show that the GENCO will choose different bidding strategies if it holds different types of contract. The results also suggest that CfDs have the best performance for risk alleviation. (author)

  2. A comparison of pay-as-bid and marginal pricing in electricity markets

    Science.gov (United States)

    Ren, Yongjun

    This thesis investigates the behaviour of electricity markets under marginal and pay-as-bid pricing. Marginal pricing is believed to yield the maximum social welfare and is currently implemented by most electricity markets. However, in view of recent electricity market failures, pay-as-bid has been extensively discussed as a possible alternative to marginal pricing. In this research, marginal and pay-as-bid pricing have been analyzed in electricity markets with both perfect and imperfect competition. The perfect competition case is studied under both exact and uncertain system marginal cost prediction. The comparison of the two pricing methods is conducted through two steps: (i) identify the best offer strategy of the generating companies (gencos); (ii) analyze the market performance under these optimum genco strategies. The analysis results together with numerical simulations show that pay-as-bid and marginal pricing are equivalent in a perfect market with exact system marginal cost prediction. In perfect markets with uncertain demand prediction, the two pricing methods are also equivalent but in an expected value sense. If we compare from the perspective of second order statistics, all market performance measures exhibit much lower values under pay-as-bid than under marginal pricing. The risk of deviating from the mean is therefore much higher under marginal pricing than under pay-as-bid. In an imperfect competition market with exact demand prediction, the research shows that pay-as-bid pricing yields lower consumer payments and lower genco profits. This research provides quantitative evidence that challenges some common claims about pay-as-bid pricing. One is that under pay-as-bid, participants would soon learn how to offer so as to obtain the same or higher profits than what they would have obtained under marginal pricing. This research however shows that, under pay-as-bid, participants can at best earn the same profit or expected profit as under marginal

  3. Multi-Objective Bidding Strategy for Genco Using Non-Dominated Sorting Particle Swarm Optimization

    Science.gov (United States)

    Saksinchai, Apinat; Boonchuay, Chanwit; Ongsakul, Weerakorn

    2010-06-01

    This paper proposes a multi-objective bidding strategy for a generation company (GenCo) in uniform price spot market using non-dominated sorting particle swarm optimization (NSPSO). Instead of using a tradeoff technique, NSPSO is introduced to solve the multi-objective strategic bidding problem considering expected profit maximization and risk (profit variation) minimization. Monte Carlo simulation is employed to simulate rivals' bidding behavior. Test results indicate that the proposed approach can provide the efficient non-dominated solution front effectively. In addition, it can be used as a decision making tool for a GenCo compromising between expected profit and price risk in spot market.

  4. Liquidity Shocks, Market Maker Turnover, and Bidding Behavior in Treasury Auctions

    DEFF Research Database (Denmark)

    Gonzalez-Eiras, Martin; Rudiger, Jesper

    2017-01-01

    aggressively. They also bid more aggressively for existing securities that are reissued when the regulation tightens the requirements for secondary market participation. Consistent with regulations which imply that auctioned securities are not a prime source of liquidity, we find that banks which face...... liquidity needs bid less aggressively for them. A novel implication of our results is that in institutional settings that feature turnover of market makers, bidding behavior should be modeled in a dynamic setting. We introduce a dynamic model and show that static estimates over-predict true valuations when...

  5. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods.

    Science.gov (United States)

    Øbro, Nina F; Ryder, Lars P; Madsen, Hans O; Andersen, Mette K; Lausen, Birgitte; Hasle, Henrik; Schmiegelow, Kjeld; Marquart, Hanne V

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and/or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative immunophenotype and antigen modulation) that highlight important methodological pitfalls. These findings demonstrate that with sufficient experience, flow cytometry is reliable for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia, although rare cases require supplementary PCR-based monitoring.

  6. ROLE OF LEUKEMIC STEM CELLS IN THE CHRONIC MYELOID LEUKEMIA PATHOGENESIS

    Directory of Open Access Journals (Sweden)

    Sviezhentseva IO

    2016-09-01

    Full Text Available The presence of leukemic stem cells (LSC in the bone marrow of patients with chronic myeloid leukemia (CML is the cause of relapses as a result of the treatment with chemotherapeutic agents and target therapy drugs. This is due to the ability of LSC to attach itself to the microenvironment cells and to remain at rest for a long time. Vascular and osteoblasts niche play a very important role in this process. However, for being in G0 phase LSC have direct contact with the cellular elements of bone marrow microenvironment. So LSK contact with mesenchymal cells of bone marrow using the appendixes, connecting components invaginations and lint. The cadherins and integrins are important in the interaction of osteoblasts niche. They are able to activate intracellular signaling cascades that provide resting state of LSK. In addition, a bone marrow niche provides changes of LSC oxidative metabolism, which also plays an important role for cell entry into the G0 phase. Further, LSC also have certain physiological properties, which play an important role in the drug resistance formation, particularly drugs with targeted actions - tyrosine kinase inhibitors. LSK characterized by a high level of BCR-ABL expression and their population can have a lot of point mutations in the bcr-abl gene in the same patient. This leads to the fact that the taken medicines dose does not act against LSK, reducing the number of a whole leukemic cells clone. However, complete LSC elimination from the the patient’s bone marrow need search the main differences between the LSC and normal HSC. After the literature analysis it was found that LSC have several significant differences such as the ability to cause leukemia during the transplantation to immunodeficient animals, this leukemia is morphologically and phenotypically similar to the original tumor, in addition the LSC can be transmitted from animal to animal. In addition, the LSC is also characterized by the mutations presence

  7. Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic cells with impact on metastasis

    International Nuclear Information System (INIS)

    Prathivadhi-Bhayankaram, Sruti V.; Ning, Jianhao; Mimlitz, Michael; Taylor, Carolyn; Gross, Erin; Nichols, Michael; Guck, Jochen; Ekpenyong, Andrew E.

    2016-01-01

    Although most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis therapy. Surprisingly, emerging evidence suggests that certain anti-cancer drugs such as paclitaxel and doxorubicin can actually promote metastasis, but the mechanism(s) behind their pro-metastatic effects are still unclear. Here, we use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation, to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that leukemic cancer cells treated with doxorubicin and daunorubicin, commonly used anti-cancer drugs, have over 100% longer transit times through the device, compared to untreated leukemic cells. Such delays in the microcirculation are known to promote extravasation of cells, a key step in the metastatic cascade. Furthermore, we report a significant (p < 0.01) increase in the chemotactic migration of the doxorubicin treated leukemic cells. Both enhanced retention in the microcirculation and enhanced migration following chemotherapy, are pro-metastatic effects which can serve as new targets for anti-metastatic drugs. - Highlights: • Doxorubicin enhances migration of leukemic cancer cells before cell death. • Doxorubicin and Daunorubicin stiffen and delay cells in mimicked microcirculation. • Some cancer drugs cause changes in cell mechanics that lead to pro-metastatic effects. • Cell mechanics becomes a new target for anti-metastatic drugs.

  8. Noninvasive identification of subcellular organization and nuclear morphology features associated with leukemic cells using light-scattering spectroscopy

    Science.gov (United States)

    Hsiao, Austin; Hunter, Martin; Greiner, Cherry; Gupta, Sharad; Georgakoudi, Irene

    2011-03-01

    Leukemia is the most common and deadly cancer among children and one of the most prevalent cancers among adults. Improvements in its diagnosis and monitoring of leukemic patients could have a significant impact in their long-term treatment. We demonstrate that light-scattering spectroscopy (LSS)-based approaches could serve as a tool to achieve this goal. Specifically, we characterize the light scattering properties of leukemic (NALM-6) cells and compare them to those of normal lymphocytes and granulocytes in the 440-710 nm range, over +/-4 deg about the exact backscattering direction. We find that the LSS spectra are well described by an inverse power-law wavelength dependence, with a power exponent insensitive to the scattering angle but significantly higher for leukemic cells than for normal leukocytes. This is consistent with differences in the subcellular morphology of these cells, detected in differential interference contrast images. Furthermore, the residual light-scattering signal, extracted after subtracting the inverse power-law fit from the data, can be analyzed assuming a Gaussian distribution of spherical scatterers using Mie theory. This analysis yields scatterer sizes that are consistent with the diameters of cell nuclei and allows the detection of the larger nuclei of NALM-6 cells compared to those of lymphocytes and granulocytes.

  9. Apoptosis induction in MV4-11 and K562 human leukemic cells by Pereskia sacharosa (Cactaceae) leaf crude extract.

    Science.gov (United States)

    Asmaa, Mat Jusoh Siti; Al-Jamal, Hamid Ali Nagi; Ang, Cheng Yong; Asan, Jamaruddin Mat; Seeni, Azman; Johan, Muhammad Farid

    2014-01-01

    Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.

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

    Directory of Open Access Journals (Sweden)

    Kazuya Takahashi

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

  11. Towards The Generation of Functionalized Magnetic Nanowires to Target Leukemic Cells

    KAUST Repository

    Alsharif, Nouf

    2016-04-01

    In recent years, magnetic nanowires (NWs) have been widely used for their therapeutic potential in biomedical applications. The use of iron (Fe) NWs combines two important properties, biocompatibility and remote manipulation by magnetic fields. In addition the NWs can be coated and functionalized to target cells of interest and, upon exposure to an alternating magnetic field, have been shown to induce cell death on several types of adherent cells, including several cancer cell types. For suspension cells, however, using these NWs has been much less effective primarily due to the free-floating nature of the cells minimizing the interaction between them and the NWs. Leukemic cells express higher levels of the cell surface marker CD44 (Braumüller, Gansauge, Ramadani, & Gansauge, 2000), compared to normal blood cells. The goal of this study was to functionalize Fe NWs with a specific monoclonal antibody towards CD44 in order to target leukemic cells (HL-60 cells). This approach is expected to increase the probability of a specific binding to occur between HL-60 cells and Fe NWs. Fe NWs were fabricated with an average diameter of 30-40 nm and a length around 3-4 μm. Then, they were coated with both 3-Aminopropyl-triethoxysilane and bovine serum albumin (BSA) in order to conjugate them with an anti-CD44 antibody (i.e. anti-CD44-iron NWs). The antibody interacts with the amine group in the BSA via the 1-Ethyl-3-3-dimethylaminopropyl-carbodiimide and N-Hydroxysuccinimide coupling. The NWs functionalization was confirmed using a number of approaches including: infrared spectroscopy, Nanodrop to measure the concentration of CD44 antibody, as well as fluorescent-labeled secondary antibody staining to detect the primary CD44 antibody. To confirm that the anti-CD44-iron NWs and bare Fe NWs, in the absence of a magnetic field, were not toxic to HL-60 cells, cytotoxicity assays using XTT (2,3-Bis-2-Methoxy-4-Nitro-5-Sulfophenyl-2H-Tetrazolium-5-Carboxanilide) were performed and

  12. Supplier's optimal bidding strategy in electricity pay-as-bid auction: Comparison of the Q-learning and a model-based approach

    International Nuclear Information System (INIS)

    Rahimiyan, Morteza; Rajabi Mashhadi, Habib

    2008-01-01

    In this paper, the bidding decision making problem in electricity pay-as-bid auction is studied from a supplier's point of view. The bidding problem is a complicated task, because of suppliers' uncertain behaviors and demand fluctuation. In a specific case, in which, the market clearing price (MCP) is considered as a continuous random variable with a known probability distribution function (PDF), an analytic solution is proposed. The suggested solution is generalized to consider the effect of supplier market power due to transmission congestion. As a result, an algebraic equation is developed to compute optimal offering price. The basic assumption in this approach is to take the known probabilistic model for the MCP. The above-mentioned method, called model-based approach, is not more applicable in a realistic situation. In order to overcome the drawback of this method, which needs information about the MCP and its PDF, the supplier learns from past experiences using the Q-learning algorithm to find out the optimal bid price. The simulation results of the model-based and Q-learning methods are compared on a studied system. It is shown that a supplier using the Q-learning algorithm is able to find the optimal bidding strategy similar to one obtained by the model-based approach. Furthermore, to analyze a more realistic situation, the suppliers' behaviors are modeled using a multi-agent system. Simulation results illustrate that the studied supplier finds the optimal bidding strategy in power market using the Q-learning algorithm. (author)

  13. Analysis of General Accounting Office Bid Protest Decisions on A-76 Studies

    National Research Council Canada - National Science Library

    Russial, Paul

    2003-01-01

    .... Historically, industry has successfully protested a high percentage of A-76 procurements. This thesis examines General Accounting Office A-76 bid protest decisions issued between 5 February 1996 and 23 December 2002...

  14. A Data-Driven Bidding Model for a Cluster of Price-Responsive Consumers of Electricity

    DEFF Research Database (Denmark)

    Saez Gallego, Javier; Morales González, Juan Miguel; Zugno, Marco

    2016-01-01

    This paper deals with the market-bidding problem of a cluster of price-responsive consumers of electricity. We develop an inverse optimization scheme that, recast as a bilevel programming problem, uses price-consumption data to estimate the complex market bid that best captures the price......-response of the cluster. The complex market bid is defined as a series of marginal utility functions plus some constraints on demand, such as maximum pick-up and drop-off rates. The proposed modeling approach also leverages information on exogenous factors that may influence the consumption behavior of the cluster, e...... can be largely captured in the form of a complex market bid, so that this could be ultimately used for the cluster to participate in the wholesale electricity market....

  15. 48 CFR 52.214-7 - Late submissions, modifications, and withdrawals of bids.

    Science.gov (United States)

    2010-10-01

    ... transmitted through an electronic commerce method authorized by the IFB, it was received at the initial point... Government processes resume. (e) Bids may be withdrawn by written notice received at any time before the...

  16. Strategic bidding of generating units in competitive electricity market with considering their reliability

    International Nuclear Information System (INIS)

    Soleymani, S.; Ranjbar, A.M.; Shirani, A.R.

    2008-01-01

    In the restructured power systems, they are typically scheduled based on the offers and bids to buy and sell energy and ancillary services (AS) subject to operational and security constraints. Generally, no account is taken of unit reliability when scheduling it. Therefore generating units have no incentive to improve their reliability. This paper proposes a new method to obtain the equilibrium points for reliability and price bidding strategy of units when the unit reliability is considered in the scheduling problem. The proposed methodology employs the supply function equilibrium (SFE) for modeling a unit's bidding strategy. Units change their bidding strategies and improve their reliability until Nash equilibrium points are obtained. GAMS (general algebraic modeling system) language has been used to solve the market scheduling problem using DICOPT optimization software with mixed integer non-linear programming. (author)

  17. A dynamic replicator model of the players' bids in an oligopolistic electricity market

    International Nuclear Information System (INIS)

    Sahraei-Ardakani, Mostafa; Rahimi-Kian, Ashkan

    2009-01-01

    In this paper, the replicator dynamics of the power suppliers' bids in an oligopolistic electricity market are derived for both the fixed and variable demand cases. The replicator dynamics stability analysis is also performed. The dynamics of the electricity markets are the results of players' decisions. The physical parameters of the power systems (such as the lines capacities, voltage limitations, etc.) also affect the market dynamics indirectly, through the changes in players' behaviors. Assuming rational players, an optimal bidding strategy for constructing the supply function (SF) of a generating firm is presented and based on that, the dynamics of the bid replicators are studied. Both fixed demands and price sensitive demands are taken into account. The replicator model is presented in the well-known state space structure. A case study is presented to show the applicability of the developed dynamic replicator bid model, and also to show how the Nash-SFE equilibrium evolves over time. (author)

  18. RISIKO INVESTASI, BID-ASK SPREAD, DAN COST OF EQUITY CAPITAL DI PASAR MODAL INDONESIA

    Directory of Open Access Journals (Sweden)

    Agus Haryono

    2017-03-01

    Full Text Available A number of studies investigated how financial information affected investment decisions. The study extendedthis line of research by examining the effect of risk, proxied by price per share, number of shareholders, numberof dealers, trading volume, accounting risk and market risk measures on the bid ask spread. Further, theresearch tried to test the relationship between bid ask spread and cost of equity capital. The samples of thisresearch were the manufacturing companies listed at Indonesian Stock Exchange which shared the dividendfor 3 years; there were 40 companies. Data analysis technique used multiple regression analysis. The results ofregression provided evidence of statistically significant effect of price per share, market value, asset size andprice variability on bid ask spread. At last, there was a positive relationship between bid ask spread and cost ofequity capital

  19. Modeling bidding competitiveness and position performance in multi-attribute construction auctions

    Directory of Open Access Journals (Sweden)

    Pablo Ballesteros-Pérez

    2015-12-01

    This paper details a practical methodology based on simple statistical calculations for modeling the performance of a single bidder or a group of bidders, constituting a useful resource for analyzing one’s own success while benchmarking potential bidding competitors.

  20. 36 CFR 223.86 - Bid restriction on resale of noncompleted contract.

    Science.gov (United States)

    2010-07-01

    ... AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER Timber Sale Contracts Advertisement and Bids... business entity or the successor in interest of any of the foregoing business entities. A person is an...

  1. 78 FR 18527 - Implementation of Competitive Bidding for Commercial Broadcast and Instructional Television Fixed...

    Science.gov (United States)

    2013-03-27

    ... Broadcast and Instructional Television Fixed Service Licenses AGENCY: Federal Communications Commission... Implementation of Competitive Bidding for Commercial Broadcast and Instructional Television Fixed Service... for Commercial Broadcast and Instructional Television Fixed Service Licenses, MM Docket No. 97- 234 et...

  2. Empirical observations of bidding patterns in Australia's National Electricity Market

    International Nuclear Information System (INIS)

    Hu Xinmin; Grozev, George; Batten, David

    2005-01-01

    For more than a decade, electricity industries have been undergoing reform worldwide. However, there are various, sometimes contradictory, conclusions about the performance of these restructured electricity markets. Market performance depends largely on how each market participant responds to the market design -- including market rules, market operational procedures, and information revelation. In this paper, we identify and examine the strategies adopted by generators in Australia's National Electricity Market, based on publicly available data for the period from May 1, 2002 to May 31, 2003. We try to understand and answer some basic questions like how generators respond collectively or individually to changes in market conditions (e.g. load changes) and why they behave in this way. The statistics calculated from the data show that wide variations in the frequency of strategic bidding and rebidding exist; that generators more frequently use capacity offers as a strategic tool than price offers; that large generating units are more likely to use capacity strategies to control market prices; and that generators are capable of responding to changes in market conditions

  3. Empirical observations of bidding patterns in Australia's National Electricity Market

    International Nuclear Information System (INIS)

    Xinmin Hu; Grozev, G.; Batten, D.

    2005-01-01

    For more than a decade, electricity industries have been undergoing reform worldwide. However, there are various, sometimes contradictory, conclusions about the performance of these restructured electricity markets. Market performance depends largely on how each market participant responds to the market design - including market rules, market operational procedures, and information revelation. In this paper, we identify and examine the strategies adopted by generators in Australia's National Electricity Market, based on publicly available data for the period from May 1, 2002 to May 31, 2003. We try to understand and answer some basic questions like how generators respond collectively or individually to changes in market conditions (e.g. load changes) and why they behave in this way. The statistics calculated from the data show that wide variations in the frequency of strategic bidding and rebidding exist; that generators more frequently use capacity offers as a strategic tool than price offers; that large generating units are more likely to use capacity strategies to control market prices; and that generators are capable of responding to changes in market conditions. (author)

  4. The Benefits and Risks of Virtual Bidding in Multi-Settlement Markets

    International Nuclear Information System (INIS)

    Isemonger, Alan G.

    2006-01-01

    While it is possible that multi-settlement markets can exist without virtual trading, it is equally clear that virtual trading can provide many market benefits. The main one: In the absence of explicit virtual bidding (EVB), the price arbitrage trades that are benign in other commodity markets affect the reliability of the underlying electricity markets, resulting in a situation where EVB is most useful when it neutralizes the deleterious reliability effects of implicit virtual bidding and physical arbitrage. (author)

  5. 30 CFR 285.224 - What happens if MMS accepts my bid?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What happens if MMS accepts my bid? 285.224... Renewable Energy Leases Competitive Lease Award Process § 285.224 What happens if MMS accepts my bid? If we... withdraw an OCS area in which we have held a lease sale before you and MMS execute the lease in that area...

  6. Refinancing, debt for equity agreements and takeover bids under Spanish law

    OpenAIRE

    Arias Varona, Francisco Javier

    2011-01-01

    This paper focuses on the connection between agreed solutions to the insolvency of listed companies implying changes in corporate control and the rules governing takeover bids. The solution to insolvency problems sometimes leads to a change in corporate control, namely when the solution involves modifying the capital structure of the company. In such cases, when the insolvent entity is a listed company, takeover bid regulation must be taken into account, as it can render the operation impossi...

  7. The 2003 proposal for a directive on Takeover Bids - Impact on the regulation in Scandinavia

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2003-01-01

    The article analysis the exspected impact of the proposed directive on takeover bids in Denmark, Norway and Sweden. The article focus on the impact on the duties of managers and of the 'mini breack-through rule'.......The article analysis the exspected impact of the proposed directive on takeover bids in Denmark, Norway and Sweden. The article focus on the impact on the duties of managers and of the 'mini breack-through rule'....

  8. Current Practices to Decrease Subcontractor Bid Shopping in the Public Sector

    Science.gov (United States)

    1993-01-01

    rarely done because most contractors refuse to accept such a condition (6s15). Those public agencies adhering to the doctrine of promissory estoppel ...also encourage bid shopping. The doctrine of promissory estoppel dictates that a subcontractor must stand by his bid quote if it is used by the prime...Holman was not awarded the subcontract. (3) It is unfair to bind the subcontractor under promissory estoppel without binding the general contractor. (4

  9. Optimal bidding strategies in oligopoly markets considering bilateral contracts and transmission constraints

    Energy Technology Data Exchange (ETDEWEB)

    A.Badri; Jadid, S. [Department of Electrical Engineering, Iran University of Science and Technology (Iran); Rashidinejad, M. [Shahid Bahonar University, Kerman (Iran); Moghaddam, M.P. [Tarbiat Modarres University, Tehran (Iran)

    2008-06-15

    In electricity industry with transmission constraints and limited number of producers, Generation Companies (GenCos) are facing an oligopoly market rather than a perfect competition one. Under oligopoly market environment, each GenCo may increase its own profit through a favorable bidding strategy. This paper investigates the problem of developing optimal bidding strategies of GenCos, considering bilateral contracts and transmission constraints. The problem is modeled with a bi-level optimization algorithm, where in the first level each GenCo maximizes its payoff and in the second level a system dispatch will be accomplished through an OPF problem in which transmission constraints are taken into account. It is assumed that each GenCo has information about initial bidding strategies of other competitors. Impacts of exercising market power due to transmission constraints as well as irrational biddings of the some generators are studied and the interactions of different bidding strategies on participants' corresponding payoffs are presented. Furthermore, a risk management-based method to obtain GenCos' optimal bilateral contracts is proposed and the impacts of these contracts on GenCos' optimal biddings and obtained payoffs are investigated. At the end, IEEE 30-bus test system is used for the case study in order to demonstrate the simulation results and support the effectiveness of the proposed model. (author)

  10. BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods.

    Directory of Open Access Journals (Sweden)

    Krzysztof J Gorgolewski

    2017-03-01

    Full Text Available The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS. The portability of these applications (BIDS Apps is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

  11. Research on Power Producer’s Bidding Behavior Based on the Best-Response Dynamic Model

    Directory of Open Access Journals (Sweden)

    Jingqi Sun

    2014-01-01

    Full Text Available As China’s electricity market is facing many problems, the research on power producer’s bidding behavior can promote the healthy and sustainable development of China’s electricity market. As a special commodity, the “electricity” possesses complicated production process. The instable market constraint condition, nonsymmetric information, and a lot of random factors make the producer’s bidding process more complex. Best-response dynamic is one of the classic dynamic mechanisms of the evolutionary game theory, which applies well in the repeated game and strategy evolution that happen among a few bounded rational players with a quick learning capability. The best-response dynamic mechanism is employed to study the power producer’s bidding behavior in this paper, the producer’s best-response dynamic model is constructed, and how the producers would engage in bidding is analyzed in detail. Taking two generating units in South China regional electricity market as the example, the producer’s bidding behavior by following the producer’s best-response dynamic model is verified. The relationships between the evolutionarily stable strategy (ESS of power producer’s bidding and the market demand, and ceiling and floor price as well as biding frequency are discussed in detail.

  12. A matrix game model for analyzing FTR bidding strategies in deregulated electric power markets

    International Nuclear Information System (INIS)

    Das, Tapas K.; Rocha, Patricio; Babayigit, Cihan

    2010-01-01

    Suppliers in deregulated electric power markets compete for financial transmission rights (FTRs) to hedge against congestion charges. The system operator receives the bids for FTRs submitted by the suppliers and develops an allocation strategy by solving an optimization model. Each FTR bid is defined by a path, a quantity indicating the amount of FTRs the supplier is bidding for in that path, and the price that the supplier is willing to pay for each FTR. The FTR revenue is calculated only after the electricity market has been cleared by computing the differences in the LMPs at the pair of nodes that connect each path. Thus, suppliers rely on forecasts of locational marginal prices (LMPs) to develop their FTR bids. In this paper, we present a game theoretic modeling approach to develop FTR bidding strategies for power suppliers assuming that they have forecasts of LMPs. The game theoretic model considers multiple participants as well as network contingencies. We apply the game theoretic model on a sample network to assess impacts of variations of bid and network parameters on the FTR market outcome. (author)

  13. Optimal bidding strategies in oligopoly markets considering bilateral contracts and transmission constraints

    International Nuclear Information System (INIS)

    Badri, A.; Jadid, S.; Rashidinejad, M.; Moghaddam, M.P.

    2008-01-01

    In electricity industry with transmission constraints and limited number of producers, Generation Companies (GenCos) are facing an oligopoly market rather than a perfect competition one. Under oligopoly market environment, each GenCo may increase its own profit through a favorable bidding strategy. This paper investigates the problem of developing optimal bidding strategies of GenCos, considering bilateral contracts and transmission constraints. The problem is modeled with a bi-level optimization algorithm, where in the first level each GenCo maximizes its payoff and in the second level a system dispatch will be accomplished through an OPF problem in which transmission constraints are taken into account. It is assumed that each GenCo has information about initial bidding strategies of other competitors. Impacts of exercising market power due to transmission constraints as well as irrational biddings of the some generators are studied and the interactions of different bidding strategies on participants' corresponding payoffs are presented. Furthermore, a risk management-based method to obtain GenCos' optimal bilateral contracts is proposed and the impacts of these contracts on GenCos' optimal biddings and obtained payoffs are investigated. At the end, IEEE 30-bus test system is used for the case study in order to demonstrate the simulation results and support the effectiveness of the proposed model. (author)

  14. Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells

    International Nuclear Information System (INIS)

    Hoshino, S.; Oshimi, K.; Tsudo, M.; Miyasaka, M.; Teramura, M.; Masuda, M.; Motoji, T.; Mizoguchi, H.

    1990-01-01

    We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody, designated Mik-beta 1. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis

  15. Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility

    Science.gov (United States)

    Meyer, Stefan; Ravandi-Kashani, Farhad; Borthakur, Gautam; Coombes, Kevin R.; Zhang, Nianxiang; Kornblau, Steven

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogenous disease with differential oncogene association, outcome and treatment regimens. Treatment strategies for AML have improved outcome but despite increased molecular biological information AML is still associated with poor prognosis. Proteomic analysis on the effects of a range of leukemogenic oncogenes showed that the protein transglutaminase 2 (TG2) is expressed at greater levels as a consequence of oncogenic transformation. Further analysis of this observation was performed with 511 AML samples using reverse phase proteomic arrays, demonstrating that TG2 expression was higher at relapse than diagnosis in many cases. In addition elevated TG2 expression correlated with increased expression of numerous adhesion proteins and many apoptosis regulating proteins, two processes related to leukemogenesis. TG2 has previously been linked to drug resistance in cancer and given the negative correlation between TG2 levels and peripheral blasts observed increased TG2 levels may lead to the protection of the leukemic stem cell due to increased adhesion/reduced motility. TG2 may therefore form part of a network of proteins that define poor outcome in AML patients and potentially offer a target to sensitize AML stem cells to drug treatment. PMID:23576428

  16. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Xueqing Jiang

    Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

  17. The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

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    Giulia Cheloni

    2017-01-01

    Full Text Available Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC. The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN are placed in tissue areas at the lower end of this range (“hypoxic” SCN, to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.

  18. Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β-Hairpin Antimicrobial Peptides.

    Science.gov (United States)

    Buri, Marcus V; Torquato, Heron F Vieira; Barros, Carlos Castilho; Ide, Jaime S; Miranda, Antonio; Paredes-Gamero, Edgar J

    2017-07-01

    Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four β-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Myeloperoxidase mRNA detection for lineage determination of leukemic blasts: retrospective analysis.

    Science.gov (United States)

    Crisan, D; Anstett, M J

    1995-07-01

    Myeloperoxidase (MPO) mRNA is an early myeloid marker; its detection in the morphologically and immunophenotypically primitive blasts of acute undifferentiated leukemia (AUL) establishes myeloid lineage and allows reclassification as acute myelogenous leukemia with minimal differentiation (AML-MO). We have previously reported a procedure for MPO mRNA detection by RT-PCR (reverse transcription-polymerase chain reaction) and an adaptation for use of routine hematology smears. This variant procedure allows retrospective analysis of mRNA and is used in the present study to evaluate the lineage of leukemic blasts in seven cases with morphology and cytochemistry consistent with AUL. All hematology smears used in this study were air-dried, unstained or Wright-stained and stored at room temperature for periods varying between 3 days and 2 years. MPO mRNA was detected in six cases, establishing the myeloid lineage of the blasts and the diagnosis of AML-MO. In the remaining case, the blasts were MPO mRNA negative, confirming the diagnosis of AUL. The RT-PCR procedure for retrospective mRNA analysis is useful in the clinical setting, due to its high specificity and sensitivity, speed (less than 24 h), safety (no radioactivity) and convenient use of routine hematology smears; it is particularly attractive in clinical situations when fresh or frozen specimens are no longer available at the time when the need for molecular diagnostics becomes apparent.

  20. Colloidal silver nanoparticles improve anti-leukemic drug efficacy via amplification of oxidative stress.

    Science.gov (United States)

    Guo, Dawei; Zhang, Junren; Huang, Zhihai; Jiang, Shanxiang; Gu, Ning

    2015-02-01

    Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy. Copyright © 2015. Published by Elsevier B.V.

  1. IMPROVING THE BIDS EVALUATION CRITERIA AND REDUCING TIME AND EFFORT OF THE ASSESSMENT BY DEVELOPING A SOFTWARE PROGRAM

    Directory of Open Access Journals (Sweden)

    Muaid A. Shhatha

    2018-05-01

    Full Text Available A number of studies have been conducted to specify the most effecting factors on the success of projects. Those studies titled the most influencing factor, which is the bid selection criterion. By this criterion, the most qualified bidder/contractor could be chosen where the contractor has a considerable impact upon projects successes. Moreover, the published studies helped a lot in correcting the improper adopted criterion in selecting the best bid, which is the lowest price bid. Awarding the bid depending on the lowest price bid ended many projects in failure. Therefore, this study aimed to revise the popular mistaken selection criterion, recommend an evaluation criterion, and develop a computer program that works on finding the best bid according to the recommended criterion. The suggested criterion was followed in selecting one of the contractors to construct some projects in Iraq. That projects were felicitously finished; the projects were completed on time and budget.

  2. Susceptibility of Hep3B cells in different phases of cell cycle to tBid.

    Science.gov (United States)

    Ma, Shi-Hong; Chen, George G; Ye, Caiguo; Leung, Billy C S; Ho, Rocky L K; Lai, Paul B S

    2011-01-01

    tBid is a pro-apoptotic molecule. Apoptosis inducers usually act in a cell cycle-specific fashion. The aim of this study was to elucidate whether effect of tBid on hepatocellular carcinoma (HCC) Hep3B cells was cell cycle phase specific. We synchronized Hep3B cells at G0/G1, S or G2/M phases by chemicals or flow sorting and tested the susceptibility of the cells to recombinant tBid. Cell viability was measured by MTT assay and apoptosis by TUNEL. The results revealed that tBid primarily targeted the cells at G0/G1 phase of cell cycle, and it also increased the cells at the G2/M phase. 5-Fluorouracil (5-FU), on the other hand, arrested Hep3B cells at the G0/G1 phase, but significantly reduced cells at G2/M phase. The levels of cell cycle-related proteins and caspases were altered in line with the change in the cell cycle. The combination of tBid with 5-FU caused more cells to be apoptotic than either agent alone. Therefore, the complementary effect of tBid and 5-FU on different phases of the cell cycle may explain their synergistric effect on Hep3B cells. The elucidation of the phase-specific effect of tBid points to a possible therapeutic option that combines different phase specific agents to overcome resistance of HCC. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Interaction between the immune system and acute myeloid leukemia: A model incorporating promotion of regulatory T cell expansion by leukemic cells.

    Science.gov (United States)

    Nishiyama, Yoshiaki; Saikawa, Yutaka; Nishiyama, Nobuaki

    2018-03-01

    Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes. The model includes promotion of Treg expansion by leukemic blast cells, leukemic stem cell and progenitor cell targeting by Teff, and Treg-mediated Teff suppression, and exhibits two coexisting, stable steady states, corresponding to high leukemic cell load at diagnosis or relapse, and to long-term complete remission. Our model is capable of explaining the clinical findings that the survival of patients with AML after allogeneic stem cell transplantation is influenced by the duration of complete remission, and that cut-off minimal residual disease thresholds associated with a 100% relapse rate are identified in AML. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture.

    Science.gov (United States)

    Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y

    1992-05-01

    We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

  5. Adhesion molecule profiles of B-cell non-Hodgkin's lymphomas in the leukemic phase

    Directory of Open Access Journals (Sweden)

    D.M. Matos

    2006-10-01

    Full Text Available We evaluated the expression of 10 adhesion molecules on peripheral blood tumor cells of 17 patients with chronic lymphocytic leukemia, 17 with mantle-cell lymphoma, and 13 with nodal or splenic marginal B-cell lymphoma, all in the leukemic phase and before the beginning of any therapy. The diagnosis of B-cell non-Hodgkin's lymphomas was based on cytological, histological, immunophenotypic, and molecular biology methods. The mean fluorescence intensity of the adhesion molecules in tumor cells was measured by flow cytometry of CD19-positive cells and differed amongst the types of lymphomas. Comparison of chronic lymphocytic leukemia and mantle-cell lymphoma showed that the former presented a higher expression of CD11c and CD49c, and a lower expression of CD11b and CD49d adhesion molecules. Comparison of chronic lymphocytic leukemia and marginal B-cell lymphoma showed that the former presented a higher expression of CD49c and a lower expression of CD11a, CD11b, CD18, CD49d, CD29, and CD54. Finally, comparison of mantle-cell lymphoma and marginal B-cell lymphoma showed that marginal B-cell lymphoma had a higher expression of CD11a, CD11c, CD18, CD29, and CD54. Thus, the CD49c/CD49d pair consistently demonstrated a distinct pattern of expression in chronic lymphocytic leukemia compared with mantle-cell lymphoma and marginal B-cell lymphoma, which could be helpful for the differential diagnosis. Moreover, the distinct profiles of adhesion molecules in these diseases may be responsible for their different capacities to invade the blood stream.

  6. Expression of MICA, MICB and NKG2D in human leukemic myelomonocytic and cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Mendoza-Rincon Jorge

    2011-04-01

    Full Text Available Abstract Background Cancer cells are known to secrete the stress molecules MICA and MICB that activate cytotoxicity by lymphocytes and NK cells through their NKG2D receptor as a mechanism of immunological defense. This work was undertaken to evaluate if cancer cells can also express this receptor as a possible mechanisms of depletion of MIC molecules and thus interfere with their immune recognition. Methods Myelomonocytic leukemic (TPH-1 and U-937 and cervical cancer (CALO and INBL cell lines were evaluated by Western Blot, ELISA, flow cytometry and immunocytochemistry to evaluate their capacity to express and secrete MICA and MICB and to be induced to proliferate by these molecules as well as to express their receptor NKG2D. Statistical analysis was performed by two-way ANOVA for time course analysis and Student's t-test for comparison between groups. Values were considered significantly different if p Results THP-1 and U-937 produce and secrete the stress MICA and MICB as shown by Western Blot of lysed cells and by ELISA of their conditioned media. By Western Blot and flow cytometry we found that these cells also express the receptor NKG2D. When THP-1 and U-937 were cultured with recombinant MICA and MICB they exhibited a dose dependent induction for their proliferation. CALO and INBL also produce MICA and MICB and were induced to proliferate by these stress molecules. By Western Blot, flow cytometry and immunocytochemistry we also found that these cells express NKG2D. Conclusions Our novel results that tumor cells can simultaneously secrete MIC molecules and express their receptor, and to be induced for proliferation by these stress molecules, and that tumor epithelial cells can also express the NKG2D receptor that was thought to be exclusive of NK and cytotoxic lymphocytes is discussed as a possible mechanism of immunological escape and of tumor growth induction.

  7. Uptake of cerium oxide nanoparticles and its influence on functions of mouse leukemic monocyte macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangyan; Wang, Bing; Jiang, Pengfei; Chen, Yiqi; Mao, Zhengwei, E-mail: zwmao@zju.edu.cn; Gao, Changyou [Zhejiang University, MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering (China)

    2015-01-15

    Exposure of the CeO{sub 2} nanoparticles (NPs) causes a public concern on their potential health risk due to their wide applications in the fields of fuel additive, commodities, pharmaceutical, and other industries. In this study, the interactions between two commercial CeO{sub 2} NPs (D-CeO{sub 2} from Degussa and PC-CeO{sub 2} from PlasmaChem) and mouse leukemic monocyte macrophage Raw264.7 cells were investigated to provide a fast and in-depth understanding of the biological influences of the NPs. Both types of the CeO{sub 2} NPs had a negative surface charge around −12 mV and showed a tendency to form aggregates with sizes of 191 ± 5.9 and 60.9 ± 2.8 nm in cell culture environment, respectively. The cellular uptake of the CeO{sub 2} NPs increased along with the increase of feeding dosage and prolongation of the culture time. The PC-CeO{sub 2} NPs had a faster uptake rate and reached higher cellular loading amount at the highest feeding concentration (200 µg/mL). In general, both types of the CeO{sub 2} NPs had rather small cytotoxicity even with a dosage as high as 200 µg/mL. The D-CeO{sub 2} NPs showed a relative stronger cytotoxicity especially at higher concentrations and longer incubation time. The NPs were dispersed in vacuoles (most likely endosomes and lysosomes) and cytoplasm. Although both types of the CeO{sub 2} NPs could suppress the production of reactive oxygen species, they impaired the mitochondria membrane potential to some extent. The cytoskeleton organization was altered and consequently the cell adhesion ability decreased after uptake of both types of the CeO{sub 2} NPs.

  8. Rapid Treatment of Leukostasis in Leukemic Mantle Cell Lymphoma Using Therapeutic Leukapheresis: A Case Report

    Directory of Open Access Journals (Sweden)

    Xuan Duc Nguyen

    2011-01-01

    Full Text Available We describe a case of severe leukocytosis caused by leukemic mantle cell lymphoma (MCL, complicated by leukostasis with myocardial infarction in which leukapheresis was used in the initial management. A 73-year-old male presented to the emergency department because of fatigue and thoracic pain. Blood count revealed 630 × 109/L WBC (white blood cells. The electrocardiogram showed ST-elevation with an increase of troponin and creatinine kinase. The diagnosis was ST-elevation myocardial infarction (STEMI induced and complicated by leukostasis. Immunophenotyping, morphology, cytogenetic and fluorescence-in-situ-hybridization analysis revealed the diagnosis of a blastoid variant of MCL. To remove leukocytes rapidly, leukapheresis was performed in the intensive care unit. Based on the differential blood count with 95% blasts, which were assigned to the lymphocyte population by the automatic hematology analyzer, leukapheresis procedures were then performed with the mononuclear cell standard program on the Spectra cell separator. The patient was treated with daily leukapheresis for 3 days. The WBC count decreased to 174 × 109/L after the third leukapheresis, with a 72% reduction. After the second apheresis, treatment with vincristine, cyclophosphamide, and prednisolone was started. The patient fully recovered in the further course of the treatment. To the best of our knowledge, this is the first report on blastoid MCL with leukostasis associated with a STEMI that was successfully treated by leukapheresis. Effective harvest of circulating lymphoma cells by leukapheresis requires adaptation of instrument settings based on the results of the differential blood count prior to apheresis.

  9. Long Terminal Repeat CRISPR-CAR-Coupled "Universal" T Cells Mediate Potent Anti-leukemic Effects.

    Science.gov (United States)

    Georgiadis, Christos; Preece, Roland; Nickolay, Lauren; Etuk, Aniekan; Petrova, Anastasia; Ladon, Dariusz; Danyi, Alexandra; Humphryes-Kirilov, Neil; Ajetunmobi, Ayokunmi; Kim, Daesik; Kim, Jin-Soo; Qasim, Waseem

    2018-03-06

    Gene editing can be used to overcome allo-recognition, which otherwise limits allogeneic T cell therapies. Initial proof-of-concept applications have included generation of such "universal" T cells expressing chimeric antigen receptors (CARs) against CD19 target antigens combined with transient expression of DNA-targeting nucleases to disrupt the T cell receptor alpha constant chain (TRAC). Although relatively efficient, transgene expression and editing effects were unlinked, yields variable, and resulting T cell populations heterogeneous, complicating dosing strategies. We describe a self-inactivating lentiviral "terminal" vector platform coupling CAR expression with CRISPR/Cas9 effects through incorporation of an sgRNA element into the ΔU3 3' long terminal repeat (LTR). Following reverse transcription and duplication of the hybrid ΔU3-sgRNA, delivery of Cas9 mRNA resulted in targeted TRAC locus cleavage and allowed the enrichment of highly homogeneous (>96%) CAR + (>99%) TCR - populations by automated magnetic separation. Molecular analyses, including NGS, WGS, and Digenome-seq, verified on-target specificity with no evidence of predicted off-target events. Robust anti-leukemic effects were demonstrated in humanized immunodeficient mice and were sustained longer than by conventional CAR + TCR + T cells. Terminal-TRAC (TT) CAR T cells offer the possibility of a pre-manufactured, non-HLA-matched CAR cell therapy and will be evaluated in phase 1 trials against B cell malignancies shortly. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. Proteoglycan biosynthesis in murine monocytic leukemic (M1) cells before and after differentiation

    International Nuclear Information System (INIS)

    McQuillan, D.J.; Yanagishita, M.; Hascall, V.C.; Bickel, M.

    1989-01-01

    Murine monocytic leukemic (M1) cells were cultured in the presence of [ 3 H]glucosamine and [ 35 S]sulfate. Labeled proteoglycans were purified by anion exchange chromatography and characterized by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with chemical and enzymatic degradation. M1 cells synthesize a single predominant species of proteoglycan which distributes almost equally between the cell and medium after 17 h labeling. The cell-associated proteoglycan has an overall size of about 135 kDa and contains three to five chondroitin sulfate chains (28-31 kDa each) attached to a chondroitinase-generated core protein of 28 kDa. The synthesis and subsequent secretion of this proteoglycan was enhanced 4-5-fold in cells induced to differentiate into macrophages. This was not a phenomenon of arrest in the G0/G1 stage of the cell cycle, since density inhibited undifferentiated cells arrested at this stage did not increase proteoglycan synthesis. The chondroitin sulfate chains contained exclusively chondroitin 4- and 6-sulfate; however, the ratio of these two disaccharides differed between the medium- and cell-associated proteoglycans, and changed during progression of the cells into a fully differentiated phenotype. Pulse-chase kinetics indicate the presence of two distinct pools of proteoglycan; one that is secreted very rapidly from the cell after a approximately 1-h lag, and a second pool that is turned over in the cell with a half-time of approximately 3.5 h. Subtle differences in the glycosylation patterns of the medium- and cell-associated species are consistent with synthesis of two pools. Papain digestion suggests that the chondroitin sulfate chains are clustered on a small protease resistant peptide. The data suggest that this proteoglycan is similar to the serglycin proteoglycan family

  11. Do endothelial cells belong to the primitive stem leukemic clone in CML? Role of extracellular vesicles.

    Science.gov (United States)

    Ramos, Teresa L; Sánchez-Abarca, Luis Ignacio; López-Ruano, Guillermo; Muntión, Sandra; Preciado, Silvia; Hernández-Ruano, Montserrat; Rosado, Belén; de las Heras, Natalia; Chillón, M Carmen; Hernández-Hernández, Ángel; González, Marcos; Sánchez-Guijo, Fermín; Del Cañizo, Consuelo

    2015-08-01

    The expression of BCR-ABL in hematopoietic stem cells is a well-defined primary event in chronic myeloid leukemia (CML). Some reports have described the presence of BCR-ABL on endothelial cells from CML patients, suggesting the origin of the disease in a primitive hemangioblastic cell. On the other hand, extracellular vesicles (EVs) released by CML leukemic cells are involved in the angiogenesis modulation process. In the current work we hypothesized that EVs released from BCR-ABL(+) cells may carry inside the oncogene that can be transferred to endothelial cells leading to the expression of both BCR-ABL transcript and the oncoprotein. EVs from K562 cells and plasma of newly diagnosed CML patients were isolated by ultracentrifugation. RT-PCR analysis detected the presence of BCR-ABL RNA in the EVs isolated from both K562 cells and plasma of CML patients. The incorporation of these EVs into endothelial cells was demonstrated by flow cytometry and fluorescence microscopy showed that after 24h of incubation most EVs were incorporated. BCR-ABL transcripts were detected in all experiments on endothelial cells incubated with EVs from both sources. The presence of BCR-ABL on endothelial cells incubated with Philadelphia(+) EVs was also confirmed by Western blot assays. In summary, endothelial cells acquire BCR-ABL RNA and the oncoprotein after incubation with EVs released from Ph(+) positive cells (either from K562 cells or from plasma of newly diagnosed CML patients). This results challenge the hypothesis that endothelial cells may be part of the Philadelphia(+) clone in CML. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Robust Multi-unit Auction Protocol against False-name Bids

    Science.gov (United States)

    Yokoo, Makoto; Sakurai, Yuko; Matsubara, Shigeo

    This paper presents a new multi-unit auction protocol (IR protocol) that is robust against false-name bids. Internet auctions have become an integral part of Electronic Commerce and a promising field for applying agent and Artificial Intelligence technologies. Although the Internet provides an excellent infrastructure for executing auctions, the possibility of a new type of cheating called false-name bids has been pointed out. A false-name bid is a bid submitted under a fictitious name. A protocol called LDS has been developed for combinatorial auctions of multiple different items and has proven to be robust against false-name bids. Although we can modify the LDS protocol to handle multi-unit auctions, in which multiple units of an identical item are auctioned, the protocol is complicated and requires the auctioneer to carefully pre-determine the combination of bundles to obtain a high social surplus or revenue. For the auctioneer, our newly developed IR protocol is easier to use than the LDS, since the combination of bundles is automatically determined in a flexible manner according to the declared evaluation values of agents. The evaluation results show that the IR protocol can obtain a better social surplus than that obtained by the LDS protocol.

  13. A Bidding Methodology by Nash Equilibrium for Finite Generators Participating in Imperfect Electricity Markets

    Science.gov (United States)

    Satyaramesh, P. V.

    2014-01-01

    This paper presents an application of finite n-person non-cooperative game theory for analyzing bidding strategies of generators in a deregulated energy marketplace with Pool Bilateral contracts so as to maximize their net profits. A new methodology to build bidding methodology for generators participating in oligopoly electricity market has been proposed in this paper. It is assumed that each generator bids a supply function. This methodology finds out the coefficients in the supply function of generators in order to maximize benefits in an environment of competing rival bidders. A natural choice for developing strategies is Nash Equilibrium (NE) model incorporating mixed strategies, for solving the bidding problem of electrical market. Associated optimal profits are evaluated for a combination of set of pure strategies of bidding of generators, and payoff matrix has been constructed. The optimal payoff is calculated by using NE. An attempt has also been made to minimize the gap between the optimal payoff and the payoff obtained by a possible mixed strategies combination. The algorithm is coded in MATLAB. A numerical example is used to illustrate the essential features of the approach and the results are proved to be the optimal values.

  14. Group search optimiser-based optimal bidding strategies with no Karush-Kuhn-Tucker optimality conditions

    Science.gov (United States)

    Yadav, Naresh Kumar; Kumar, Mukesh; Gupta, S. K.

    2017-03-01

    General strategic bidding procedure has been formulated in the literature as a bi-level searching problem, in which the offer curve tends to minimise the market clearing function and to maximise the profit. Computationally, this is complex and hence, the researchers have adopted Karush-Kuhn-Tucker (KKT) optimality conditions to transform the model into a single-level maximisation problem. However, the profit maximisation problem with KKT optimality conditions poses great challenge to the classical optimisation algorithms. The problem has become more complex after the inclusion of transmission constraints. This paper simplifies the profit maximisation problem as a minimisation function, in which the transmission constraints, the operating limits and the ISO market clearing functions are considered with no KKT optimality conditions. The derived function is solved using group search optimiser (GSO), a robust population-based optimisation algorithm. Experimental investigation is carried out on IEEE 14 as well as IEEE 30 bus systems and the performance is compared against differential evolution-based strategic bidding, genetic algorithm-based strategic bidding and particle swarm optimisation-based strategic bidding methods. The simulation results demonstrate that the obtained profit maximisation through GSO-based bidding strategies is higher than the other three methods.

  15. Quantifying fluctuations in market liquidity: analysis of the bid-ask spread.

    Science.gov (United States)

    Plerou, Vasiliki; Gopikrishnan, Parameswaran; Stanley, H Eugene

    2005-04-01

    Quantifying the statistical features of the bid-ask spread offers the possibility of understanding some aspects of market liquidity. Using quote data for the 116 most frequently traded stocks on the New York Stock Exchange over the two-year period 1994-1995, we analyze the fluctuations of the average bid-ask spread S over a time interval deltat. We find that S is characterized by a distribution that decays as a power law P[S>x] approximately x(-zeta(S) ), with an exponent zeta(S) approximately = 3 for all 116 stocks analyzed. Our analysis of the autocorrelation function of S shows long-range power-law correlations, (S(t)S(t + tau)) approximately tau(-mu(s)), similar to those previously found for the volatility. We next examine the relationship between the bid-ask spread and the volume Q, and find that S approximately ln Q; we find that a similar logarithmic relationship holds between the transaction-level bid-ask spread and the trade size. We then study the relationship between S and other indicators of market liquidity such as the frequency of trades N and the frequency of quote updates U, and find S approximately ln N and S approximately ln U. Lastly, we show that the bid-ask spread and the volatility are also related logarithmically.

  16. Facilitators and Inhibitors of Bidding and Hosting Mega Sporting Events in Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Koosha

    2013-01-01

    Full Text Available Legacies of hosting mega sporting events have been attempting idea for both the developed and the developing nations to participate in "bidding" competitions. Through mega sporting events bid process, despite all defined essentials infrastructures, the viewpoint of local organizing committee play a significant role to propose a winning bid and delivery of successful games. This research aims to identify the facilitators and inhibitors of bidding and hosting mega sporting events in Iran from the viewpoints of the Iranian distinguished professors in the sport management and the sport executive managers. Researcher questionnaire and Semi-structure interviews were conducted to gain in depth data. The results indicated that Iran currently has limitations to have winning bid and successful host mega sporting events; even though, it possesses the potential to do so. Public interest and support for hosting the sport events, good security condition against terrorism and tourist attractions are known as the strong points and he challenges and inhibitors which Iran is faced with includes: the qualitative and quantitative weakness in the transportation infrastructures and sport venues, west countries economic boycott, unstable government support and the lack of long-run planning for the events.

  17. Profound radiosensitivity in leukemic T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling

    International Nuclear Information System (INIS)

    Nakazawa, S.; Minowada, J.; Tsubota, T.; Sinks, L.F.

    1978-01-01

    Radiation sensitivity was determined by measuring spontaneous release from 51 Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases

  18. Inhibition of time-dependent enhancement of amino acid transport by leukemic leukocytes: a possible index of the sensitivity of cells to drugs

    Energy Technology Data Exchange (ETDEWEB)

    Frengley, P A; Peck, W A; Lichtman, M A

    1975-01-01

    Leukemic leukocytes increase their rates of alpha aminoisobutyric acid (AIB) accumulation when incubated for prolonged periods in amino acid deficient media. The time-dependent increase was prevented by concurrent exposure of cells to cycloheximide or actinomycin D in vitro. In addition, the increase in AIB uptake was not present in leukemic blasts studied in vitro when the cells were obtained from subjects with acute myeloblastic leukemia who had received antileukemic therapy. Cortisol added to cell suspensions in vitro inhibited the development of time-dependent increases in AIB uptake in lymphoid cells, but accentuated the process slightly in myeloblasts. Cortisol administered to a subject with CLL by infusion reduced the time-dependent increase in AIB uptake by CLL cells subsequently studied in vitro. These data indicate that the time-dependent increase in AIB uptake may be a means of testing the sensitivity of leukemic cells to drugs.

  19. Combined Treatment with Low Concentrations of Decitabine and SAHA Causes Cell Death in Leukemic Cell Lines but Not in Normal Peripheral Blood Lymphocytes

    Directory of Open Access Journals (Sweden)

    Barbora Brodská

    2013-01-01

    Full Text Available Epigenetic therapy reverting aberrant acetylation or methylation offers the possibility to target preferentially tumor cells and to preserve normal cells. Combination epigenetic therapy may further improve the effect of individual drugs. We investigated combined action of demethylating agent decitabine and histone deacetylase inhibitor SAHA (Vorinostat on different leukemic cell lines in comparison with peripheral blood lymphocytes. Large decrease of viability, as well as huge p21WAF1 induction, reactive oxygen species formation, and apoptotic features due to combined decitabine and SAHA action were detected in leukemic cell lines irrespective of their p53 status, while essentially no effect was observed in response to the combined drug action in normal peripheral blood lymphocytes of healthy donors. p53-dependent apoptotic pathway was demonstrated to participate in the wtp53 CML-T1 leukemic cell line response, while significant influence of reactive oxygen species on viability decrease has been detected in p53-null HL-60 cell line.

  20. Analisis Faktor-Faktor Yang Mempengaruhi Bid Ask Spread Pada Masa Sebelum Dan Sesudah Stock Split Di Bursa Efek Indonesia Periode 2008-2013

    OpenAIRE

    Pakpahan, Quitsyah Agnes

    2014-01-01

    Bid Ask Spread is the difference of ask-price and bid-price of shares on the capital market. Bid ask spread is a factor that can influence the investor decision whether hold or sell their shares and make profit from spread of ask price and bid price. This is indicates that the stock liquidity as reflected in the stock price, trading volume, stock return will affect bid ask spread. Bid ask spread will increase if the risk of stock is increase, such as the less liquidity of stock, the higher ri...

  1. A supply function model for representing the strategic bidding of the producers in constrained electricity markets

    International Nuclear Information System (INIS)

    Bompard, Ettore; Napoli, Roberto; Lu, Wene; Jiang, Xiuchen

    2010-01-01

    The modeling of the bidding behaviour of the producer is a key-point in the modeling and simulation of the competitive electricity markets. In our paper, the linear supply function model is applied so as to find the Supply Function Equilibrium analytically. It also proposed a new and efficient approach to find SFEs for the network constrained electricity markets by finding the best slope of the supply function with the help of changing the intercept, and the method can be applied on the large systems. The approach proposed is applied to study IEEE-118 bus test systems and the comparison between bidding slope and bidding intercept is presented, as well, with reference to the test system. (author)

  2. Pricing strategies, the strength of bidding intentions, and online auction performance: a cross-cultural study.

    Science.gov (United States)

    Peng, Yu-Shu; Jan, Lih-Tsyr

    2009-10-01

    Over the past decade, electronic markets based on the Internet, particularly online auctions, have become popular venues for conducting business. Previous studies often focused on the construction of the best bidding model, while few studies have tried to integrate multiple pricing strategies to predict the probability of closing an auction and the price premium. This study constructs a mediated model to examine the relationship among pricing strategies, the strength of bidding intentions, and online auction performance. The sample consists of 1,055 auctions of iPod MP3 players from eBay Web sites in Hong Kong, Singapore, Belgium, and France. Empirical results show that the pricing strategies directly influence both the probability of closing an auction and the level of price premium. The pricing strategies also indirectly influence the price premium through the mediating effect of the strength of bidding intentions.

  3. Market performance and bidders' bidding behavior in the New York Transmission Congestion Contract market

    International Nuclear Information System (INIS)

    Zhang, Ning

    2009-01-01

    Using publicly available bidder level bids data for Transmission Congestion Contracts (TCCs) and the realized awards of TCCs in the NYISO monthly reconfiguration auctions from June 2000 to December 2004, we examine both market performance and bidders' bidding behavior in the auctions. The data show significant under-pricing in the realized awards of TCCs. Theories suggest that under-pricing may arise from risk-aversion, monopsonistic market power or winner's curse. Our empirical analysis illustrates that all of the three effects play a role in the NYISO TCCs market. Both market performance and bidders' bidding strategies can be best explained by the theoretical model with asymmetric information and risk-averse bidders. (author)

  4. Optimal risky bidding strategy for a generating company by self-organising hierarchical particle swarm optimisation

    International Nuclear Information System (INIS)

    Boonchuay, Chanwit; Ongsakul, Weerakorn

    2011-01-01

    In this paper, an optimal risky bidding strategy for a generating company (GenCo) by self-organising hierarchical particle swarm optimisation with time-varying acceleration coefficients (SPSO-TVAC) is proposed. A significant risk index based on mean-standard deviation ratio (MSR) is maximised to provide the optimal bid prices and quantities. The Monte Carlo (MC) method is employed to simulate rivals' behaviour in competitive environment. Non-convex operating cost functions of thermal generating units and minimum up/down time constraints are taken into account. The proposed bidding strategy is implemented in a multi-hourly trading in a uniform price spot market and compared to other particle swarm optimisation (PSO). Test results indicate that the proposed SPSO-TVAC approach can provide a higher MSR than the other PSO methods. It is potentially applicable to risk management of profit variation of GenCo in spot market.

  5. Simulating GenCo bidding strategies in electricity markets with an agent-based model

    International Nuclear Information System (INIS)

    Botterud, Audun; Thimmapuram, Prakash R.; Yamakado, Malo

    2005-01-01

    In this paper we use an agent-based simulation model, EMCAS, to analyze market power in electricity markets. We focus on the effect of congestion management on the ability of generating companies (GenCos) to raise prices beyond competitive levels. An 11-node test power system is used to compare a market design based on locational marginal pricing with a market design that uses system marginal pricing and congestion management by counter trading. Bidding strategies based on both physical and economic withholding are compared to a base case with production cost bidding. The results show that unilateral market power is exercised under both pricing mechanisms. However, the largest changes in consumer costs and GenCo profits due to strategic bidding occur under the locational marginal pricing scheme. The analysis also illustrates that agent-based modeling can contribute important insights into the complex interactions between the participants in transmission-constrained electricity markets. (Author)

  6. Resource use and costs of exenatide bid or insulin in clinical practice

    DEFF Research Database (Denmark)

    Kiiskinen, Urpo; Matthaei, Stephan; Reaney, Matthew

    2013-01-01

    .9 in the exenatide bid cohort and €3265.5 in the insulin cohort (€1791.9 versus €2465.5 due to costs other than those of injectable therapy). When baseline direct cost and patients' and disease characteristics were controlled for, mean direct costs differed by country (P ...-month, prospective, noninterventional observational study. Clinical and resource use data were collected at initiation of first injectable therapy (exenatide bid or insulin) and at regular intervals for 24 months. Costs were evaluated from the national health care system perspective at 2009 prices....... RESULTS: A total of 2515 patients were recruited. At the 24-month analysis, significant treatment change had occurred during the study in 42.2% of 1114 eligible patients in the exenatide bid cohort and 36.0% of 1274 eligible patients in the insulin cohort. Improvements in glycemic control were observed...

  7. Transportation Service Procurement Bid Construction Problem from Less Than Truckload Perspective

    Directory of Open Access Journals (Sweden)

    Fang Yan

    2018-01-01

    Full Text Available This paper presents mixed integer programming for a transportation service procurement bid construction problem from a less than full truckload perspective, in which the bidders (carriers generate their best bid (package using a bundled price to maximize their utility and increase the chance of winning the business. The models are developed from both the carriers and shippers perspectives to establish a relationship between the quoted price and the likelihood of winning to assist the carriers in balancing the potential benefits and the possibility of winning the bid. An intelligent algorithm based on Particle Swarm Optimization is then designed to solve the proposed model and hypothetical data sets are used to test the effectiveness and efficiency of the proposed model and algorithm.

  8. The strategy curve. A method for representing and interpreting generator bidding strategies

    International Nuclear Information System (INIS)

    Lucas, N.; Taylor, P.

    1995-01-01

    The pool is the novel trading arrangement at the heart of the privatized electricity market in England and Wales. This central role in the new system makes it crucial that it is seen to function efficiently. Unfortunately, it is governed by a set of complex rules, which leads to a lack of transparency, and this makes monitoring of its operation difficult. This paper seeks to provide a method for illuminating one aspect of the pool, that of generator bidding behaviour. We introduce the concept of a strategy curve, which is a concise device for representing generator bidding strategies. This curve has the appealing characteristic of directly revealing any deviation in the bid price of a genset from the costs of generating electricity. After a brief discussion about what constitutes price and cost in this context we present a number of strategy curves for different days and provide some interpretation of their form, based in part on our earlier work with game theory. (author)

  9. Conjectural variation based learning model of strategic bidding in spot market

    International Nuclear Information System (INIS)

    Yiqun Song; Yixin Ni; Fushuan Wen; Wu, F.F.

    2004-01-01

    In actual electricity market, which operates repeatedly on the basis of one hour or half hour, each firm might learn or estimate other competitors' strategic behaviors from available historical market operation data, and rationally aims at its maximum profit in the repeated biddings. A conjectural variation based learning method is proposed in this paper for generation firm to improve its strategic bidding performance. In the method, each firm learns and dynamically regulates its conjecture upon the reactions of its rivals to its bidding according to available information published in the electricity market, and then makes its optimal generation decision based on the updated conjectural variation of its rivals. Through such learning process, the equilibrium reached in the market is proven a Nash equilibrium. Motivation of generation firm to learn in the changing market environment and consequence of learning behavior in the market are also discussed through computer tests. (author)

  10. BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella

    Science.gov (United States)

    Andree, Maria; Seeger, Jens M; Schüll, Stephan; Coutelle, Oliver; Wagner-Stippich, Diana; Wiegmann, Katja; Wunderlich, Claudia M; Brinkmann, Kerstin; Broxtermann, Pia; Witt, Axel; Fritsch, Melanie; Martinelli, Paola; Bielig, Harald; Lamkemeyer, Tobias; Rugarli, Elena I; Kaufmann, Thomas; Sterner-Kock, Anja; Wunderlich, F Thomas; Villunger, Andreas; Martins, L Miguel; Krönke, Martin; Kufer, Thomas A; Utermöhlen, Olaf; Kashkar, Hamid

    2014-01-01

    The X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti-apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase-mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP-mediated immune response by inducing the BID-dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain-dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization. PMID:25056906

  11. Supplier bidding strategy based on non-cooperative game theory concepts in single auction power pools

    International Nuclear Information System (INIS)

    Kang, Dong-Joo; Kim, Balho H.; Hur, Don

    2007-01-01

    In single auction power pools, only generators bid several energy price segments depending on the amount of energy supply, at individual generating companies' (GENCO) own discretion, for every trading interval. Then all selected bidders are paid a uniform Market Clearing Price (MCP). In this paper, it is realized that each GENCO has the complete information on its own payoff as well as the other parties' payoffs, corresponding to each potential combination of choices of strategies by all the players. Specifically, all the suppliers attempt to estimate the others' bids using the concept of Nash equilibrium in the general sense of profit maximization. Under some simplified assumptions, this problem can be modeled as a simultaneous-move game confronted by the bidders. Here, the system demand forecast by competitive sellers is captured for the purpose of constructing the optimal bidding strategy. Finally, a numerical example is presented demonstrating the effectiveness of the proposed solution scheme. (author)

  12. A Sequence Mining Method to Predict the Bidding Strategy of Trading Agents

    Science.gov (United States)

    Nikolaidou, Vivia; Mitkas, Pericles A.

    In this work, we describe the process used in order to predict the bidding strategy of trading agents. This was done in the context of the Reverse TAC, or CAT, game of the Trading Agent Competition. In this game, a set of trading agents, buyers or sellers, are provided by the server and they trade their goods in one of the markets operated by the competing agents. Better knowledge of the strategy of the trading agents will allow a market maker to adapt its incentives and attract more agents to its own market. Our prediction was based on the time series of the traders’ past bids, taking into account the variation of each bid compared to its history. The results proved to be of satisfactory accuracy, both in the game’s context and when compared to other existing approaches.

  13. A new quantum sealed-bid auction protocol with secret order in post-confirmation

    Science.gov (United States)

    Wang, Jing-Tao; Chen, Xiu-Bo; Xu, Gang; Meng, Xiang-Hua; Yang, Yi-Xian

    2015-10-01

    A new security protocol for quantum sealed-bid auction is proposed to resist the collusion attack from some malicious bidders. The most significant feature of this protocol is that bidders prepare their particles with secret order in post-confirmation for encoding bids. In addition, a new theorem and its proof are given based on the theory of combinatorial mathematics, which can be used as evaluation criteria for the collusion attack. It is shown that the new protocol is immune to the collusion attack and meets the demand for a secure auction. Compared with those previous protocols, the security, efficiency and availability of the proposed protocol are largely improved.

  14. Alkaloid-rich fraction of Himatanthus lancifolius contains anti-tumor agents against leukemic cells

    Directory of Open Access Journals (Sweden)

    Melissa Pires de Lima

    2010-06-01

    Full Text Available The effects of the alkaloid-rich fraction of Himatanthus lancifolius (Müll. Arg Woodson on normal marrow cells and leukemic cell lines were investigated. After 48 h exposure, the proliferation assay showed significant cell growth inhibition for Daudi (0.1-10 µg/mL, K-562 (1-10 µg/mL, and REH cells (10-100 µg/mL, yet was inert for normal marrow cells. A similar inhibition profile was observed in clonogenic assays. This alkaloid-rich fraction, in which uleine is the main compound, showed no signs of toxicity to any cells up to 10 µg/mL. Cell feature analyses after induction of differentiation showed maintenance of the initial phenotype. Flow cytometric expression of Annexin-V and 7-AAD in K-562 and Daudi cells has indicated that the cells were not undergoing apoptosis or necrosis, suggesting cytostatic activity for tumor cellsOs efeitos da fração rica em alcalóides indólicos de Himatanthus lancifolius (Müll. Arg Woodson sobre células normais de medula óssea e linhagens celulares leucêmicas foram investigados. Após 48 horas de exposição, os ensaios de proliferação demonstraram efeitos inibitórios significativos para as linhagens Daudi (0,1-10 µg/mL, K-562 (1-10 µg/mL e REH (10-100 µg/mL, enquanto mostrou-se inerte sobre células normais de medula óssea. Os perfis de inibição se repetiram nos ensaios clonogênicos. A fração rica em alcalóides, na qual a uleína é a substância majoritária, não demonstrou toxicidade até a dose de 10 µg/mL para nenhuma das células incluídas no estudo. Da mesma forma, não se observou influência dessa fração sobre a diferenciação celular dessas linhagens, mas manutenção de seu estado maturacional inicial. O conjunto de dados descritos associado à baixa co-expressão de anexina-V e 7-AAD sugerem que esta fração exerce atividade citostática para células tumorais.

  15. Evaluation of reliability on STR typing at leukemic patients used for forensic purposes.

    Science.gov (United States)

    Filoglu, G; Bulbul, O; Rayimoglu, G; Yediay, F E; Zorlu, T; Ongoren, S; Altuncul, H

    2014-06-01

    Over the past decades, main advances in the field of molecular biology, coupled with benefits in genomic technologies, have led to detailed molecular investigations in the genetic diversity generated by researchers. Short tandem repeat (STR) loci are polymorphic loci found throughout all eukaryotic genome. DNA profiling identification, parental testing and kinship analysis by analysis of STR loci have been widely used in forensic sciences since 1993. Malignant tissues may sometimes be the source of biological material for forensic analysis, including identification of individuals or paternity testing. There are a number of studies on microsatellite instability in different types of tumors by comparing the STR profiles of malignant and healthy tissues on the same individuals. Defects in DNA repair pathways (non-repair or mis-repair) and metabolism lead to an accumulation of microsatellite alterations in genomic DNA of various cancer types that result genomic instabilities on forensic analyses. Common forms of genomic instability are loss of heterozygosity (LOH) and microsatellite instability (MSI). In this study, the applicability of autosomal STR markers, which are routinely used in forensic analysis, were investigated in order to detect genotypes in blood samples collected from leukemic patients to estimate the reliability of the results when malignant tissues are used as a source of forensic individual identification. Specimens were collected from 90 acute and 10 chronic leukemia volunteers with oral swabs as well as their paired peripheral blood samples from the Oncology Centre of the Department of Hematology at Istanbul University, during the years 2010-2011. Specimens were tested and compared with 16 somatic STR loci (CSFIPO, THO1, TPOX, vWA, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11 and FGA) widely used in forensic identification and kinship. Only two STR instabilities were encountered among 100 specimens. An MSI in

  16. Clinical approach to circumvention of multidrug resistance in refractory leukemic patients: association of cyclosporin A with etoposide.

    Science.gov (United States)

    Maia, R C; Carriço, M K; Klumb, C E; Noronha, H; Coelho, A M; Vasconcelos, F C; Ruimanek, V M

    1997-12-01

    Alternative therapy for refractory leukemic patients is being increasingly adopted. Circumvention of multidrug resistance represents a strategy that has been taken into account when conventional chemotherapy failed. In this work a group of 15 refractory, heavily pretreated, patients was enrolled in a circumvention protocol including etoposide (ETO) and cyclosporin A (CSA). All patients received etoposide prior to this schedule. Toxicity to circumvention protocol was acceptable and only one serious side-effect was observed. Two hematological clinical responses were seen, both of which were positive to P-glycoprotein immunostaining and exhibited in vitro modulation by CSA in cultures using the thymidine incorporation assay. Three out of four patients negative for P-glycoprotein achieved a minor response. Three out of six clinical failures were also negative for Pgp immunostaining one of which exhibited sinergistic effect between ETO and CSA. Our study suggests that hematological response to ETO and CSA association can be obtained in intensely pretreated leukemic patients. Several factors may affect the response such as clinical status before this therapy. Additionally, it also suggests that not all CSA effects on the combination ETO-CSA can be attributed to Pgp modulation.

  17. Human Leukemic Cells performing Oxidative Phosphorylation (OXPHOS Generate an Antioxidant Response Independently of Reactive Oxygen species (ROS Production

    Directory of Open Access Journals (Sweden)

    Abrar Ul Haq Khan

    2016-01-01

    Full Text Available Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS generate reactive oxygen species (ROS through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE, e.g. the genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 and releases NRF2, which activates AREs. We show in vitro and in vivo that OXPHOS induces, both in primary leukemic cells and cell lines, de novo expression of NQO-1 and HO-1 and also the MAPK ERK5 and decreases KEAP1 mRNA. ERK5 activates the transcription factor MEF2, which binds to the promoter of the miR-23a–27a–24-2 cluster. Newly generated miR-23a destabilizes KEAP1 mRNA by binding to its 3′UTR. Lower KEAP1 levels increase the basal expression of the NRF2-dependent genes NQO-1 and HO-1. Hence, leukemic cells performing OXPHOS, independently of de novo ROS production, generate an antioxidant response to protect themselves from ROS.

  18. NO-donating aspirin inhibits the growth of leukemic Jurkat cells and modulates β-catenin expression

    International Nuclear Information System (INIS)

    Nath, Niharika; Labaze, Georges; Rigas, Basil; Kashfi, Khosrow

    2004-01-01

    β-Catenin has been implicated in leukemic cell proliferation. We compared the effects of aspirin (ASA) and the ortho, meta, and para positional isomers of NO-donating aspirin (NO-ASA) on cell growth and β-catenin expression in human Jurkat T leukemic cells. Cell growth inhibition was strong: IC 50 for p-, o-, and m- were 20 ± 1.6 (mean ± SEM), 15 ± 1.5, and 200 ± 12 μM, respectively, in contrast to that of ASA (3200 ± 375 μM). The para isomer of NO-ASA degraded β-catenin in a dose- and time-dependent manner coinciding with increasing expression of activated caspase-3. The caspase inhibitor ZVAD blocked β-catenin cleavage by p-NO-ASA and partially reversed cell growth inhibition by p-NO-ASA but not that by ASA. A denitrated analog of p-NO-ASA did not degrade β-catenin indicating the importance of the NO-donating moiety. Our findings suggest that NO-ASA merits further study as an agent against leukemia

  19. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

    International Nuclear Information System (INIS)

    Santos, Nuno R. dos; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T.

    2010-01-01

    Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL

  20. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Nuno R. dos, E-mail: nrsantos@ualg.pt; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T. [IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2010-11-05

    Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.

  1. TRIM32 promotes retinoic acid receptor α-mediated differentiation in human promyelogenous leukemic cell line HL60

    International Nuclear Information System (INIS)

    Sato, Tomonobu; Okumura, Fumihiko; Iguchi, Akihiro; Ariga, Tadashi; Hatakeyama, Shigetsugu

    2012-01-01

    Highlights: ► TRIM32 enhanced RARα-mediated transcriptional activity even in the absence of RA. ► TRIM32 stabilized RARα in the human promyelogenous leukemic cell line HL60. ► Overexpression of TRIM32 in HL60 cells induced granulocytic differentiation. ► TRIM32 may function as a coactivator for RARα-mediated transcription in APL cells. -- Abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor α (RARα). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RARα and enhances transcriptional activity of RARα in mouse neuroblastoma cells and embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RARα, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RARα-mediated transcriptional activity even in the absence of RA and stabilizes RARα in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RARα-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.

  2. Hematopoietic stem cells can be separated from leukemic cells in a subgroup of adult acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Wang, Wenwen; Foerner, Elena; Buss, Eike; Jauch, Anna; Eckstein, Volker; Wuchter, Patrick; Ho, Anthony D; Lutz, Christoph

    2017-06-01

    In B-cell acute lymphoblastic leukemia (B-ALL) separation of normal hematopoietic stem cells (HSC) has so far been limited to a subgroup of patients. As aldehyde dehydrogenase (ALDH)-activity is enriched in various stem cells we investigated its value for HSC isolation in adult B-ALL. Based on ALDH-activity patients could be stratified in ALDH-numerous (≥1.9% ALDH +  cells) and ALDH-rare (cells) cases. In ALDH-rare B-ALL clonal-marker negative HSC could be separated by the CD34 + CD38 - ALDH +  phenotype, whereas this separation was not possible in ALDH-numerous B-ALL. Functional analysis confirmed the HSC-potential of isolated cells, which were uniformly CD19-negative. However, addition of ALDH-activity further improved HSC-purity. In summary, we provide a method to separate functionally normal HSC from leukemic cells in a subgroup of B-ALL patients that can be identified prospectively. This protocol thereby facilitates comparative analyses of matched HSC and leukemic cells in order to improve our understanding of leukemia evolution.

  3. Properties of murine leukemia viruses produced by leukemic cells established from NIH Swiss mice with radiation-induced leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Okumoto, Masaaki; Nishikawa, Ryosuke; Takamori, Yasuhiko; Iwai, Yoshiaki; Iwai, Mineko [Radiation Center of Osaka Prefecture, Sakai (Japan); Imai, Shunsuke; Morimoto, Junji; Tsubura, Yoshihiko

    1984-06-01

    Three leukemic cell lines, designated NIH-RL1, NIH-RL2 and NFS-RL1, were established from spleen and thymuses of NIH Swiss and NFS mice with radiation-induced leukemia. The culture fluids of these cell lines contained RNA-dependent DNA polymerase (RDDP) activities associated with particles of buoyant density of 1.15-1.17 (g/cm/sup 3/). The divalent cation reqirement of these enzymes was characteristic for that of murine leukemia viruses. In competition radioimmunoassay, a major core protein, p30, was detected in culture fluid of each leukemic cell line. Competition curves of viral p30 produced by these cell lines revealed that these viruses were very similar to those of xenotropic viruses of NZB mice. These viruses were undetectable both by XC plaque assay using SC-1 cells as an indicator cell, and by mink S/sup +/L/sup -/ focus induction assay. These viruses also lacked productive infectivity to mink lung cells (CCL-64), and were nononcogenic in syngeneic mice when the viruses were intrathymically inoculated.

  4. Optimal bidding strategy of battery storage in power markets considering performance based regulation and battery cycle life

    DEFF Research Database (Denmark)

    He, Guannan; Chen, Qixin; Kang, Chongqing

    2016-01-01

    to reduce the complexity of the model. This novel bidding model would help investor-owned battery storages better decide their bidding and operational schedules and investors to estimate the battery storage’s economic viability. The validity of the proposed model is proven by case study results....

  5. An analytical Study on Dynamics of Public Procurement System and Bidding-Strategy in Local Contractor's Management

    Science.gov (United States)

    Ninomiya, Hitoshi; Nanerikawa, Susumu

    Public procurement system such as Overall-Evaluation dynamically has been changed on local public works in Japan. However some characteristics of Bidding-Strategy and procurement system have not enough clarified. This paper attempt to analysis for a syatem dynamics and mechanisum of Overall-Evaluation by developing new simulation model focused on Bidding-Strategy, to propose some improvement scenario.

  6. 48 CFR 32.405 - Applying Pub. L. 85-804 to advance payments under sealed bid contracts.

    Science.gov (United States)

    2010-10-01

    ... advance payments under sealed bid contracts. 32.405 Section 32.405 Federal Acquisition Regulations System... Non-Commercial Items 32.405 Applying Pub. L. 85-804 to advance payments under sealed bid contracts. (a... provisions of law relating to contracts, as explained in 50.101-1(a), also include making advance payments...

  7. 76 FR 6154 - Notice of Realty Action: Modified Competitive Bid Sale of Public Lands in Santa Cruz County, CA

    Science.gov (United States)

    2011-02-03

    ... fair market value of $53,000. The sale will be conducted as a modified competitive bid auction, whereby... than the Federally approved fair market value of $53,000. Each sealed bid must include a certified... values in the land proposed for sale. The proposed sale would include the conveyance of both the surface...

  8. Bid-Ask Spreads, Trading Volume and Return Volatility: Intraday Evidence from Indian Stock Market

    Directory of Open Access Journals (Sweden)

    Rashmi Ranjan Paital

    2016-01-01

    Full Text Available This paper empirically examines the relationship between stock return volatility, trading volume and bid-ask spread within the scope of mixture of distribution hypothesis (MDH and sequential information arrival hypothesis (SIAH in the Indian stock market using high frequency 5-minute data set over the period of 2 July 2012 to 31 December 2012. This is the first kind of study in India using bid-ask spread as an additional information variable along with trading volume to investigate the relationship with stock return volatility. Our empirical findings provide evidence of a positive contemporaneous relationship between return volatility and trading volume, and also between return volatility and bid-ask spread. Moreover, the results of Granger causality test show that the information content of trading volume and bid-ask spread are useful for predicting stock return volatility. Our results indicate that information arrival to investors tends to follow a sequential rather than a simultaneous process. This finding is consistent with the sequential information arrival hypothesis and contradicts the mixture of distribution hypothesis.

  9. 36 CFR 223.84 - Small business bid form provisions on sales with specified road construction.

    Science.gov (United States)

    2010-07-01

    ... provisions on sales with specified road construction. 223.84 Section 223.84 Parks, Forests, and Public... specified road construction. For each sale described in § 223.82(b), the bid form must include provision for a small business concern: (a) To elect road construction by the Forest Service and where such...

  10. 47 CFR 101.1107 - Bidding credits for very small businesses, small businesses and entrepreneurs.

    Science.gov (United States)

    2010-10-01

    ..., small businesses and entrepreneurs. 101.1107 Section 101.1107 Telecommunication FEDERAL COMMUNICATIONS... Procedures for LMDS § 101.1107 Bidding credits for very small businesses, small businesses and entrepreneurs.... (c) A winning bidder that qualifies as an entrepreneur, as defined in § 101.1112, or a consortium of...

  11. Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium

    Czech Academy of Sciences Publication Activity Database

    Driak, D.; Dvorská, M.; Bolehovská, P.; Švandová, Iva; Novotný, J.; Halaška, M.

    2014-01-01

    Roč. 61, č. 4 (2014), s. 411-415 ISSN 0028-2685 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional support: RVO:67985823 Keywords : Bad * Bid * cancerogenesis * human endometrium Subject RIV: CE - Biochemistry Impact factor: 1.865, year: 2014

  12. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA licenses...

  13. Shareholder Wealth Effects of European Domestic and Cross-Border Takeover Bids

    NARCIS (Netherlands)

    Goergen, M.; Renneboog, L.D.R.

    2002-01-01

    In this paper, we analyse the short-term wealth effects of large (intra)European takeover bids.We find large announcement effects of 9% for target firms and a cumulative abnormal return that includes the price run-up over the two-month period prior to the announcement date of 23%.However, the share

  14. Bidding behaviour in multi-unit auctions – an experimental investigation

    Czech Academy of Sciences Publication Activity Database

    Engelmann, Dirk; Grimm, V.

    2009-01-01

    Roč. 119, č. 537 (2009), s. 855-882 ISSN 0013-0133 Institutional research plan: CEZ:AV0Z70850503 Keywords : multi-unit auctions * bidding behavior * laboratory experiments Subject RIV: AH - Economics Impact factor: 1.902, year: 2009

  15. Accounting protesting and warm glow bidding in Contingent Valuation surveys considering the management of environmental goods

    DEFF Research Database (Denmark)

    Grammatikopoulou, Ioanna; Olsen, Søren Bøye

    2013-01-01

    Based on a Contingent Valuation survey aiming to reveal the willingness to pay (WTP) for conservation of a wetland area in Greece, we show how protest and warm glow motives can be taken into account when modeling WTP. In a sample of more than 300 respondents, we find that 54% of the positive bids...

  16. Bid rounds: progress and future prospects; Rodadas de licitacoes: evolucao e perspectivas

    Energy Technology Data Exchange (ETDEWEB)

    Amorelli Junior, D.C.; Silva, Paulo Alexandre S.; Campos, Thiago N. [Agencia Nacional do Petroleo, Gas Natural e Biocombustiveis (ANP), Rio de Janeiro, RJ (Brazil)

    2008-07-01

    The National Agency of Petroleum, Natural Gas and Biofuels - ANP is an institution integrating the indirect Federal Administration, under the special autarchic regime, as an entity regulating the petroleum industry, linked to the Ministry of Mines and Energy - MME. The Minister of MME is the president of the National Council of Energy Policy - CNPE, which has the attribution of proposing national policies and specific measures to the President of the Republic. The ANP aims at promoting the regulation, contraction and inspection of the economic activities related to the petroleum industry, and shall elaborate the bidding protocols and promote the bidding for the concession of exploration, development and production activities, signing the relevant contracts and inspecting its execution. The Brazilian Bidding Rounds of blocks with exploratory risk, promoted by ANP, included areas from 22 of the 38 main Brazilian sedimentary basins divided into three exploratory models: High Potential Areas, New Frontier Areas and Mature Basins Areas. This work presents the framework evolution obtained in Bid Rounds, analyzing the main results of the auctions, and the future perspectives for management of the exploration and production activities according the national energy policy statements. (author)

  17. Optimal bidding strategy for microgrids in joint energy and ancillary service markets considering flexible ramping products

    International Nuclear Information System (INIS)

    Wang, Jianxiao; Zhong, Haiwang; Tang, Wenyuan; Rajagopal, Ram; Xia, Qing; Kang, Chongqing; Wang, Yi

    2017-01-01

    Highlights: •Flexible ramping products are modelled in the framework of a microgrid. •Microgrids’ optimal bidding model is proposed in energy and ancillary service markets. •A hybrid stochastic and robust optimization approach is adopted. •The effectiveness of the proposed bidding model is verified based on real-world data. -- Abstract: Due to the volatile nature of wind and photovoltaic power, wind farms and solar stations are generally thought of as the consumers of ramping services. However, a microgrid (MG) is able to strategically integrate various distributed energy resources (DERs) to provide both energy and ancillary services (ASs) for the bulk power system. To evaluate the ramping capabilities of an MG in the joint energy and AS markets, an optimal bidding strategy is developed in this paper considering flexible ramping products (FRPs). By aggregating and coordinating various DERs, including wind turbines (WTs), photovoltaic systems (PVs), micro-turbines (MTs) and energy storage systems (ESSs), the MG is able to optimally allocate the capacities for energy, spinning reserve and ramping. Taking advantage of the synergy among DERs, the MG can maximize its revenues from different markets. Moreover, the flexibility of the MG for the bulk power system can be fully explored. To address the uncertainties introduced by renewable generation and market prices, a hybrid stochastic/robust optimization (RO) approach is adopted. Case studies based on a real-world MG with various DERs demonstrate the market behavior of the MG using the proposed bidding model.

  18. Normal boundary intersection method for suppliers' strategic bidding in electricity markets: An environmental/economic approach

    International Nuclear Information System (INIS)

    Vahidinasab, V.; Jadid, S.

    2010-01-01

    In this paper the problem of developing optimal bidding strategies for the participants of oligopolistic energy markets is studied. Special attention is given to the impacts of suppliers' emission of pollutants on their bidding strategies. The proposed methodology employs supply function equilibrium (SFE) model to represent the strategic behavior of each supplier and locational marginal pricing mechanism for the market clearing. The optimal bidding strategies are developed mathematically using a bilevel optimization problem where the upper-level subproblem maximizes individual supplier payoff and the lower-level subproblem solves the Independent System Operator's market clearing problem. In order to solve market clearing mechanism the multiobjective optimal power flow is used with supplier emission of pollutants, as an extra objective, subject to the supplier physical constraints. This paper uses normal boundary intersection (NBI) approach for generating Pareto optimal set and then fuzzy decision making to select the best compromise solution. The developed algorithm is applied to an IEEE 30-bus test system. Numerical results demonstrate the potential and effectiveness of the proposed multiobjective approach to develop successful bidding strategies in those energy markets that minimize generation cost and emission of pollutants simultaneously.

  19. Informed trading and the bid-ask spread: evidence from an emerging market

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Podpiera, R.

    2003-01-01

    Roč. 31, č. 2 (2003), s. 275-296 ISSN 0147-5967 R&D Projects: GA MŠk ME 595 Institutional research plan: CEZ:AV0Z7085904 Keywords : market microstructure * bid-ask spread * informed trading Subject RIV: AH - Economics Impact factor: 0.746, year: 2003

  20. Multi-objective optimal strategy for generating and bidding in the power market

    International Nuclear Information System (INIS)

    Peng Chunhua; Sun Huijuan; Guo Jianfeng; Liu Gang

    2012-01-01

    Highlights: ► A new benefit/risk/emission comprehensive generation optimization model is established. ► A hybrid multi-objective differential evolution optimization algorithm is designed. ► Fuzzy set theory and entropy weighting method are employed to extract the general best solution. ► The proposed approach of generating and bidding is efficient for maximizing profit and minimizing both risk and emissions. - Abstract: Based on the coordinated interaction between units output and electricity market prices, the benefit/risk/emission comprehensive generation optimization model with objectives of maximal profit and minimal bidding risk and emissions is established. A hybrid multi-objective differential evolution optimization algorithm, which successfully integrates Pareto non-dominated sorting with differential evolution algorithm and improves individual crowding distance mechanism and mutation strategy to avoid premature and unevenly search, is designed to achieve Pareto optimal set of this model. Moreover, fuzzy set theory and entropy weighting method are employed to extract one of the Pareto optimal solutions as the general best solution. Several optimization runs have been carried out on different cases of generation bidding and scheduling. The results confirm the potential and effectiveness of the proposed approach in solving the multi-objective optimization problem of generation bidding and scheduling. In addition, the comparison with the classical optimization algorithms demonstrates the superiorities of the proposed algorithm such as integrality of Pareto front, well-distributed Pareto-optimal solutions, high search speed.

  1. Controlling market power and price spikes in electricity networks: Demand-side bidding.

    Science.gov (United States)

    Rassenti, Stephen J; Smith, Vernon L; Wilson, Bart J

    2003-03-04

    In this article we report an experiment that examines how demand-side bidding can discipline generators in a market for electric power. First we develop a treatment without demand-side bidding; two large firms are allocated baseload and intermediate cost generators such that either firm might unilaterally withhold the capacity of its intermediate cost generators from the market to benefit from the supracompetitive prices that would result from only selling its baseload units. In a converse treatment, ownership of some of the intermediate cost generators is transferred from each of these firms to two other firms such that no one firm could unilaterally restrict output to spawn supracompetitive prices. Having established a well controlled data set with price spikes paralleling those observed in the naturally occurring economy, we also extend the design to include demand-side bidding. We find that demand-side bidding completely neutralizes the exercise of market power and eliminates price spikes even in the presence of structural market power.

  2. 47 CFR 24.712 - Bidding credits for licenses won for frequency Block C.

    Science.gov (United States)

    2010-10-01

    ... Block C. 24.712 Section 24.712 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON....712 Bidding credits for licenses won for frequency Block C. (a) Except with respect to licenses won in... acquired in either the auction for frequency block C that began on December 18, 1995, or the reauction of...

  3. New approach for strategic bidding of Gencos in energy and spinning reserve markets

    International Nuclear Information System (INIS)

    Soleymani, S.; Ranjbar, A.M.; Shirani, A.R.

    2007-01-01

    In restructured and de-regulated power systems, generating companies (Gencos) are responsible for supplying electricity for both energy and reserve markets, which usually operate simultaneously. In this condition, the question is how much and for what price must each Genco generate for each market to maximize its profit, so this paper intends to answer to this question. In this paper, first, the combined energy and reserve markets are considered, and the Nash equilibrium points are determined. Then, the bidding strategies for each Genco at these points will be presented. The bids for the energy and 10 min spinning reserve (TMSR) markets are separated in the second stage, and again, the bidding strategies for each Genco for the two separated markets will be demonstrated. Comparison of the results shows that the separated bidding strategies, while being simplified with the algebraic optimization model and reducing the time consumed, give the same results as the combined ones. The Western System Coordinating Council (WSCC) nine bus test system is employed to illustrate and verify the results of the proposed method

  4. Stochastic optimal generation bid to electricity markets with emissions risk constraints.

    Science.gov (United States)

    Heredia, F-Javier; Cifuentes-Rubiano, Julián; Corchero, Cristina

    2018-02-01

    There are many factors that influence the day-ahead market bidding strategies of a generation company (GenCo) within the framework of the current energy market. Environmental policy issues are giving rise to emission limitation that are becoming more and more important for fossil-fueled power plants, and these must be considered in their management. This work investigates the influence of the emissions reduction plan and the incorporation of the medium-term derivative commitments in the optimal generation bidding strategy for the day-ahead electricity market. Two different technologies have been considered: the high-emission technology of thermal coal units and the low-emission technology of combined cycle gas turbine units. The Iberian Electricity Market (MIBEL) and the Spanish National Emissions Reduction Plan (NERP) defines the environmental framework for dealing with the day-ahead market bidding strategies. To address emission limitations, we have extended some of the standard risk management methodologies developed for financial markets, such as Value-at-Risk (VaR) and Conditional Value-at-Risk (CVaR), thus leading to the new concept of Conditional Emission at Risk (CEaR). This study offers electricity generation utilities a mathematical model for determining the unit's optimal generation bid to the wholesale electricity market such that it maximizes the long-term profits of the utility while allowing it to abide by the Iberian Electricity Market rules as well as the environmental restrictions set by the Spanish National Emissions Reduction Plan. We analyze the economic implications for a GenCo that includes the environmental restrictions of this National Plan as well as the NERP's effects on the expected profits and the optimal generation bid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Glucocorticoid receptors on leukemic cells as evidenced by dexamethasone-induced cytolysis and /sup 3/H-dexamethasone binding

    Energy Technology Data Exchange (ETDEWEB)

    Thraenhardt, H; Haefer, R; Zintl, F

    1987-01-01

    The presence of glucocorticoid receptors on the leukemic cells of 33 patients affected with acute lymphatic leukemia (ALL) and 6 patients affected with acute myeloic leukemia (AML) was investigated by dexamethasone-induced cytolysis and (/sup 3/H)-dexamethasone binding. The tests undertaken proved that after 20 hours of incubation 9 of 26 non-T-non-B-ALL (c-ALL and unclassified ALL) and 2 of AML were lysed with dexamethasone; blood lymphocytes and bone marrow leukocytes of healthy donors, however, were not affected. Non-T-non-B-ALL and AML were able to bind essentially more (/sup 3/H)-dexamethasone than T-ALL. There existed no correlation between dexamethasone binding and dexamethasone-induced cytolysis.

  6. A 5-year old male with “leukemic form” of disseminated post-transplant lymphoproliferative disorder

    Directory of Open Access Journals (Sweden)

    Saadiya Haque

    2010-03-01

    Full Text Available Post-transplant lymphoproliferative disorder (PTLD represents an abnormal lymphoid proliferation that occurs in recipients of solid organ or bone marrow allograft. It includes a diverse group of diseases ranging from polymorphic B-cell hyperplasia to frank malignant lymphoma. Clinical presentation is variable, ranging from asymptomatic to generalized lymphadenopathy, mononucleosis-like syndrome, nodal or extranodal tumors (usually gastrointestinal tract, systemic lymphomatous involvement, and rare (less than 1% of cases fulminant disseminated disease. PTLD is more common in children than in adults. Younger patients usually present with mononucleosis-like symptoms. We present an unusual case of a 5-year old male who developed a widely disseminated leukemic form of PTLD, involving lymph nodes, tonsils, multiple organs, bone marrow, cerebrospinal fluid, and peripheral blood.

  7. In vitro anti-leukemic activity and chemical transformation of the 5'-chloro-5'-deoxy derivative of cyclo-cytidine

    International Nuclear Information System (INIS)

    Stankovicova, M.; Bachrata, M.; Sveda, P.; Rauko, P.; Blesova, P.

    1995-01-01

    Hydrochloride of 5'-chloro-5'-deoxy-cytocytidine (Cl-cC) is an analogue of hydrochloride (cC), a pro-drug of the compound with of the compound with the strong anti-leukemic activity arabinosylcytosine (araC). This paper is devoted to the study of its cytotoxic activity in vitro and to the effect of acid alkaline conditions and temperature on its stability. Cl-cC inhibits not only the growth of L1210 leukemia cells in vitro and the DNA synthesis (IC 50 = 0.09 μmol/dm 3 ) but, at the same time, it has a weak effect on RNA synthesis (IC 50 > 250 μmol/dm 3 ) and no effect on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5'-chloro-araC and 2',5'-anhydro-araC but is more stable in acid solutions. (author)

  8. Effects of buffers and pH on in vitro binding of 67Ga by L1210 leukemic cells

    International Nuclear Information System (INIS)

    Glickson, J.D.; Webb, J.; Gams, R.A.

    1974-01-01

    The effect of sodium nitrate and a series of buffers on in vitro 67 Ga binding to L1210 leukemic cells at pH 6.8 +- 0.2 and 37 0 at concentrations of 10 -7 to 10 -2 M has been investigated. The relative ability of these agents to inhibit cellular incorporation of 67 Ga is given. Inhibition probably results from formation of gallium(III) complexes which are either impermeable to the tumor membrane or which compete with intracellular receptor complexes. However, direct interaction of buffers with the cell membrane or with gallium(III) receptors, as well as effects of buffers on cellular metabolism, have not been excluded. A monotonic decrease in the cellular incorporation of 67 Ga occurs between pH 6.2 and 7.8 in the presence of the inert buffer, 10 -2 M morpholinopropane sulfonic acid. (U.S.)

  9. Elimination of acute muelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide

    International Nuclear Information System (INIS)

    Sharkis, S.J.; Santos, G.W.; Colvin, M.

    1980-01-01

    Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to purge tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survived before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells

  10. Comparison of edge detection techniques for M7 subtype Leukemic cell in terms of noise filters and threshold value

    Directory of Open Access Journals (Sweden)

    Abdul Salam Afifah Salmi

    2017-01-01

    Full Text Available This paper will focus on the study and identifying various threshold values for two commonly used edge detection techniques, which are Sobel and Canny Edge detection. The idea is to determine which values are apt in giving accurate results in identifying a particular leukemic cell. In addition, evaluating suitability of edge detectors are also essential as feature extraction of the cell depends greatly on image segmentation (edge detection. Firstly, an image of M7 subtype of Acute Myelocytic Leukemia (AML is chosen due to its diagnosing which were found lacking. Next, for an enhancement in image quality, noise filters are applied. Hence, by comparing images with no filter, median and average filter, useful information can be acquired. Each threshold value is fixed with value 0, 0.25 and 0.5. From the investigation found, without any filter, Canny with a threshold value of 0.5 yields the best result.

  11. JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C).

    Science.gov (United States)

    Shami, Paul J; Maciag, Anna E; Eddington, Jordan K; Udupi, Vidya; Kosak, Ken M; Saavedra, Joseph E; Keefer, Larry K

    2009-11-01

    We have designed prodrugs that release nitric oxide (NO) on metabolism by glutathione S-transferases (GST). This design exploits the upregulation of GST in acute myeloid leukemia (AML) cells. O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-leukemic activity. HL-60 myeloid leukemia cells were used for in vitro studies of the combination of JS-K with daunorubicin (DAUNO), cytarabine (ARA-C) or etoposide (ETOP) using the median effect method to determine synergistic, antagonistic, or additive effects. Combinations of JS-K added simultaneously, 2h before or 2h after the other compounds were used. JS-K and DAUNO were antagonistic in all three drug sequences. JS-K and ETOP were also antagonistic but to a lesser degree. JS-K and ARA-C showed strong synergy. The combination index at the 50% fraction affected was 0.37+/-0.23, 0.24+/-0.27, and 0.15+/-0.11 for simultaneous, JS-K first and ARA-C first additions, respectively. JS-K by itself induced DNA strand breaks at relatively high concentrations. However, at submicromolar concentrations, it significantly augmented ARA-C-induced DNA strand breaks. NMR spectroscopy revealed no evidence of chemical interaction between JS-K and the other chemotherapeutic agents. We conclude that ARA-C and JS-K have synergistic anti-leukemic activity and warrant further exploration in combination.

  12. Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus.

    Science.gov (United States)

    Elias, L; Van Epps, D E

    1984-06-01

    The fucose-binding lectin from Lotus tetragonolobus ( FBL -L) has been previously shown to bind specifically to normal cells of the myeloid and monocytic lineages. The purpose of this study was to explore the utility of fluoresceinated FBL -L as a leukemia differentiation marker in conjunction with a panel of other frequently used surface markers (Fc receptor, HLA-DR, OKM1, and antimonocyte antibody). FBL -L reacted with leukemic cells in 8/9 cases of clinically recognized acute myeloid leukemia, including myeloid blast crisis of chronic granulocytic leukemia, 3/3 cases of chronic phase chronic myelogenous leukemia, and in 2/7 cases of clinically undifferentiated acute leukemia. Correlations were noted between reactivity with FBL -L, and DR and Fc receptor expression. Among continuous cell lines, FBL -L bound with high intensity to a majority of HL-60 and U937 cells. The less well differentiated myeloblast cell lines, KG-1, KG1a , and HL-60 blast II, exhibited less FBL -L binding than HL-60 and U937. A moderate proportion of K562 cells exhibited low level binding of FBL -L. Several lymphoblastic cell lines exhibited a pattern of low intensity binding that was distinguishable from the high intensity binding pattern of the myeloblastic lines. FBL -L reactivity of U937 was enhanced by induction of differentiation with leukocyte conditioned medium, but not dimethylsulfoxide. Such treatments induced contrasting patterns of change of HL-60 and U937 when labeled with OKM1, alpha-Mono, and HLA-DR. These studies demonstrate the application of FBL -L to analysis and quantitation of myelomonocytic leukemic differentiation.

  13. BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells.

    Science.gov (United States)

    Poplawski, Tomasz; Blasiak, Janusz

    2010-06-01

    Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.

  14. Isolation of a novel chronic lymphocytic leukemic (CLL) cell line and development of an in vivo mouse model of CLL.

    Science.gov (United States)

    Kellner, Joshua; Wierda, William; Shpall, Elizabeth; Keating, Michael; McNiece, Ian

    2016-01-01

    Leukemic cell lines have become important tools for studies of disease providing a monoclonal cell population that can be extensively expanded in vitro while preserving leukemic cellular characteristics. However, studies of chronic lymphocytic leukemia (CLL) have been impeded in part by the lack of continuous human cell lines. CLL cells have a high spontaneous apoptosis rate in vitro and exhibit minimal proliferation in xenograft models. Therefore, there is a need for development of primary CLL cell lines and we describe the isolation of such a line from the bone marrow of a CLL patient (17p deletion and TP53 mutation) which has been in long term culture for more than 12 months with continuous proliferation. The CLL cell line (termed MDA-BM5) which was generated in vitro with continuous co-culture on autologous stromal cells is CD19+CD5+ and shows an identical pattern of somatic hypermutation as determined in the patient's bone marrow (BM), confirming the origin of the cells from the original CLL clone. MDA-BM5 cells were readily transplantable in NOD/SCID gamma null mice (NSG) with disease developing in the BM, liver and spleen. BM cells from quaternary serial transplantation in NSG mice demonstrated the presence of CD19+CD5+ cells with Ig restricted to lambda which is consistent with the original patient cells. These studies describe a new CLL cell line from a patient with del(17p) that provides a unique model for in vitro and in vivo studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Combining hydro-generation and wind energy. Biddings and operation on electricity spot markets

    International Nuclear Information System (INIS)

    Angarita, Jorge Marquez; Usaola, Julio Garcia

    2007-01-01

    Wind generation is growing rapidly in all the world, especially in Europe. The power produced by this kind of generation is difficult to predict and the predictions are not very accurate. In most systems these imbalances are costly. These penalties reduce the revenue for the wind generation company (WGENCOs). An option to solve this problem would be to work together with another agent. In this paper, a combined strategy for bidding and operating in a power exchange is presented. It considers the combination of a WGENCO and a hydro-generation company (HGENCO). The mathematical formulation for the optimal bids and for the optimal operation is presented, as well as results from realistic cases. (author)

  16. Modeling bidding decision in engineering field with incomplete information: A static game–based approach

    Directory of Open Access Journals (Sweden)

    Zhi-xing Huang

    2016-01-01

    Full Text Available Corporate investment decision about engineering projects is a key issue for project management. This article aims to study the process of bidding decision-making in engineering field under the condition of incomplete information and investigating the influence of bidders’ game behaviors on investment decision. With reasonable assumed scenes, this article uses an approach to describe the decision process for bidding. The approach is based on the static game theory. With the proposed model, the effectiveness of game participants and the objective function are put forward, and the characteristics of price quotation and the best strategies of bidders under the equilibrium condition are discussed. The results can give a better understanding of investment decision in engineering management and are helpful for tenderees to avoid excessive competition among bidders.

  17. Bidding strategy based on artificial intelligence for a competitive electric market

    International Nuclear Information System (INIS)

    Hong, Y.-Y.; Tsai, S.-W.; Weng, M.-T.

    2001-01-01

    A bidding strategy using a fuzzy-c-mean (FCM) algorithm and the artificial neural network (ANN) was developed for competitive electric markets. The nodal price information was assumed to be released into the market. The FCM was used, first, to classify the daily load pattern into peak, medium-peak and off-peak levels and, secondly, to classify the competitive generation companies (gencos) into less-menacing, possible-menacing and menacing gencos. The back-propagation ANN was used for determining the bidding price for a genco. The FCM results aided in lessening the training data and reducing the ANN input nodes. The IEEE 30-busbar system was used for illustrating the applicability of the proposed method. (Author)

  18. Stochastic Optimal Wind Power Bidding Strategy in Short-Term Electricity Market

    DEFF Research Database (Denmark)

    Hu, Weihao; Chen, Zhe; Bak-Jensen, Birgitte

    2012-01-01

    Due to the fluctuating nature and non-perfect forecast of the wind power, the wind power owners are penalized for the imbalance costs of the regulation, when they trade wind power in the short-term liberalized electricity market. Therefore, in this paper a formulation of an imbalance cost...... minimization problem for trading wind power in the short-term electricity market is described, to help the wind power owners optimize their bidding strategy. Stochastic optimization and a Monte Carlo method are adopted to find the optimal bidding strategy for trading wind power in the short-term electricity...... market in order to deal with the uncertainty of the regulation price, the activated regulation of the power system and the forecasted wind power generation. The Danish short-term electricity market and a wind farm in western Denmark are chosen as study cases due to the high wind power penetration here...

  19. New bidding strategy formulation for day-ahead energy and reserve markets based on evolutionary programming

    International Nuclear Information System (INIS)

    Attaviriyanupap, Pathom; Kita, Hiroyuki; Tanaka, Eiichi; Hasegawa, Jun

    2005-01-01

    In this paper, a new bidding strategy for a day-ahead market is formulated. The proposed algorithm is developed from the viewpoint of a generation company wishing to maximize a profit as a participant in the deregulated power and reserve markets. Separate power and reserve markets are considered, both are operated by clearing price auction system. The optimal bidding parameters for both markets are determined by solving an optimization problem that takes unit commitment constraints such as generating limits and unit minimum up/down time constraints into account. This is a non-convex and non-differentiable which is difficult to solve by traditional optimization techniques. In this paper, evolutionary programming is used to solve the problem. The algorithm is applied to both single-sided and double-sided auctions, numerical simulations are carried out to demonstrate the performance of the proposed scheme compared with those obtained from a sequential quadratic programming. (author)

  20. Bidding strategy based on artificial intelligence for a competitive electric market

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Y.-Y.; Tsai, S.-W.; Weng, M.-T. [Chung Yuan Univ., Dept. of Electrical Engineering, Chung Li (China)

    2001-03-01

    A bidding strategy using a fuzzy-c-mean (FCM) algorithm and the artificial neural network (ANN) was developed for competitive electric markets. The nodal price information was assumed to be released into the market. The FCM was used, first, to classify the daily load pattern into peak, medium-peak and off-peak levels and, secondly, to classify the competitive generation companies (gencos) into less-menacing, possible-menacing and menacing gencos. The back-propagation ANN was used for determining the bidding price for a genco. The FCM results aided in lessening the training data and reducing the ANN input nodes. The IEEE 30-busbar system was used for illustrating the applicability of the proposed method. (Author)

  1. Bidding Strategy to Support Decision-Making Based on Comprehensive Information in Construction Projects

    Directory of Open Access Journals (Sweden)

    Ru Liang

    2016-01-01

    Full Text Available This paper develops a unified method to support contractor for bidding selection in construction projects. A cross-functional contractor with 28 candidate units distributed in the three departments (construction units, design units, and suppliers is used as an example. This problem is first formulated as a 0-1 quadratic programming problem through optimizing individual performance and collaborative performance of the candidate units based on individual information and collaborative information. Then, a multiobjective evolutionary algorithm is designed to solve this problem and a bidding selection problem for a major bridge project is used to demonstrate our proposed method. The results show that the decision-maker (DM obtains a better contractor if he pays more attention to collaborative performance.

  2. Paying Medicare Advantage plans by competitive bidding: how much competition is there?

    Science.gov (United States)

    Biles, Brian; Pozen, Jonah; Guterman, Stuart

    2009-08-01

    Private health plans that enroll Medicare beneficiaries--known as Medicare Advantage (MA) plans--are being paid $11 billion more in 2009 than it would cost to cover these beneficiaries in regular fee-for-service Medicare. To generate Medicare savings for offsetting the costs of health reform, the Obama Administration has proposed eliminating these extra payments to private insurers and instituting a competitive bidding system that pays MA plans based on the bids they submit. This study examines the concentration of enrollment among MA plans and the degree to which firms offering MA plans actually face competition. The results show that in the large majority of U.S. counties, MA plan enrollment is highly concentrated in a small number of firms. Given the relative lack of competition in many markets as well as the potential impact on traditional Medicare, the authors call for careful consideration of a new system for setting MA plan payments.

  3. Bidding strategy for pumped-storage plant in pool-based electricity market

    International Nuclear Information System (INIS)

    Kanakasabapathy, P.; Shanti Swarup, K.

    2010-01-01

    This paper develops optimal bidding strategies for a pumped-storage plant in a pool-based electricity market. In the competitive regime, when compared to simple hydroelectric generator, profit of the pumped-storage plant is maximized by operating it as a generator when market clearing price is high and as a pump when the price is low. Based on forecasted hourly market clearing price, a multistage looping algorithm to maximize the profit of a pumped-storage plant is developed, considering both the spinning and non-spinning reserve bids and meeting the technical operating constraints of the plant. The proposed model is adaptive for the nonlinear three-dimensional relationship between the power produced, the energy stored, and the head of the associated reservoir. Different operating cycles for a realistic pumped-storage plant are considered and simulation results are reported and compared. (author)

  4. Price-Taker Offering Strategy in Electricity Pay-as-Bid Markets

    DEFF Research Database (Denmark)

    Mazzi, Nicolò; Kazempour, Jalal; Pinson, Pierre

    2017-01-01

    The recent increase in the deployment of renewable energy sources may affect the offering strategy of conventional producers, mainly in the balancing market. The topics of optimal offering strategy and self-scheduling of thermal units have been extensively addressed in the literature. The feasible...... operating region of such units can be modeled using a mixed-integer linear programming approach, and the trading problem as a linear programming problem. However, the existing models mostly assume a uniform pricing scheme in all market stages, while several European balancing markets (e.g., in Germany...... and Italy) are settled under a pay-as-bid pricing scheme. The existing tools for solving the trading problem in pay-as-bid electricity markets rely on non-linear optimization models, which, combined with the unit commitment constraints, result in a mixed-integer non-linear programming problem. In contrast...

  5. Human TM9SF4 Is a New Gene Down-Regulated by Hypoxia and Involved in Cell Adhesion of Leukemic Cells.

    Directory of Open Access Journals (Sweden)

    Rosa Paolillo

    Full Text Available The transmembrane 9 superfamily protein member 4, TM9SF4, belongs to the TM9SF family of proteins highly conserved through evolution. TM9SF4 homologs, previously identified in many different species, were mainly involved in cellular adhesion, innate immunity and phagocytosis. In human, the function and biological significance of TM9SF4 are currently under investigation. However, TM9SF4 was found overexpressed in human metastatic melanoma and in a small subset of acute myeloid leukemia (AMLs and myelodysplastic syndromes, consistent with an oncogenic function of this gene.In this study, we first analyzed the expression and regulation of TM9SF4 in normal and leukemic cells and identified TM9SF4 as a gene highly expressed in human quiescent CD34+ hematopoietic progenitor cells (HPCs, regulated during monocytic and granulocytic differentiation of HPCs, both lineages giving rise to mature myeloid cells involved in adhesion, phagocytosis and immunity. Then, we found that TM9SF4 is markedly overexpressed in leukemic cells and in AMLs, particularly in M2, M3 and M4 AMLs (i.e., in AMLs characterized by the presence of a more or less differentiated granulocytic progeny, as compared to normal CD34+ HPCs. Proliferation and differentiation of HPCs occurs in hypoxia, a physiological condition in bone marrow, but also a crucial component of cancer microenvironment. Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.Altogether, our study reports for the first time the expression of TM9SF4 at the level of normal and leukemic hematopoietic cells and its marked expression at the level of AMLs

  6. Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells.

    Science.gov (United States)

    Curti, Antonio; Trabanelli, Sara; Onofri, Chiara; Aluigi, Michela; Salvestrini, Valentina; Ocadlikova, Darina; Evangelisti, Cecilia; Rutella, Sergio; De Cristofaro, Raimondo; Ottaviani, Emanuela; Baccarani, Michele; Lemoli, Roberto M

    2010-12-01

    The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein. These data identify

  7. National Emission Standards for Hazardous Air Pollutants (NESHAP) for Lime Manufacturing Background Information Document (BID): Public Comments and Responses

    Science.gov (United States)

    On December 20, 2002, the EPA proposed national emission standards for HAP emissions from lime manufacturing plants located at major source facilities (67 FR 78046). Summaries of the comments, and the EPA's responses, are presented in this BID.

  8. Uranium Mill Tailings Remedial Action Project (UMTRAP), Slick Rock, Colorado, Revision 1. Bid schedule, special conditions, specifications, and subcontract drawings

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    This volume contains: bidding requirements; terms and conditions; specifications for Division 1 -- general requirements; specifications for Division 2 -- sitework; specifications for Divisions 5 -- metals; subcontract drawings, (general, Union Carbide processing site, North Continent processing site, and Burro Canyon disposal site).

  9. 48 CFR 9904.420 - Accounting for independent research and development costs and bid and proposal costs.

    Science.gov (United States)

    2010-10-01

    ... Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.420 Accounting for independent research and development costs and bid and proposal costs. ...

  10. Uranium Mill Tailings Remedial Action Project (UMTRAP), Slick Rock, Colorado, Revision 1. Bid schedule, special conditions, specifications, and subcontract drawings

    International Nuclear Information System (INIS)

    1995-01-01

    This volume contains: bidding requirements; terms and conditions; specifications for Division 1 -- general requirements; specifications for Division 2 -- sitework; specifications for Divisions 5 -- metals; subcontract drawings, (general, Union Carbide processing site, North Continent processing site, and Burro Canyon disposal site)

  11. The Price Is Right, but Are the Bids? An Investigation of Rational Decision Theory.

    OpenAIRE

    Berk, Jonathan B; Hughson, Eric; Vandezande, Kirk

    1996-01-01

    The television game show The Price Is Right is used as a laboratory to conduct a preference-free test of rational decision theory in an environment with substantial economic incentives. It is found that contestants' strategies are transparently suboptimal. In response to this evidence, simple rules of thumb are developed that are shown to explain observed bidding patterns better than rational decision theory. Further, learning during the show reduces the frequency of strategic errors. This is...

  12. Eesti tüübid : meie siin maal / Maris Rosenthal

    Index Scriptorium Estoniae

    Rosenthal, Maris

    2009-01-01

    Eesti Rahva Muuseumi ja fotograaf Alar Madissoni projekti "Eesti tüübid" raames valminud fotonäitus "Meie siin maal" Tartus Raadi mõisapargis. Kaasaega dokumenteeriva projekti eesmärgiks oli jäädvustada kõigis Eesti maakondades elavaid eri generatsioonide ja sotsiaalsete rühmade esindajaid ERMi fotokogu täiendamiseks. Meenutusi pildistamistelt 2008. aasta suvel

  13. Manufacturers’ Bids for WIC Infant Formula Rebate Contracts, 2003-2013

    OpenAIRE

    Oliveira, Victor; Davis, David

    2015-01-01

    The U.S. Department of Agriculture’s Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is the major purchaser of infant formula in the United States, and its mandatory rebate program saved WIC $1.9 billion in FY 2013. WIC State agencies are required by law to have competitively bid infant formula rebate contracts with infant formula manufacturers. Contracts are awarded to the manufacturer offering the WIC State agency the lowest net price (as determined by the manu...

  14. Bidding Strategy of Virtual Power Plant with Energy Storage Power Station and Photovoltaic and Wind Power

    Directory of Open Access Journals (Sweden)

    Zhongfu Tan

    2018-01-01

    Full Text Available For the virtual power plants containing energy storage power stations and photovoltaic and wind power, the output of PV and wind power is uncertain and virtual power plants must consider this uncertainty when they participate in the auction in the electricity market. In this context, this paper studies the bidding strategy of the virtual power plant with photovoltaic and wind power. Assuming that the upper and lower limits of the combined output of photovoltaic and wind power are stochastically variable, the fluctuation range of the day-ahead energy market and capacity price is stochastically variable. If the capacity of the storage station is large enough to stabilize the fluctuation of the output of the wind and photovoltaic power, virtual power plants can participate in the electricity market bidding. This paper constructs a robust optimization model of virtual power plant bidding strategy in the electricity market, which considers the cost of charge and discharge of energy storage power station and transmission congestion. The model proposed in this paper is solved by CPLEX; the example results show that the model is reasonable and the method is valid.

  15. Understanding Irrigator Bidding Behavior in Australian Water Markets in Response to Uncertainty

    Directory of Open Access Journals (Sweden)

    Alec Zuo

    2014-11-01

    Full Text Available Water markets have been used by Australian irrigators as a way to reduce risk and uncertainty in times of low water allocations and rainfall. However, little is known about how irrigators’ bidding trading behavior in water markets compares to other markets, nor is it known what role uncertainty and a lack of water in a variable and changing climate plays in influencing behavior. This paper studies irrigator behavior in Victorian water markets over a decade (a time period that included a severe drought. In particular, it studies the evidence for price clustering (when water bids/offers end mostly around particular numbers, a common phenomenon present in other established markets. We found that clustering in bid/offer prices in Victorian water allocation markets was influenced by uncertainty and strategic behavior. Water traders evaluate the costs and benefits of clustering and act according to their risk aversion levels. Water market buyer clustering behavior was mostly explained by increased market uncertainty (in particular, hotter and drier conditions, while seller-clustering behavior is mostly explained by strategic behavioral factors which evaluate the costs and benefits of clustering.

  16. Aspects if stochastic models for short-term hydropower scheduling and bidding

    Energy Technology Data Exchange (ETDEWEB)

    Belsnes, Michael Martin [Sintef Energy, Trondheim (Norway); Follestad, Turid [Sintef Energy, Trondheim (Norway); Wolfgang, Ove [Sintef Energy, Trondheim (Norway); Fosso, Olav B. [Dep. of electric power engineering NTNU, Trondheim (Norway)

    2012-07-01

    This report discusses challenges met when turning from deterministic to stochastic decision support models for short-term hydropower scheduling and bidding. The report describes characteristics of the short-term scheduling and bidding problem, different market and bidding strategies, and how a stochastic optimization model can be formulated. A review of approaches for stochastic short-term modelling and stochastic modelling for the input variables inflow and market prices is given. The report discusses methods for approximating the predictive distribution of uncertain variables by scenario trees. Benefits of using a stochastic over a deterministic model are illustrated by a case study, where increased profit is obtained to a varying degree depending on the reservoir filling and price structure. Finally, an approach for assessing the effect of using a size restricted scenario tree to approximate the predictive distribution for stochastic input variables is described. The report is a summary of the findings of Work package 1 of the research project #Left Double Quotation Mark#Optimal short-term scheduling of wind and hydro resources#Right Double Quotation Mark#. The project aims at developing a prototype for an operational stochastic short-term scheduling model. Based on the investigations summarized in the report, it is concluded that using a deterministic equivalent formulation of the stochastic optimization problem is convenient and sufficient for obtaining a working prototype. (author)

  17. Business valuation: an analysis of projected cash flows versus takeover bids

    Directory of Open Access Journals (Sweden)

    Camila Menezes

    2017-12-01

    Full Text Available One of the main financial statements is the Cash Flow. It became mandatory from the law # 11,638/2007 on, which changed the law # 6,404/1976 – the Corporations’ law, and the Cash Flow statement allows analysis about the companies’ operations activities effects, investing and financing, highlighting their main sources of financial allocation. In 2005 and 2006, 37 companies registered takeover bids in the Brazilian Securities Exchange Commission (CVM – Comissão de Valores Mobiliários. Based on these companies’ analysis of Projected Cash Flows (FCP – Fluxos de Caixa Projetados when the takeover bids were put in place and their Actual Cash Flows (FCR – Fluxo de Caixa Realizados the objective of this work was to compare those cash flows, to analyze the differences between the Statements of Cash Flows attached to the Appraisal Reports and the actual ones, as well as to check if these companies’ cash were in line with the balances projected in the takeover bids. The obtained results via statistical analysis of differences between the Projected Cash Flows attached to the Appraisal Reports and the effective Actual Cash Flows, all of them compared in the period between 2007 and 2013, did not show significant differences among them. IE: it was observed that, nevertheless the companies did not accomplish the promised Cash Flows delivery when the OPAs were put in place, the differences between the balances projected and the actual ones were not statistically significant.

  18. A combination of SILAC and nucleotide acyl phosphate labelling reveals unexpected targets of the Rsk inhibitor BI-D1870.

    Science.gov (United States)

    Edgar, Alexander J; Trost, Matthias; Watts, Colin; Zaru, Rossana

    2014-02-01

    Protein kinase inhibitors frequently have interesting effects that cannot be fully ascribed to the intended target kinase(s) but identifying additional targets that might explain the effects is not straightforward. By comparing two different inhibitors of the Rsk (p90 ribosomal S6 kinase) kinases, we found that the increasingly used compound BI-D1870 had biological effects in murine DCs (dendritic cells) that could not be solely ascribed to Rsk or other documented targets. We assessed the ability of BI-D1870 and a second Rsk inhibitor, BIX 02565 to protect enzyme active sites from reaction with biotinylated nucleotide acyl phosphates. Using SILAC (stable isotope labelling by amino acids in cell culture)-labelled DC lysates as a source of enzyme targets, we identify several kinases that interact with BI-D1870 but not with BIX 02565. We confirmed that these kinases, including Slk, Lok and Mst1, are inhibited by BI-D1870 but to a much lesser extent by BIX 02565 and that phosphorylation of some of their substrates is blocked by BI-D1870 in living cells. Our results suggest that the BI-D1870 inhibitor should be used with caution. The SILAC-based methodology we used should be useful for further comparative unbiased profiling of the target spectrum of kinase inhibitors with interesting biological effects under conditions that closely mimic those found in cells. © 2014 The author(s).

  19. The effect of virtual bidding on forward premiums in the New York wholesale energy market

    Science.gov (United States)

    Knudsen, Andrew D.

    In many parts of the United States, the power industry has been deregulated and replaced with regional wholesale energy markets, where utilities purchase electricity from generators at competitive market rates for subsequent distribution to customers. Numerous studies have shown that in each of these markets, the price of energy purchased in the Day Ahead (futures) market exceeds the price in the Real Time (spot) market on average. The existence of this "forward premium" is evidence of market inefficiency and may indicate participants' aversion to risk in the Real Time market or the exercise of market power by generators. To address this inefficiency, the New York Independent System Operator introduced a virtual bidding system within its wholesale market, which permitted participants to engage in purely financial transactions and hedge their exposure to risk. The new policy was expected to promote price convergence by allowing bidders to arbitrage expected differences between Day Ahead and Real Time prices. This study examines whether the presence of virtual bidding was associated with a change in the mean value and magnitude of forward premiums in the NYISO energy market. The study applies a GARCH model to hourly pricing data from 2001 to 2009, controlling for temperature and economic activity. The results indicate that prior to 2005, virtual bidding was associated with significantly lower and less volatile forward premiums in New York's five most congested zones but with increased premiums in the remaining less congested zones. However, when the entire period from 2001 to 2009 is examined, the results suggest that prices have become significantly more divergent in the presence of virtual bidding. Closer examination of the data reveals a dramatic increase in forward premium volatility across all zones beginning in 2005 that is not accounted for by temperature or economic activity and may have biased the results. This study attempts to account for this unexplained

  20. Involvement of CD147 on multidrug resistance through the regulation of P-glycoprotein expression in K562/ADR leukemic cell line

    Directory of Open Access Journals (Sweden)

    Aoranit Somno

    2016-01-01

    Full Text Available The relationship between P-gp and CD147 in the regulation of MDR in leukemic cells has not been reported. This study aimed to investigate the correlation between CD147 and P-gp in the regulation of drug resistance in the K562/ADR leukemic cell line. The results showed that drug-resistant K562/ADR cells expressed significantly higher P-gp and CD147 levels than drug-free K562/ADR cells. To determine the regulatory effect of CD147 on P-gp expression, anti-CD147 antibody MEM-M6/6 significantly decreased P-gp and CD147 mRNA and protein levels. This is the first report to show that CD147 mediates MDR in leukemia through the regulation of P-gp expression.

  1. Resource use and costs of exenatide bid or insulin in clinical practice: the European CHOICE study

    Directory of Open Access Journals (Sweden)

    Kiiskinen U

    2013-07-01

    Full Text Available Urpo Kiiskinen,1 Stephan Matthaei,2 Matthew Reaney,3 Chantal Mathieu,4 Claes-Göran Östenson,5 Thure Krarup,6 Michael Theodorakis,7,* Jacek Kiljanski,8 Carole Salaun-Martin,9 Hélène Sapin,9 Bruno Guerci10 1Eli Lilly, Helsinki, Finland; 2Quakenbrück Diabetes Center, Quakenbrück, Germany; 3Eli Lilly, Windlesham, Surrey, UK; 4Department of Endocrinology, UZ Gasthuisberg, Leuven, Belgium; 5Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 6Department of Endocrinology, Bispebjerg Hospital, Copenhagen, Denmark; 7Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; 8Eli Lilly, Warsaw, Poland; 9Eli Lilly, Neuilly Cedex, France; 10Department of Diabetes, Metabolic Diseases, and Nutrition, Hôpital Brabois, Vandoeuvre-Lès-Nancy, France *Michael Theodorakis was affiliated with the institution shown above at the time of the study, but has since left this institution Purpose: CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy assessed patterns of exenatide bid and initial insulin therapy usage in clinical practice in six European countries and evaluated outcomes during the study. Methods: CHOICE was a 24-month, prospective, noninterventional observational study. Clinical and resource use data were collected at initiation of first injectable therapy (exenatide bid or insulin and at regular intervals for 24 months. Costs were evaluated from the national health care system perspective at 2009 prices. Results: A total of 2515 patients were recruited. At the 24-month analysis, significant treatment change had occurred during the study in 42.2% of 1114 eligible patients in the exenatide bid cohort and 36.0% of 1274 eligible patients in the insulin cohort. Improvements in glycemic control were observed over the course of the study in both cohorts (P < 0.001 for both, but mean weight was reduced in the exenatide bid cohort (P < 0

  2. Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

    OpenAIRE

    Curti, A; Trabanelli, S; Onofri, C; Aluigi, M; Salvestrini, V; Ocadlikova, D; Evangelisti, C; Rutella, S; De Cristofaro, R; Ottaviani, E; Baccarani, M; Lemoli, RM

    2010-01-01

    Background: The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia.\\ud Design and Methods: Leukemic d...

  3. Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation.

    Science.gov (United States)

    van den Ancker, Willemijn; van Luijn, Marvin M; Ruben, Jurjen M; Westers, Theresia M; Bontkes, Hetty J; Ossenkoppele, Gert J; de Gruijl, Tanja D; van de Loosdrecht, Arjan A

    2011-01-01

    Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE(2)) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20-30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation.

  4. Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

    Directory of Open Access Journals (Sweden)

    Salvador Valle-Reyes

    2018-05-01

    Full Text Available Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+- or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3. Voltage dependence of activation and inactivation of Kv1.3 current were shifted up to by 15 mV to more negative potentials upon a prolonged incubation in the whole cell mode and displayed little difference at a stable state in all cell lines but CEM, where the activation curve was biphasic, with a high and low potential components. In Jurkat, KCa currents were dominated by apamine-sensitive KCa2.2 channels, whereas only KCa3.1 current was detected in healthy T and leukemic CEM and MOLT-3 cells. Despite a high proliferation potential of Jurkat cells, Kv and KCa currents were unexpectedly small, more than 10-fold lesser as compared to activated healthy human T cells, CEM and MOLT-3, which displayed characteristic Kv1.3high:KCa3.1high phenotype. Our results suggest that Jurkat cells represent perhaps a singular case and call for more extensive studies on primary leukemic T cell lines as well as a verification of the therapeutic potential of specific KCa3.1 blockers to combat acute lymphoblastic T leukemias.

  5. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods.

    Science.gov (United States)

    Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga

    2010-01-01

    Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

  6. Novel quinazolinone MJ-29 triggers endoplasmic reticulum stress and intrinsic apoptosis in murine leukemia WEHI-3 cells and inhibits leukemic mice.

    Directory of Open Access Journals (Sweden)

    Chi-Cheng Lu

    Full Text Available The present study was to explore the biological responses of the newly compound, MJ-29 in murine myelomonocytic leukemia WEHI-3 cells in vitro and in vivo fates. We focused on the in vitro effects of MJ-29 on ER stress and mitochondria-dependent apoptotic death in WEHI-3 cells, and to hypothesize that MJ-29 might fully impair the orthotopic leukemic mice. Our results indicated that a concentration-dependent decrease of cell viability was shown in MJ-29-treated cells. DNA content was examined utilizing flow cytometry, whereas apoptotic populations were determined using annexin V/PI, DAPI staining and TUNEL assay. Increasing vital factors of mitochondrial dysfunction by MJ-29 were further investigated. Thus, MJ-29-provaked apoptosis of WEHI-3 cells is mediated through the intrinsic pathway. Importantly, intracellular Ca(2+ release and ER stress-associated signaling also contributed to MJ-29-triggered cell apoptosis. We found that MJ-29 stimulated the protein levels of calpain 1, CHOP and p-eIF2α pathways in WEHI-3 cells. In in vivo experiments, intraperitoneal administration of MJ-29 significantly improved the total survival rate, enhanced body weight and attenuated enlarged spleen and liver tissues in leukemic mice. The infiltration of immature myeloblastic cells into splenic red pulp was reduced in MJ-29-treated leukemic mice. Moreover, MJ-29 increased the differentiations of T and B cells but decreased that of macrophages and monocytes. Additionally, MJ-29-stimulated immune responses might be involved in anti-leukemic activity in vivo. Based on these observations, MJ-29 suppresses WEHI-3 cells in vitro and in vivo, and it is proposed that this potent and selective agent could be a new chemotherapeutic candidate for anti-leukemia in the future.

  7. Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways.

    Science.gov (United States)

    Wang, Hongfei; Wang, Yongqiang; Gao, Hongmei; Wang, Bing; Dou, Lin; Li, Yin

    2018-02-01

    Piperlongumine is an alkaloid compound extracted from Piper longum L. It is a chemical substance with various pharmacological effects and medicinal value, including anti-tumor, lipid metabolism regulatory, antiplatelet aggregation and analgesic properties. The present study aimed to understand whether piperlongumine induces the apoptosis and autophagy of leukemic cells, and to identify the mechanism involved. Cell viability and autophagy were detected using MTT, phenazine methyl sulfate and trypan blue exclusion assays. The apoptosis rate was calculated using flow cytometry. The protein expression levels of microtubule-associated protein 1A/1B-light chain 3, Akt and mechanistic target of rapamycin (mTOR) were measured using western blotting. The cell growth of leukemic cells was completely inhibited following treatment with piperlongumine, and marked apoptosis was also induced. Dead cells as a result of autophagy were stained using immunofluorescence and observed under a light microscope. Phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was suppressed by treatment with piperlongumine, while p38 signaling and caspase-3 activity were induced by treatment with piperlongumine. It was concluded that piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways.

  8. In vitro proliferation of normal and leukemic human leukocytes controlled by an inhibitory endopeptide. [/sup 3/H-TdR incorporation

    Energy Technology Data Exchange (ETDEWEB)

    Balazs, A; Mann, J; Takacsi-Nagy, L; Zimonyi, I; Molnar, A; Klupp, T [Inst. of Experimental Medicine, Budapest (Hungary); Istvan Municipal Hospital, Budapest (Hungary); Heim Pal Children' s Hospital Budapest, (Hungary))

    1983-01-01

    GI-3, an endogenous inhibitory fraction isolated from leukocytes, selectively inhibits the proliferation of granuloid precursor cells in a non-toxic manner. Its active principle is an acidic chlor-tolidine positive decapeptide. The in vitro effect on normal and acute leukemic human bone marrow and blood cells was examined. A dose dependent inhibition by GI-3 of /sup 3/H-TdR incorporation into myeloid cells of normal bone marrow was found, the sensitivity of human cells being higher than that of rat cells. The proliferation of the target leukemic bone marrow and blood cells was also decreased by the endogenous inhibitor in a dose-dependent manner in untreated subjects as well as in patients in remission or relapse. The rate of inhibition of leukemic cell proliferation in the short-term suspension system examined almost coincided with the action of well-known cytostatics applied for comparison. Beyond its direct cytostatic effect, GI-3 could be used in the differential diagnosis of blastic leukemias, complementing the routine cytochemical methods.

  9. Transfer RNA species in human lymphocytes stimulated by mitogens and in leukemic cells. [/sup 3/H, /sup 14/C, /sup 32/P tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Yang, W.K.; Novelli, G.D.

    1976-01-01

    Transfer ribonucleic acid (tRNA) profiles in human lymphocytes stimulated by various mitogens have been compared with profiles from nonstimulated cells and from leukemic cells using reversed-phase chromatography. Comparisons of (/sup 3/H)- or (/sup 11/C)uridine- or (/sup 32/P)phosphate-labeled tRNAs showed that the greatest changes in tRNA composition upon phytohemagglutinin (PHA) stimulation occurred in the first 8 h after mitogen addition. Stimulation of lymphocytes by pokeweed mitogen, anti-human immunoglobulin, or bacterial lipopolysaccharide resulted in tRNA species which showed distinct differences from each other and also from the tRNAs produced by phytohemagglutinin stimulation. Leukemic lymphocyte tRNAs showed the most extensive differences in profile when compared with chromatograms from non-neoplastic cells stimulated by a variety of mitogens. Specific isoaccepting species of tyrosyl-, aspartyl-, and phenylalanyl-tRNAs were also compared in PHA-stimulated and resting lymphocytes and no differences were found. When these same species were studied in leukemic cells, tyrosyl-tRNA profiles were shifted to elute at a lower salt concentration, while the aspartyl-tRNA profile showed a new peak not present in noncancerous cells.

  10. Inhibitory effect of turmeric curcuminoids on FLT3 expression and cell cycle arrest in the FLT3-overexpressing EoL-1 leukemic cell line.

    Science.gov (United States)

    Tima, Singkome; Ichikawa, Hideki; Ampasavate, Chadarat; Okonogi, Siriporn; Anuchapreeda, Songyot

    2014-04-25

    Leukemia is a hematologic malignancy with a frequent incidence and high mortality rate. Previous studies have shown that the FLT3 gene is overexpressed in leukemic blast cells, especially in acute myeloid leukemia. In this study, a commercially available curcuminoid mixture (1), pure curcumin (2), pure demethoxycurcumin (3), and pure bisdemethoxycurcumin (4) were investigated for their inhibitory effects on cell growth, FLT3 expression, and cell cycle progression in an FLT3-overexpressing EoL-1 leukemic cell line using an MTT assay, Western blotting, and flow cytometry, respectively. The mixture (1) and compounds 2-4 demonstrated cytotoxic effects with IC50 values ranging from 6.5 to 22.5 μM. A significant decrease in FLT3 protein levels was found after curcuminoid treatment with IC20 doses, especially with mixture 1 and compound 2. In addition, mixture 1 and curcumin (2) showed activity on cell cycle arrest at the G0/G1 phase and decreased the FLT3 and STAT5A protein levels in a dose-dependent manner. Compound 2 demonstrated the greatest potential for inhibiting cell growth, cell cycle progression, and FLT3 expression in EoL-1 cells. This investigation has provided new findings regarding the effect of turmeric curcuminoids on FLT3 expression in leukemic cells.

  11. Leukemic transformation of donor spleen cells following their transplantation into supralethally irradiated mice with pre-existing viral leukemia. [X Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnert, P M; OKunewick, J P; Erhard, P

    1974-01-01

    Fialkow et al. previously reported leukemia induction in donor-type cells after treating patients for acute lymphoblastic leukemia with total-body irradiation and hematopoietic cell transplantation. Utilizing a murine model and paralleling their treatment protocol, we have documented that induction of leukemia can occur in normal donor cells transplanted into Rauscher viral leukemic mice at 0, 1 and 2 days after irradiation. The induction of leukemia in the grafted cells was verified by: the occurrence of splenomegaly; and secondary spleen cell transplants, whereby the secondary donors were transplanted mice still alive at 30 days and the secondary recipients were normal unirradiated mice. The spleen weights of the grafted leukemic mice were found to be significantly greater than those of the controls and all secondary recipients that received spleen cells from the primary grafted leukemic mice also died of leukemia. Verification that the regenerating hematopoietic tissue was from donor (males) and not host source (females) was accomplished by spleen chromosome preparations taken from randomly selected mice at 14 and at 30 days after cell transplantation. In these preparations, the Y chromosome was clearly distinguishable on the basis of size, shape, and differential staining. The data indicate that induction of leukemia after whole-body irradiation and hematopoietic cell transplantation can occur in immunologically matched donor cells when a viral agent is present and that the incidence of this induction is not affected by a time delay between irradiation and transplant.

  12. Fludarabine-mediated circumvention of cytarabine resistance is associated with fludarabine triphosphate accumulation in cytarabine-resistant leukemic cells.

    Science.gov (United States)

    Yamamoto, Shuji; Yamauchi, Takahiro; Kawai, Yasukazu; Takemura, Haruyuki; Kishi, Shinji; Yoshida, Akira; Urasaki, Yoshimasa; Iwasaki, Hiromichi; Ueda, Takanori

    2007-02-01

    The combination of cytarabine (ara-C) with fludarabine is a common approach to treating resistant acute myeloid leukemia. Success depends on a fludarabine triphosphate (F-ara-ATP)-mediated increase in the active intracellular metabolite of ara-C, ara-C 5'-triphosphate (ara-CTP). Therapy-resistant leukemia may exhibit ara-C resistance, the mechanisms of which might induce cross-resistance to fludarabine with reduced F-ara-ATP formation. The present study evaluated the effect of combining ara-C and fludarabine on ara-C-resistant leukemic cells in vitro. Two variant cell lines (R1 and R2) were 8-fold and 10-fold more ara-C resistant, respectively, than the parental HL-60 cells. Reduced deoxycytidine kinase activity was demonstrated in R1 and R2 cells, and R2 cells also showed an increase in cytosolic 5'-nucleotidase II activity. Compared with HL-60 cells, R1 and R2 cells produced smaller amounts of ara-CTP. Both variants accumulated less F-ara-ATP than HL-60 cells and showed cross-resistance to fludarabine nucleoside (F-ara-A). R2 cells, however, accumulated much smaller amounts of F-ara-ATP and were more F-ara-A resistant than R1 cells. In HL-60 and R1 cells, F-ara-A pretreatment followed by ara-C incubation produced F-ara-ATP concentrations sufficient for augmenting ara-CTP production, thereby enhancing ara-C cytotoxicity. No potentiation was observed in R2 cells. Nucleotidase might preferentially degrade F-ara-A monophosphate over ara-C monophosphate, leading to reduced F-ara-ATP production and thereby compromising the F-ara-A-mediated potentiation of ara-C cytotoxicity in R2 cells. Thus, F-ara-A-mediated enhancement of ara-C cytotoxicity depended on F-ara-ATP accumulation in ara-C-resistant leukemic cells but ultimately was associated with the mechanism of ara-C resistance.

  13. Assay of hybrid ribonuclease using a membrane filter-immobilized synthetic hybrid: application to the human leukemic cell

    International Nuclear Information System (INIS)

    Papaphilis, A.D.; Kamper, E.F.

    1985-01-01

    A method for assaying hybrid ribonuclease has been devised which utilizes as substrate the synthetic hybrid [ 3 H]polyriboadenylic acid [poly(rA)]:polydeoxythymidylic acid [poly(dT)] immobilized on the solid matrix of nitrocellulose filters. The hybridization on filter of [ 3 H]poly(rA) to poly(dT) has been explored in terms of efficacy of the process and the response of the product to RNase H. A pulse of uv irradiation of poly(dT) while in dry state on the filter increased its firm binding to the filter in a concentration-dependent manner, resulting in a concomitant increase of the yield of hybrid formation. The filter-immobilized hybrid was 95% resistant to RNase A but sensitive to RNase H. When stored in toluene in the cold the hybrid maintained its stability for over 6 months, as judged by its resistance to RNase A. The method offers a number of advantages over assays that use solution hybrids as substrates and was readily applicable in the screening of leukemic patients, in the leukocytes of which it has demonstrated increased RNase H levels

  14. Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540

    International Nuclear Information System (INIS)

    Porcellini, A.; Talevi, N.; Marchetti-Rossi, M.T.; Palazzi, M.; Manna, A.; Sparaventi, G.; Delfini, C.; Valentini, M.

    1987-01-01

    To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation

  15. Correlation of chromosome patterns in leukemic cells of patients with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    Rowley, J.D.

    1989-10-01

    We have identified two new recurring translocations involving chromosome 5; one is a 3;5 translocation and the other involves a rearrangement between chromosomes 5 and 7. The first is t(3;5)(q25.1;q35). We studied five patients with AML and a t(3;5) in their leukemic cells. At diagnosis, four of the patients had a t(3;5) as their sole karyotypic anomaly; the remaining patient had additional structural and numerical abnormalities. Careful cytogenetic analysis indicated that the breakpoints of this rearrangement were 3q25.1 and 5q34, in contrast to the various breakpoints reported in earlier studies (3q21 to 3q25 and 5q31 to 5q35). The karyotypic, morphologic, and clinical characteristics of this group, as well as those of 15 previously reported patients with the t(3;5), were compared to identify any features that might warrant consideration of this anomaly as a specific syndrome. The median age of the group, 37 years, as younger than that of all patients with AML, 49 years. A preceding myelodysplastic syndrome was observed in three patients. We have no information regarding the occupation of most of these patients. Except for acute promyelocytic leukemia, each morphologic subtype occurred in these patients; however, the frequency of erythroleukemia (M6) was much greater than expected. 11 refs., 2 figs., 5 tabs

  16. GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis.

    Science.gov (United States)

    Dietrich, Philipp A; Yang, Chen; Leung, Halina H L; Lynch, Jennifer R; Gonzales, Estrella; Liu, Bing; Haber, Michelle; Norris, Murray D; Wang, Jianlong; Wang, Jenny Yingzi

    2014-11-20

    β-catenin is required for establishment of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). Targeted inhibition of β-catenin signaling has been hampered by the lack of pathway components amenable to pharmacologic manipulation. Here we identified a novel β-catenin regulator, GPR84, a member of the G protein-coupled receptor family that represents a highly tractable class of drug targets. High GPR84 expression levels were confirmed in human and mouse AML LSCs compared with hematopoietic stem cells (HSCs). Suppression of GPR84 significantly inhibited cell growth by inducing G1-phase cell-cycle arrest in pre-LSCs, reduced LSC frequency, and impaired reconstitution of stem cell-derived mixed-lineage leukemia (MLL) AML, which represents an aggressive and drug-resistant subtype of AML. The GPR84-deficient phenotype in established AML could be rescued by expression of constitutively active β-catenin. Furthermore, GPR84 conferred a growth advantage to Hoxa9/Meis1a-transduced stem cells. Microarray analysis demonstrated that GPR84 significantly upregulated a small set of MLL-fusion targets and β-catenin coeffectors, and downregulated a hematopoietic cell-cycle inhibitor. Altogether, our data reveal a previously unrecognized role of GPR84 in maintaining fully developed AML by sustaining aberrant β-catenin signaling in LSCs, and suggest that targeting the oncogenic GPR84/β-catenin signaling axis may represent a novel therapeutic strategy for AML. © 2014 by The American Society of Hematology.

  17. Effect of pentoxifylline on P-glycoprotein mediated vincristine resistance of L1210 mouse leukemic cell line

    International Nuclear Information System (INIS)

    Breier, A.; Uhrik, B.; Barancik, M.; Stefankova, Z.; Tribulova, N.

    1994-01-01

    Effect of pentoxifylline (PTX) on vincristine (VCR) resistance of multidrug resistant L1210/VCR mouse leukemic cell line was studied. Reversal effect of PTX (in concentration 50-150 mg dm -3 ) on vincristine resistance, i.e. potentiation of vincristine cytotoxicity on L1210/VCR cells by PTX was found. PTX alone in the above concentration did not exert any significant effect on sensitive or resistant cell lines in the absence of vincristine. Resistance of L1210/VCR cell line was found previously to be accompanied with overexpression of drug transporting P-glycoprotein. Indeed, lower level of 3 H-vincristine accumulation by resistant L1210/VCR cell line in comparison with sensitive L1210 cell line was observed. Accumulation of 3 H-vincristine by L1210/VCR cell line was significantly increased in the presence of PTX. PTX in the same condition did not exert any considerable effect on accumulation of 3 H-vincristine by nonresistant L1210 cells. Observable morphological damage was observed in 1210/VCR cells cultivated in medium containing vincristine (0.2 mg dm -3 ) and pentoxifylline (100 mg dm -3 ) in comparison with the non-damaged cells in the presence of vincristine or pentoxifylline alone. The results obtained indicate that pentoxifylline may be considered as a reversal agent in multidrug resistance. (author)

  18. Delayed expression of apoptosis in X-irradiated human leukemic MOLT-4 cells transfected with mutant p53

    International Nuclear Information System (INIS)

    Nakano, Hisako; Yonekawa, Hiromichi; Shinohara, Kunio

    2003-01-01

    The effects of X-rays on cell survival, apoptosis, and long-term response in the development of cell death as measured by the dye exclusion test were studied in human leukemic MOLT-4 cells (p53 wild-type) stably transfected with a mutant p53 cDNA expression vector. Cell survival, as determined from colony-forming ability, was increased in an expression level dependent manner, but the increase was partial even with the highest-expressing clone (B3). This contrasts with the prior observation that cell death and apoptosis in B3 are completely inhibited at 24 h after irradiation with 1.8 Gy of X-rays. The examination of B3 cells incubated for longer than 24 h after X-irradiation showed a delay in the induction of cell death and apoptosis. Western blot analysis revealed that the time required to reach the highest level of wild-type p53 protein in B3 was longer than the time in MOLT-4 and that the p53 may be stabilized by the phosphorylation at Ser-15. These results suggest that the introduction of mutant p53 into MOLT-4 merely delays the development of apoptosis, during which the cells could repair the damage induced by X-rays, and results in the partial increase in cell survival. (author)

  19. Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540

    Energy Technology Data Exchange (ETDEWEB)

    Porcellini, A.; Talevi, N.; Marchetti-Rossi, M.T.; Palazzi, M.; Manna, A.; Sparaventi, G.; Delfini, C.; Valentini, M.

    1987-11-01

    To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.

  20. Lack of correlation between immunologic markers and cell surface ultrastructure in the leukemic phase of lymphoproliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, Harvey M.; Simon, Deberah

    1977-01-01

    In a prospective study of malignant cells from 13 patients with the leukemic phase of lymphoproliferative diseases, we wished to determine whether any correlation between the immunologic markers and the cell surface ultrastructure. Five patients had chronic lymphocytic leukemia, four had malignant lymphomas, poorly differentiated lymphocytic type, two had the Sezary syndrome, and one each had acute prolymphocytic leukemia and acute lymphocytic leukemia. Cell separation and isolation was done at room temperature for all specimens. Immunologic markers tested for were surface immunoglobins, a B-cell property, and E-rosettes, a T-cell property. Three patients had T-cell diseases, 6 had B-cell diseases, and 4 were classified as ''null.'' All but one patient had moderate to large numbers of microvilli on their malignant cells. The single exception had a typical B-cell form of chronic lymphocytic leukemia. There appears to be no correlation between immunologic markers and cell surface ultrastructure; therefore, SEM appears not to be valuable in the diagnosis or classification of immunologic sub-types of certain lymphoproliferative diseases.

  1. F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation

    Science.gov (United States)

    Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Zou, Chunbin; Miller, Hannah L.; Fenton, Moon; McDyer, John F.; Boyiadzis, Michael

    2012-01-01

    Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G0 phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCFFBXL2 in lymphoproliferative malignancies. PMID:22323446

  2. Pulmonary leukemic involvement: high-resolution computed tomography evaluation; Comprometimento pulmonar nas leucemias: avaliacao por tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ana Paola de [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Programa de Pos-graduacao em Radiologia; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Souza, Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Radiologia

    2004-12-01

    Objective: To evaluate the role of high-resolution computed tomography (HRCT) in patients with leukemia and pulmonary symptoms, to establish the main patterns and to correlate them with the etiology. Materials and Methods: This is a retrospective study of the HRCT of 15 patients with leukemia and pulmonary symptoms. The examinations were performed using a spatial high-resolution protocol and were analyzed by two independent radiologists. Results: The main HRCT patterns found were ground-glass opacity (n=11), consolidation (n=9), airspace nodules (n=3), septal thickening (n=3), tree-in-bud pattern (n=3), and pleural effusion (n=3). Pulmonary infection was the most common finding seen in 12 patients: bacterial pneumonia (n=6), fungal infection (n = 4), pulmonary tuberculosis (n=1) and viral infection (n=1). Leukemic pleural infiltration (n=1), lymphoma (n=1) and pulmonary hemorrhage (n=1) were detected in the other three patients. Conclusion: HRCT is an important tool that may suggest the cause of lung involvement, its extension and in some cases to guide invasive procedures in patients with leukemia. (author)

  3. Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID Mouse In Vivo

    Directory of Open Access Journals (Sweden)

    Ryosuke Shirasaki

    2012-01-01

    Full Text Available We recently reported that chronic myelogenous leukemia (CML cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.

  4. To the nucleolar density and size in apoptotic human leukemic myeloblasts produced in vitro by Trichostatin A

    Directory of Open Access Journals (Sweden)

    K Smetana

    2009-08-01

    Full Text Available The present study was designed to provide more information on nucleoli in apoptotic cells, which were represented in the present study by cultured leukemic myeloblasts (Kasumi-1 cells. The apoptotic process in these cells was produced by trichostatin A (TSA that is a histone deacetylase inhibitor with strong cytostatic effects. The selected TSA concentration added to cultures facilitated to study apoptotic and notapoptotic cells in one and the same specimen. The nucleolar diameter and density were determined using computer assisted measurement and densitometry in specimens stained for RNA. In comparison with not-apoptotic cells, in apoptotic cells, nucleolar mean diameter did not change significantly and nucleolar RNA density was also not apparently different. On the other hand, the cytoplasmic RNA density in apoptotic cells was markedly reduced. Thus it seemed to be possible that the transcribed RNA remained “frozen” within the nucleolus but its transport to the cytoplasm decreased or stopped. However, the possibility of the RNA degradation in the cytoplasm of apoptotic cells based on the present study cannot be eliminated. At this occasion it should be added that AgNORs reflecting nucleolar biosynthetic and cell proliferation activity in apoptotic cells decreased in number or disappeared. The presented results also indicated that large nucleoli intensely stained for RNA need not be necessarily related to the high nucleolar biosynthetic or cell proliferation activity and may be also present in apoptotic cells responding to the cytostatic treatment.

  5. Oxidative damage of U937 human leukemic cells caused by hydroxyl radical results in singlet oxygen formation.

    Directory of Open Access Journals (Sweden)

    Marek Rác

    Full Text Available The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.

  6. House dust mite induces expression of intercellular adhesion molecule-1 in EoL-1 human eosinophilic leukemic cells.

    Science.gov (United States)

    Kwon, Byoung Chul; Sohn, Myung Hyun; Kim, Kyung Won; Kim, Eun Soo; Kim, Kyu-Earn; Shin, Myeong Heon

    2007-10-01

    The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF-kappaB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF-kappaB and JNK.

  7. Effects of vinegar–egg on growth inhibition, differentiation human leukemic U937 cells and its immunomodulatory activity

    Directory of Open Access Journals (Sweden)

    Shiu-Yu Wang

    2018-04-01

    Full Text Available Vinegar and eggs have rich nutrients. In this study, the mixed form of both derived products, vinegar–egg solution and its products (vinegar–egg concentrate and vinegar–egg condensate were chosen for an assessment of their biological activity. To further our understanding regarding the anticancer and immunomodulatory effects of vinegar–egg, we investigated its effects on the proliferation and differentiation of U937 cells. Vinegar–egg was treated using spray drying, freeze drying and vacuum concentration and used to stimulate human mononuclear cells. The conditioned media obtained from these cultures by filtration were used to treat U937 cells. Three conditioned media inhibited U937 cell growth by 22.1–67.25% more effectively than PHA-treated control (22.53%. CD11b and CD14 expression on the treated U937 cells were 29.1–45.4% and 31.6–47.2%, respectively. High levels of cytokines IL-1β, IFN-γ and TNF-α were detected in the three conditioned media. Vinegar–egg stimulates human mononuclear cells to secrete cytokines, which inhibit the growth of U937 cells and induce their differentiation. Keywords: Cytokines, Differentiation, Immunomodulatory activity, Leukemic U937 cells, Vinegar–egg

  8. Effects of in vitro Brevetoxin Exposure on Apoptosis and Cellular Metabolism in a Leukemic T Cell Line (Jurkat

    Directory of Open Access Journals (Sweden)

    John W. Sleasman

    2008-06-01

    Full Text Available Harmful algal blooms (HABs of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl-3,5- diphenylformazan, respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 - 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3.

  9. Genomic Profiling of a Human Leukemic Monocytic Cell-Line (THP-1 Exposed to Alpha Particle Radiation

    Directory of Open Access Journals (Sweden)

    Vinita Chauhan

    2012-01-01

    Full Text Available This study examined alpha (α- particle radiation effects on global changes in gene expression in human leukemic monocytic cells (THP-1 for the purposes of mining for candidate biomarkers that could be used for the development of a biological assessment tool. THP-1 cells were exposed to α-particle radiation at a dose range of 0 to 1.5 Gy. Twenty-four hours and three days after exposure gene expression was monitored using microarray technology. A total of 16 genes were dose responsive and classified as early onset due to their expression 24 h after exposure. Forty-eight transcripts were dose responsive and classified as late-onset as they were expressed 72 h after exposure. Among these genes, 6 genes were time and dose responsive and validated further using alternate technology. These transcripts were upregulated and associated with biological processes related to immune function, organelle stability and cell signalling/communication. This panel of genes merits further validation to determine if they are strong candidate biomarkers indicative of α-particle exposure.

  10. Preliminary Study on Bidding Price Ratio Pattern of Public Works in Taiwan - a Case Study of Bridges, Elevated Highways, Tunnels and Subways

    Science.gov (United States)

    Tseng, Paoshan; Wang, Hanhsiang; Chen, Pingfu; Yeh, Lihsu

    2018-01-01

    Commonly seen tender bid price information of the public works in Taiwan are the budget amount, floor price, awarding price and so on. The ratio of the awarding price to the floor price or budget price is the so-called bidding price ratio. This ratio is influenced by multifaceted factor interactions and is significant to decision making management in engineering projects. Low bidding price ratio may imply that the budget allocation by the tendering agency is inconsiderate or due to the improper market competition of low price bid rigging. High bidding price ratio in turn may indicate that the allocated budget is relatively low, bidder risks in increased contract execution uncertainty or even exclusive bidding scenario. Therefore, the correlation between the bidding price ratio and the aforementioned tender award information is the key issue of this study. This study gathered the tender information of the civil engineering projects in Taiwan within the past seven years. By performing statistical analysis and clustering the gathered data by bidding price ratio, this study investigated the influencing factors and regulations of bidding price ratio using data mining approach.

  11. The System of Public Acquisitions by Means of Electronic Bids in the Light of European Regulations

    Directory of Open Access Journals (Sweden)

    Costantin Roman

    2007-01-01

    Full Text Available E-commerce can lead in many different ways to cost reduction in case of a supplier and can subsequently increase the competition potential of a company. As for the competition mechanism, such changes produce significant modifications within a market economy. The Internet renders the possibility of creating business contacts in a rapid and geographically independent manner, as well as possibilities of obtaining data and realizing transactions within the world’s economy. Public acquisitions by means of dynamic systems and electronic bids are currently one of the significant areas of electronic commerce.

  12. Calibration of short rate term structure models from bid-ask coupon bond prices

    Science.gov (United States)

    Gomes-Gonçalves, Erika; Gzyl, Henryk; Mayoral, Silvia

    2018-02-01

    In this work we use the method of maximum entropy in the mean to provide a model free, non-parametric methodology that uses only market data to provide the prices of the zero coupon bonds, and then, a term structure of the short rates. The data used consists of the prices of the bid-ask ranges of a few coupon bonds quoted in the market. The prices of the zero coupon bonds obtained in the first stage, are then used as input to solve a recursive set of equations to determine a binomial recombinant model of the short term structure of the interest rates.

  13. A bid solicitation and selection method for developing a competitive spot priced electric market

    International Nuclear Information System (INIS)

    Ancona, J.J.

    1997-01-01

    The electric utility industry is in the beginning throes of a transformation from a cost-based regulated structure to a more market based less regulated system. Traditional unit commitment and economic dispatch methodologies can continue to provide reliable least-cost solutions, providing they are modified to accommodate a larger sphere of market participants. This paper offers a method for an entity such as an Independent System Operator (ISO) to solicit and evaluate bids for developing a spot priced electric market by replicating existing utility practices that are effective and efficient, while creating an open and equitable competitive marketplace for electricity

  14. G-Doob-Meyer Decomposition and Its Applications in Bid-Ask Pricing for Derivatives under Knightian Uncertainty

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2015-01-01

    Full Text Available The target of this paper is to establish the bid-ask pricing framework for the American contingent claims against risky assets with G-asset price systems on the financial market under Knightian uncertainty. First, we prove G-Dooby-Meyer decomposition for G-supermartingale. Furthermore, we consider bid-ask pricing American contingent claims under Knightian uncertainty, by using G-Dooby-Meyer decomposition; we construct dynamic superhedge strategies for the optimal stopping problem and prove that the value functions of the optimal stopping problems are the bid and ask prices of the American contingent claims under Knightian uncertainty. Finally, we consider a free boundary problem, prove the strong solution existence of the free boundary problem, and derive that the value function of the optimal stopping problem is equivalent to the strong solution to the free boundary problem.

  15. The effect of electric transmission constraints on how power generation companies bid in the Colombian electrical power market

    Directory of Open Access Journals (Sweden)

    Luis Eduardo Gallego Vega

    2010-05-01

    Full Text Available This paper presents the results of research about the effect of transmission constraints on both expected electrical energy to be dispatched and power generation companies’ bidding strategies in the Colombian electrical power market. The proposed model simulates the national transmission grid and economic dispatch by means of optimal power flows. The proposed methodology allows structural problems in the power market to be analyzed due to the exclusive effect of trans- mission constraints and the mixed effect of bidding strategies and transmission networks. A new set of variables is proposed for quantifying the impact of each generation company on system operating costs and the change in expected dispatched energy. A correlation analysis of these new variables is presented, revealing some interesting linearities in some generation companies’ bidding patterns.

  16. Improving Agent Bidding in Power Stock Markets through a Data Mining Enhanced Agent Platform

    Science.gov (United States)

    Chrysopoulos, Anthony C.; Symeonidis, Andreas L.; Mitkas, Pericles A.

    Like in any other auctioning environment, entities participating in Power Stock Markets have to compete against other in order to maximize own revenue. Towards the satisfaction of their goal, these entities (agents - human or software ones) may adopt different types of strategies - from na?ve to extremely complex ones - in order to identify the most profitable goods compilation, the appropriate price to buy or sell etc, always under time pressure and auction environment constraints. Decisions become even more difficult to make in case one takes the vast volumes of historical data available into account: goods’ prices, market fluctuations, bidding habits and buying opportunities. Within the context of this paper we present Cassandra, a multi-agent platform that exploits data mining, in order to extract efficient models for predicting Power Settlement prices and Power Load values in typical Day-ahead Power markets. The functionality of Cassandra is discussed, while focus is given on the bidding mechanism of Cassandra’s agents, and the way data mining analysis is performed in order to generate the optimal forecasting models. Cassandra has been tested in a real-world scenario, with data derived from the Greek Energy Stock market.

  17. Self-scheduling and bidding strategies of thermal units with stochastic emission constraints

    International Nuclear Information System (INIS)

    Laia, R.; Pousinho, H.M.I.; Melíco, R.; Mendes, V.M.F.

    2015-01-01

    Highlights: • The management of thermal power plants is considered for different emission allowance levels. • The uncertainty on electricity price is considered by a set of scenarios. • A stochastic MILP approach allows devising the bidding strategies and hedging against price uncertainty and emission allowances. - Abstract: This paper is on the self-scheduling problem for a thermal power producer taking part in a pool-based electricity market as a price-taker, having bilateral contracts and emission-constrained. An approach based on stochastic mixed-integer linear programming approach is proposed for solving the self-scheduling problem. Uncertainty regarding electricity price is considered through a set of scenarios computed by simulation and scenario-reduction. Thermal units are modelled by variable costs, start-up costs and technical operating constraints, such as: forbidden operating zones, ramp up/down limits and minimum up/down time limits. A requirement on emission allowances to mitigate carbon footprint is modelled by a stochastic constraint. Supply functions for different emission allowance levels are accessed in order to establish the optimal bidding strategy. A case study is presented to illustrate the usefulness and the proficiency of the proposed approach in supporting biding strategies

  18. BID-ASK SPREAD DAN PERIODE KEPEMILIKAN SAHAM PADA PERUSAHAAN LQ-45

    Directory of Open Access Journals (Sweden)

    Vinus Maulina

    2011-10-01

    Full Text Available Global crisis gives quite big impact to the Indonesian Stock Exchange and also changes the investor behavior as well. Fundamental exchange which is considered fragile becomes instability threat and reflects uncertain condition. This research aims to analyze and explain empirically the impact of variance return, trading volume, stock prices and return shares toward bid-ask spread which is the measurement of asymmetrical information cost, also the impact of variance return, market value, bid-ask spread and dividend pay out towards common shares holding periods in Indonesia Stock Exchange and some dominant variable that affect them.The findings of this research strengthen the presumption that in conducting the investment, investors in Indonesian Stock Exchange is more oriented to short term investment by expecting more on common shares than dividend. Most investors keep their ownership in common shares in Indonesian Stock Exchange for two years. Besides, the efficient investment strategy which optimizes profit is “switching strategy”, following the market movement every time exactly, using technical information to active shares by moving from the shares that the price is predicted to decline to the increased ones. Moreover, the researcher also got the evidence that the investors in Indonesian capital market conduct their investment irrationally, investor’s analysis is getting technical and gives less attention to the fundamental factors. The decision of selling and buying which is conducted by the investors on common shares is based on the trading activity, that is actually a measurement of the scale of asymmetry information.

  19. Cnooc's fourth bidding round offers first tracts in East China Sea

    International Nuclear Information System (INIS)

    Ganapathy, V.

    1992-01-01

    This paper reports that China National Offshore Oil Corp. (Cnooc) has unveiled details of China's fourth offshore bidding round. It features the first offering of acreage in the East China Sea. Cnooc, China's state agency for offshore oil cooperation with foreign firms, has sweetened fiscal and tax terms for operators in the fourth round, announced June 30 (OGJ, July 6, Newsletter). Cnooc put up for bids two groups of acreage in the East China Sea that cover a total area of almost 73,000 sq km. The northern acreage, consisting of four blocks, covers 18,800 sq km and is 230 km east of Shanghai. The southern acreage, consisting of 16 blocks, covers 54,000 sq km and is 110 km east of Wenzhou, Zhejiang province. The area waters are 50-100 m deep and relatively calm year round. Chines explorationists have conducted 60,000 line km of seismic surveys and drilled five wildcats in the two areas, Data indicate the two areas have thick sediments, good source rocks, and strong conditions for oil traps

  20. Does Bid/Ask Spread React to the Increase of Internet Search Traffic?

    Directory of Open Access Journals (Sweden)

    Ridwan Nurazi

    2015-12-01

    Full Text Available This article solely examines the effect of investor attentions on bid-ask spread. We find that investors’ attention surrogated by Internet Search Traffic (IST contribute positively and significantly toward bid-ask spread (SPREAD. This result indicates that the incoming information directs the market within the stack circumstance and thin trading activity. Here, our samples were obtained from the manufacturing index, in the Indonesia Stock Exchange (IDX during the period of observation ranging from 2009 to 2011. The hypothesis testing in this research is performed by using panel data regression analysis (Fixed Effect Model. Test result reveals that the search of online information through Google is beneficially one of the efforts to reduce asymmetry information between informed investors and uninformed investors. Besides, we also note that asymmetric information not only exists between the informed and uninformed investors, but also happens to market makers and informed investors. Finally, our findings lead to a conclusion, in which the high search of information tends to help investors in making appropriate investment decisions.

  1. Use of multi-criteria decision analysis in public bidding processes: a case study

    Directory of Open Access Journals (Sweden)

    André Andrade Longaray

    2014-02-01

    Full Text Available Institutions of Higher Education in Brazil (IFES play an important role in the country’s social and scientific development. Focused mainly on teaching, research and extension activities, the IFES are backed by support foundations aimed to the management of financial, human and material resources. Characterized as public bodies, the support foundations are governed by Law no 8.666/93 in what concerns the procurement of goods and services. Therefore, the present study is aimed to develop a model to assist the managers of such foundations in the selection of suppliers to participate in bidding processes that use invitation for bids. Therefore, we conducted a case study in one of the 55 foundations that support Brazilian federal universities. The intervention tool used was the Analytic Hierarchy Process (AHP. Firstly, we established the hierarchy of criteria for problem-solving. Then, a paired comparison was made between criteria for the same level. Subsequently, the consistency analysis of comparison matrices was verified. Finally, the relative priorities of each criterion were obtained and the objective function of the model was constructed. The model was tested through the assessment of the performance of three potential suppliers of IT equipment, and the result was legitimized by decision makers who found the instrument a valid tool to aid in making decisions on supplier selection for the foundation.

  2. Application of Q-learning with temperature variation for bidding strategies in market based power systems

    International Nuclear Information System (INIS)

    Naghibi-Sistani, M.B.; Akbarzadeh-Tootoonchi, M.R.; Javidi-Dashte Bayaz, M.H.; Rajabi-Mashhadi, H.

    2006-01-01

    The electric power industry is confronted with restructuring in which the operation scheduling is going to be decided based on a competitive market. In this new arrangement, bidding strategy has become a major issue. Participants in this deregulated energy market place may be able to compete better by choosing a suitable bidding strategy for trading electricity. Different classical methods for decision making in the uncertain environment of the market can be applied to select a suitable strategy. Most of these methods, such as game theory, that insure reaching the best solution for all market participants, require a lot of information about the other market players and the market. However, in the real market place only a little information, such as the spot price, is available for all participants. In this paper, a modified reinforcement learning based on temperature variation has been first proposed and then applied to determine the optimal strategy for a power supplier in the electricity market. A Pool-Co model has been considered here, and the simulation results are shown to be the same as those of standard game theory. Adaptation of the method in the presence of parameter variation has been verified as well. The main advantage of the proposed method is that no information about other participants is required. Furthermore, our investigation shows that even if all participants use this method, they will stay in Nash equilibrium. (author)

  3. Bidding cost evaluation with fuzzy methods on building project in Jakarta

    Science.gov (United States)

    Susetyo, Budi; Utami, Tin Budi

    2017-11-01

    National construction companies today demanded to become more competitive to face increasingly competition. Every construction company especially the contractor must work better than ever. Ability to prepare cost of the work that represents the efficiency and effectiveness of the implementation of the work necessary to produce cost - competitive. The project is considered successful if the target meets the quality, cost and time. From the aspect of cost, the project has been designed in accordance with certain technical criteria to be taken into account based on standard costs. To ensure the cost efficiency of the bidding process carried out meet the rules of a fairly and competitive. The research objective is to formulate the proper way to compare several deals with the standard cost of the work. The fuzzy technique is used as a evaluation methods to decision making. The evaluation not merely based on the lowest prices. The methods is looking for the most valuable and reasonable prices. The comparison is conducted to determine the most cost-competitive and reasonable as the winner of the bidding.

  4. Generators' bidding behavior in the NYISO day-ahead wholesale electricity market

    International Nuclear Information System (INIS)

    Zhang, Ning

    2009-01-01

    This paper proposes a statistical and econometric model to analyze the generators' bidding behavior in the NYISO day-ahead wholesale electricity market. The generator level bidding data show very strong persistence in generators' grouping choices over time. Using dynamic random effect ordered probit model, we find that persistence is characterized by positive state dependence and unobserved heterogeneity and state dependence is more important than unobserved heterogeneity. The finding of true state dependence suggests a scope for economic policy intervention. If NYISO can implement an effective policy to switch generators from higher price groups to lower price groups, the effect is likely to be lasting. As a result, the market price can be lowered in the long-run. Generators' offered capacity is estimated by a two-stage sample selection model. The estimated results show that generators in higher-priced groups tend to withhold their capacity strategically to push up market prices. It further confirms the importance of an effective policy to turn generators into lower price groups in order to mitigate unexpected price spikes. The simulated market prices based on our estimated aggregate supply curve can replicate most volatility of actual DA market prices. Applying our models to different demand assumptions, we find that demand conditions can affect market prices significantly. It validates the importance of introducing demand side management during the restructure of electricity industry. (author)

  5. New approach to bidding strategies of generating companies in day ahead energy market

    International Nuclear Information System (INIS)

    Soleymani, S.; Ranjbar, A.M.; Shirani, A.R.

    2008-01-01

    In the restructured power systems, generating companies (Genco) are responsible for selling their product in the energy market. In this condition, the question is how much and for what price must each Genco generate to maximize its profit. Therefore, this paper intends to propose a rational method to answer this question. In the proposed methodology, the hourly forecasted market clearing price (FMCP) is used as a reference to model the possible and probable price strategies of Gencos. The forecasted price is the basis of the bidding strategies of each Genco, which can be achieved by solving a bi-level optimization problem using GAMS (general algebraic modeling system) language. The first level, called upper sub-problem is used to maximize the individual Genco's payoffs for obtaining the optimal offered quantity of Gencos. The second one, hereafter called the lower sub-problem uses the results of the upper sub-problem and minimizes the consumer's payment with regard to the technical and network constraints, which leads to the awarded generation of the Gencos. Similar to the other game problems, the Nash equilibrium strategies are the optimum bidding strategies of Gencos. A six bus system is employed to illustrate the application of the proposed method and to show its high precision and capabilities. (author)

  6. Using and comparing metaheuristic algorithms for optimizing bidding strategy viewpoint of profit maximization of generators

    Science.gov (United States)

    Mousavi, Seyed Hosein; Nazemi, Ali; Hafezalkotob, Ashkan

    2015-03-01

    With the formation of the competitive electricity markets in the world, optimization of bidding strategies has become one of the main discussions in studies related to market designing. Market design is challenged by multiple objectives that need to be satisfied. The solution of those multi-objective problems is searched often over the combined strategy space, and thus requires the simultaneous optimization of multiple parameters. The problem is formulated analytically using the Nash equilibrium concept for games composed of large numbers of players having discrete and large strategy spaces. The solution methodology is based on a characterization of Nash equilibrium in terms of minima of a function and relies on a metaheuristic optimization approach to find these minima. This paper presents some metaheuristic algorithms to simulate how generators bid in the spot electricity market viewpoint of their profit maximization according to the other generators' strategies, such as genetic algorithm (GA), simulated annealing (SA) and hybrid simulated annealing genetic algorithm (HSAGA) and compares their results. As both GA and SA are generic search methods, HSAGA is also a generic search method. The model based on the actual data is implemented in a peak hour of Tehran's wholesale spot market in 2012. The results of the simulations show that GA outperforms SA and HSAGA on computing time, number of function evaluation and computing stability, as well as the results of calculated Nash equilibriums by GA are less various and different from each other than the other algorithms.

  7. Detection of Ca2+-induced acetylcholine released from leukemic T-cells using an amperometric microfluidic sensor.

    Science.gov (United States)

    Akhtar, Mahmood H; Hussain, Khalil K; Gurudatt, N G; Shim, Yoon-Bo

    2017-12-15

    A microfluidic structured-dual electrodes sensor comprising of a pair of screen printed carbon electrodes was fabricated to detect acetylcholine, where one of them was used for an enzyme reaction and another for a detection electrode. The former was coated with gold nanoparticles and the latter with a porous gold layer, followed by electropolymerization of 2, 2:5,2-terthiophene-3-(p-benzoic acid) (pTTBA) on both the electrodes. Then, acetylcholinesterase was covalently attached onto the reaction electrode, and hydrazine and choline oxidase were co-immobilized on the detection electrode. The layers of both modified electrodes were characterized employing voltammetry, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and quartz crystal microscopy. After the modifications of both electrode surfaces, they were precisely faced each other to form a microfluidic channel structure, where H 2 O 2 produced from the sequential enzymatic reactions was reduced by hydrazine to obtain the analytical signal which was analyzed by the detection electrode. The microfluidic sensor at the optimized experimental conditions exhibited a wide dynamic range from 0.7nM to 1500μM with the detection limit of 0.6 ± 0.1nM based on 3s (S/N = 3). The biomedical application of the proposed sensor was evaluated by detecting acetylcholine in human plasma samples. Moreover, the Ca 2+ -induced acetylcholine released in leukemic T-cells was also investigated to show the in vitro detection ability of the designed microfluidic sensor. Interference due to the real component matrix were also studied and long term stability of the designed sensor was evaluated. The analytical performance of the designed sensor was also compared with commercially available ACh detection kit. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Detection of a novel specificity (CTLA-4) in ATG/TMG globulins and sera from ATG-treated leukemic patients.

    Science.gov (United States)

    Pistillo, Maria Pia; Tazzari, Pier Luigi; Bonifazi, Francesca; Bandini, Giuseppe; Kato, Tomohiro; Matsui, Toshihiro; Nishioka, Kusuki; Conte, Roberto; Ferrara, Giovanni Battista

    2002-04-27

    T-cell costimulation has been shown to provide positive signals for T-cell activation and generation of effector activity. In this study, we analyzed the presence of antibodies (Abs) against the T-lymphocyte costimulatory molecules CD28, CTLA-4, CD80, and CD86 in anti-T-lymphocyte (ATG) and antithymocyte (TMG) globulin preparations to address their mechanism of action. We focused our attention on the role of CTLA-4-specific Abs in the immunosuppressive effect of ATG/TMG, because anti-CTLA-4 agonistic Abs may suppress T-cell proliferation and nonagonistic Abs may lead to T-cell depletion through an Ab-dependent cell cytotoxicity mechanism. ATG/TMG and patients' sera were tested for binding to recombinant human costimulatory molecules by ELISA techniques. CTLA-4 specificity was also analyzed by cytoplasmic immunofluorescence staining of a CTLA-4 transfectant by competitive inhibition immunofluorescence and by cell proliferation assay in allogeneic mixed lymphocyte reaction (MLR). Either ATG or TMG predominantly contained anti-CTLA-4 Abs, with higher reactivity in ATG followed by anti-CD86 and -CD28 Abs, whereas anti-CD80 Abs were found only in ATG. Anti-CTLA-4 Abs present in ATG/TMG recognized the native form of CTLA-4 molecule, and their removal reduced the effect of ATG in an allogeneic MLR. Kinetic studies indicated that such Abs were present in the sera of 12 ATG-treated leukemic patients up to 21 days after ATG administration. These data suggest that the novel anti-CTLA-4 Abs found in ATG may greatly contribute to its immunosuppressive effect, thus accounting for the absence of rejection and exceptionally low incidence of graft-versus-host disease in the group of patients analyzed.

  9. Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol

    International Nuclear Information System (INIS)

    Arora, Annu; Seth, Kavita; Kalra, Neetu; Shukla, Yogeshwer

    2005-01-01

    Resistance to chemotherapeutic drugs is one of the major problems in the treatment of cancer. P-glycoprotein (P-gp) encoded by the mdr gene is a highly conserved protein, acts as a multidrug transporter, and has a major role in multiple drug resistance (MDR). Targeting of P-gp by naturally occurring compounds is an effective strategy to overcome MDR. Indole-3-carbinol (I3C), a glucosinolates present in cruciferous vegetables, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic, and antiestrogenic properties in experimental studies. In the present investigation, the potential of I3C to modulate P-gp expression was evaluated in vinblastine (VBL)-resistant K562 human leukemic cells. The resistant K562 cells (K562/R10) were found to be cross-resistant to vincristine (VCR), doxorubicin (DXR), and other antineoplastic agents. I3C at a nontoxic dose (10 x 10 -3 M) enhanced the cytotoxic effects of VBL time dependently in VBL-resistant human leukemia (K562/R10) cells but had no effect on parent-sensitive cells (K562/S). The Western blot analysis of K 562/R 10 cells showed that I3C downregulates the induced levels of P-gp in resistant cells near to normal levels. The quantitation of immunocytochemically stained K562/R10 cells showed 24%, 48%, and 80% decrease in the levels of P-gp by I3C for 24, 48, and 72 h of incubation. The above features thus indicate that I3C could be used as a novel modulator of P-gp-mediated multidrug resistance in vitro and may be effective as a dietary adjuvant in the treatment of MDR cancers

  10. Documentation of normal and leukemic myelopoietic progenitor cells with high-resolution phase-contrast time-lapse cinematography.

    Science.gov (United States)

    Boll, I T

    2001-08-01

    The high-resolution phase-contrast, time-lapse cinematography using oil immersion lenses and 16-mm film demonstrates the kinetic cell events as maturation, locomotion, mitosis, and apoptosis of cells cultivated at 37 degrees C for up to 10 days. 0.5 v/v frozen-thawed sera with presumably high cytokine concentrations were added to the plasma or agar clot. Vital progenitor cells from human bone marrow and blood have a large, bright, unstructured nucleus with a large nucleolus and a narrow rim of cytoplasm (nuclear/cytoplasmic volume ratio = 0.7). Their nuclei are 6-14 micrometer in diameter and double their volume within 8 h. Many (70%) move at a mean speed of 2 micrometer/min, and many (30%) multiply with alpha-2alpha mitoses, generating progenitor cell families. Various disturbances during the course of mitosis lead to the formation of polyploid cells, thereby yielding the megakaryocytic cell line. Some of the progenitor cells undergo asymmetric alpha-alphan mitoses: One of the two initially identical daughter cells remains a progenitor cell in the morphological sense, whereas the other daughter cell - depending on the size of its mother cell - matures in the same culture medium to form a granulocytopoietic, monocytopoietic or erythrocytopoietic cell line. - In acute myeloid leukemias (AML), the blasts and their nuclei are slightly larger than the corresponding progenitor cells and move faster (5 micrometer/min). Symmetric alpha-2alpha mitoses permit unlimited multiplication of the leukemic blasts if contact with cytotoxic lymphocytes does not render them apoptotic. This results in more stromal cells than normal. Granulocytopenia, monocytopenia, and anemia occur due to the genetic impairment of signaling control for asymmetric alpha-alphan mitoses, and thrombocytopenia occurs due to the reduction in polyploidization. Copyright 2001 S. Karger GmbH, Freiburg

  11. PURIFICATION AND FRACTIONAL ANALYSIS OF METHANOLIC EXTRACT OF WEDELIA TRILOBATA POSSESSING APOPTOTIC AND ANTI-LEUKEMIC ACTIVITY

    Science.gov (United States)

    Venkatesh, Uday; Javarasetty, Chethan; Murari, Satish Kumar

    2017-01-01

    Background: Wedelia trilobata (L.) Hitch (WT), commonly known as yellow dots or creeping daisy, is a shrub possessing potent biological activities, and is traditionally used a medicinal plant in Ayurveda, Siddha and Unani systems of medicines, and it has also been tried against leukemia cell line MEG- 01. In the present study, purification and screening of the plant was done for bioactive compounds in methanolic extract of WT for apoptotic and anti-leukemia activity. Materials and methods: The methanolic extract of WT was initially purified through thin layer chromatography (TLC) and screened for the apoptotic and anti-leukemia activities. The positive band of TLC was subjected to silica gel column chromatography for further purification and the fractions obtained from it were screened again for anti-leukemia activity through thymidine uptake assay and apoptotic activity by DNA fragmentation, nuclear staining and flow cytometry assays. The fraction with positive result was subjected to HPLC for analysis of bioactive components. Results: Out of many combinations of solvents, the methanol and dichloromethane combination in the ratio 6:4 has revealed two bands in TLC, among which the second band showed positive results for apoptotic and anti-leukemic activities. Further purification of second band through silica gel chromatography gave five fractions in which the 3rd fraction gave positive results and it shows single peak during compositional analysis through HPLC. Conclusion: The single peak revealed through HPLC indicates the presence of pure compound with apoptotic and anti-leukemia activities encouraging for further structural analysis. PMID:28480428

  12. A critical Analysis of Bidding Exemption and Unenforceability – In Search of a Theory that Allows the Application in Specific Cases

    Directory of Open Access Journals (Sweden)

    Felipe Cesar Lapa Boselli

    2016-10-01

    Full Text Available The paper aims to conduct a review of the legislation, doctrine and jurisprudence about the possibilities of public hiring without bidding, working on a theory for division of existing institutes and applying this theory in the central hypothesis of the article that it would be illegal to emergency hiring continuous service through the bidding process.

  13. Varying the number of bidders in the first-price sealed-bid auction: experimental evidence for the one-shot game

    NARCIS (Netherlands)

    Füllbrunn, S.C.; Neugebauer, T.

    2013-01-01

    The paper reports experimental data on the behavior in the first-price sealed-bid auction for a varying number of bidders when values and bids are private information. This feedback-free design is proposed for the experimental test of the one-shot game situation. We consider both within-subjects and

  14. 31 CFR 351.10 - What do I need to know about market yields, or market bid yields, to understand redemption value...

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What do I need to know about market yields, or market bid yields, to understand redemption value calculations in this subpart? 351.10 Section... Provisions § 351.10 What do I need to know about market yields, or market bid yields, to understand...

  15. 7 CFR 1942.9 - Planning, bidding, contracting, and constructing. [See §§ 1942.17(p) and 1942.18

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Planning, bidding, contracting, and constructing. [See...) ASSOCIATIONS Community Facility Loans § 1942.9 Planning, bidding, contracting, and constructing. [See §§ 1942....18(l) of this subpart will not be considered when an FmHA or its successor agency under Public Law...

  16. Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling.

    Science.gov (United States)

    Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

    2014-03-28

    12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation.

  17. Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling

    International Nuclear Information System (INIS)

    Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

    2014-01-01

    12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation

  18. Factores que influyen en la decisión de licitar o no licitar en la Franja de Gaza - perspectivas de los contratistas Factors affecting bid/no bid decision in the Gaza Strip -contractors' perspectives

    Directory of Open Access Journals (Sweden)

    Adnan Enshassi

    2011-01-01

    Full Text Available La decisión de licitar o no licitar un determinado proyecto es crucial para la sobrevivencia de los contratistas. El objetivo de este artículo es identificar y clasificar los factores que determinan la decisión de licitar o no licitar, de acuerdo a su importancia relativa desde la perspectiva de contratistas locales que operan en la Franja de Gaza, Palestina. Se identificaron un total de setenta y ocho factores, por medio de una revisión exhaustiva de la literatura, para evaluar los factores más importantes que afectan las decisiones de los contratistas por licitar no licitar en la Franja de Gaza. Se desarrolló una medición dentro de una muestra compuesta por setenta y tres contratistas clasificados bajo la categoría construcción, y sesenta y cinco de ellos respondieron a una razón de 89%. Los resultados ilustran que la reputación de los clientes, la capacidad financiera de éstos, el potencial financiero del proyecto y la disponibilidad constructiva de materias primas en los mercados locales, así como la estabilidad de la industria de la construcción, fueron los principales factores críticos que influyen en las decisiones de licitar o no licitar. Este estudio sugiere que los contratistas y clientes debieran mejorar sus sistemas financieros y aptitudes para poder mantenerse dentro del negocio.To bid or not to bid for a certain project is considered to be a crucial decision for contractors' survival. The objective of this paper is to identify and rank the factors that affect the bid/no bid decision according to their relative importance from the perspective of the local contractors operating in the Gaza Strip, Palestine. A total of seventy-eight factors were identified through a comprehensive literature review to evaluate the most important factors that affect the contractors' decisions to bid or not in the Gaza strip. A survey was conducted on a sample of seventy three contractors classified under the building category, and sixty

  19. 33 CFR 116.45 - Submission of bids, approval of award, guaranty of cost, and partial payments for bridges...

    Science.gov (United States)

    2010-07-01

    ... award, guaranty of cost, and partial payments for bridges eligible for funding under the Truman-Hobbs... SECURITY BRIDGES ALTERATION OF UNREASONABLY OBSTRUCTIVE BRIDGES § 116.45 Submission of bids, approval of award, guaranty of cost, and partial payments for bridges eligible for funding under the Truman-Hobbs...

  20. A Game Theoretical Approach Based Bidding Strategy Optimization for Power Producers in Power Markets with Renewable Electricity

    Directory of Open Access Journals (Sweden)

    Yi Tang

    2017-05-01

    Full Text Available In a competitive electricity market with substantial involvement of renewable electricity, maximizing profits by optimizing bidding strategies is crucial to different power producers including conventional power plants and renewable ones. This paper proposes a game-theoretic bidding optimization method based on bi-level programming, where power producers are at the upper level and utility companies are at the lower level. The competition among the multiple power producers is formulated as a non-cooperative game in which bidding curves are their strategies, while uniform clearing pricing is considered for utility companies represented by an independent system operator. Consequently, based on the formulated game model, the bidding strategies for power producers are optimized for the day-ahead market and the intraday market with considering the properties of renewable energy; and the clearing pricing for the utility companies, with respect to the power quantity from different power producers, is optimized simultaneously. Furthermore, a distributed algorithm is provided to search the solution of the generalized Nash equilibrium. Finally, simulation results were performed and discussed to verify the feasibility and effectiveness of the proposed non-cooperative game-based bi-level optimization approach.

  1. Requirement for aspartate-cleaved bid in apoptosis signaling by DNA-damaging anti-cancer regimens

    NARCIS (Netherlands)

    Werner, Arlette B.; Tait, Stephen W. G.; de Vries, Evert; Eldering, Eric; Borst, Jannie

    2004-01-01

    Lymphoid malignancies can escape from DNA-damaging anti-cancer drugs and gamma-radiation by blocking apoptosis-signaling pathways. How these regimens induce apoptosis is incompletely defined, especially in cells with nonfunctional p53. We report here that the BH3-only Bcl-2 family member Bid is

  2. 7 CFR 1726.253 - Prior approved contract modification related to alternative bid provision for payment to...

    Science.gov (United States)

    2010-01-01

    ... alternative bid provision for payment to contractor for bulk purchase of materials. 1726.253 Section 1726.253... contractor for bulk purchase of materials. When construction is to be performed over an extended period of... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Modifications to RUS Standard Contract Forms...

  3. A complex bid model and strategy for dispatchable loads in real-time market-based demand response

    NARCIS (Netherlands)

    Babar, M.; Nguyen, P.H.; Cuk, V.; Kamphuis, I.G.; Kling, W.L.

    2014-01-01

    The power system is moving into the new era of Smart Grid with the help of advance ICT and other developed technologies. These advancements made the demand response as an integral part of power and energy systems. Nowadays, the concept of Energy bidding is emerging in the Market-based Demand

  4. 76 FR 18578 - Notice of Realty Action: Competitive Sealed Bid Sale of Public Lands in Clark County, NV

    Science.gov (United States)

    2011-04-04

    ...; 11-08807; MO 4500019774; TAS: 14X5232] Notice of Realty Action: Competitive Sealed Bid Sale of Public... shall be accompanied by a cashier's check, certified check, or U.S. postal money order, and made payable... certified check, postal money order, bank draft or cashier's check made payable in U.S. dollars to the...

  5. 78 FR 25097 - Notice of Realty Action: Competitive, Sealed-Bid, Spring SNPLMA Sale of Public Lands in Clark...

    Science.gov (United States)

    2013-04-29

    ..., et al.; 13-08807; MO 4500049637; TAS: 14X5232] Notice of Realty Action: Competitive, Sealed-Bid... the sale must also include a certified check, postal money order, bank draft, or cashier's check made... in the form of a certified check, U.S. postal money order, bank draft, cashier's check, or made...

  6. 76 FR 56793 - Notice of Realty Action: Competitive, Sealed-Bid Sale of Public Lands in Clark County, NV

    Science.gov (United States)

    2011-09-14

    ...-89137; 11-08807; MO 4500022283; TAS: 14X5232] Notice of Realty Action: Competitive, Sealed-Bid Sale of... money order, bank draft, or cashier's check made payable in U.S. dollars to the ``Department of the... of a certified check, U.S. postal money order, bank draft, or cashier's check made payable in U.S...

  7. 77 FR 67021 - Notice of Realty Action: Competitive Sealed-Bid Sale of Public Land in Clark County, NV

    Science.gov (United States)

    2012-11-08

    ...; 12-08807; MO 4500036691; TAS: 14X5232] Notice of Realty Action: Competitive Sealed-Bid Sale of Public.... postal money order, bank draft, or cashier's check, and made payable in U.S. dollars to ``Department of... the form of a certified check, U.S. postal money order, bank draft or cashier's check made payable in...

  8. Bid-Induced Release of AIF/EndoG from Mitochondria Causes Apoptosis of Macrophages during Infection with Leptospira interrogans

    Directory of Open Access Journals (Sweden)

    Wei-Lin Hu

    2017-11-01

    Full Text Available Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF and endonuclease G (EndoG in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was not activated. Next, we found that the release and translocation of AIF and/or EndoG was preceded by the activation of the BH3-interacting domain death agonist (Bid. Furthermore, our data demonstrated that caspase-8 was activated during the infection and caused the activation of Bid. Meanwhile, high reactive oxygen species (ROS trigged by the infection caused the dephosphorylation of Akt, which also activated Bid. In conclusion, Bid-mediated mitochondrial release of AIF and/or EndoG followed by nuclear translocation is a major mechanism of leptospire- induced apoptosis in macrophages, and this process is modulated by both caspase-8 and ROS-Akt signal pathways.

  9. Bidding behavior when one bidder and the auctioneer are vertically integrated: implications for the partial deregulation of EU electricity markets

    Czech Academy of Sciences Publication Activity Database

    van Koten, Silvester

    -, č. 313 (2006), s. 1-35 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : asymmetric auctions * bidding behavior * electricity markets Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp313.pdf

  10. Evaluation of Orange and Rockland Utilities, Inc.`s competitive bidding program for demand-side resources. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Peters, J.S.; Stucky, L.; Seratt, P.; Darden-Butler, D. [Barakat and Chamberlin, Inc., Portland, OR (United States)

    1993-02-01

    The process evaluation reports on the implementation of Orange and Rockland Utilities demand-side bidding program in New York State during 1991 and 1992. The program is implemented by two energy service companies in Orange and rockland`s New York State service territory. The process evaluation methodology included interviews with utility staff (3), energy service company staff (2), and participating (6) and nonparticipating (7) utility customers. The two energy service companies had enrolled 14 customers in the program by summer 1992. One company had achieved 90% of their 2.75 MW bid and the other had achieved less than 90% of their 6.9 MW bid. Critical factors in success were determination of a reasonable bid amount for the market and marketing to the appropriate customers. Customers most interested in the program included those with limited access to capital and medium-sized firms with poor cash flows, particularly schools and hospitals. The findings also show that due to the incentive structure and associated need for substantial customer contributions, lighting measures dominate all installations. Customers, however, were interested in the potential savings and six of the nonparticipants chose to either install measures on their own or enroll in the utility`s rebate program.

  11. Influence of feasibility constrains on the bidding strategy selection in a day-ahead electricity market session

    International Nuclear Information System (INIS)

    Borghetti, Alberto; Massucco, Stefano; Silvestro, Federico

    2009-01-01

    Large part of liberalized electricity markets, including the Italian one, features an auction mechanism, called day-ahead energy market, which matches producers' and buyers' simple bids, consisting of energy quantity and price pairs. The match is achieved by a merit-order economic dispatch procedure independently applied for each of the hours of the following day. Power plants operation should, however, take into account several technical constraints, such as maximum and minimum production bounds, ramp constraints and minimum up and downs times, as well as no-load and startup costs. The presence of these constraints forces to adjust the scheduling provided by the market in order to obtain a feasible scheduling. The paper presents an analysis of the possibility and the limits of taking into account the power plants technical constraints in the bidding strategy selection procedure of generating companies (Gencos). The analysis is carried out by using a computer procedure based both on a simple static game-theory approach and on a cost-minimization unit-commitment algorithm. For illustrative purposes, we present the results obtained for a system with three Gencos, each owning several power plants, trying to model the bidding behaviour of every generator in the system. This approach, although complex from the computational point of view, allows an analysis of both price and quantity bidding strategies and appears to be applicable to markets having different rules and features. (author)

  12. The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook.

    Science.gov (United States)

    Stanger, Frédéric V; de Beer, Tjaart A P; Dranow, David M; Schirmer, Tilman; Phan, Isabelle; Dehio, Christoph

    2017-01-03

    The BID (Bep intracellular delivery) domain functions as secretion signal in a subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It mediates transfer of (1) relaxases and the attached DNA during bacterial conjugation, and (2) numerous Bartonella effector proteins (Beps) during protein transfer into host cells infected by pathogenic Bartonella species. Furthermore, BID domains of Beps have often evolved secondary effector functions within host cells. Here, we provide crystal structures for three representative BID domains and describe a novel conserved fold characterized by a compact, antiparallel four-helix bundle topped with a hook. The conserved hydrophobic core provides a rigid scaffold to a surface that, despite a few conserved exposed residues and similarities in charge distribution, displays significant variability. We propose that the genuine function of BID domains as T4S signal may primarily depend on their rigid structure, while the plasticity of their surface may facilitate adaptation to secondary effector functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 76 FR 16812 - Notice of Realty Action: Modified Competitive Bid Sale of Public Land in Santa Clara County, CA

    Science.gov (United States)

    2011-03-25

    ... County, California, for not less than the appraised fair market value of $41,000. The sale will be... fair market value of $41,000. Each sealed bid must include a certified check, money order, bank draft... concluded there are no known mineral values in the land proposed for sale. The proposed sale would include...

  14. A Sealed-Bid Two-Attribute Yardstick AuctionWithout Prior Scoring

    DEFF Research Database (Denmark)

    Leth Hougaard, Jens; Nielsen, Kurt; Papakonstantinou, Athanasios

    2016-01-01

    that following this type of equilibrium behavior often leads to winner’s curse. The simulations show that in auctions with more than 12 participants the chance of facing winner’s curse is around 95%. Truthful reporting, on the other hand, does not constitute a Nash equilibrium but it is ex post individually......We analyze a two-attribute single item procurement auction that uses yardstick competition to settle prices. The auction simplifies the procurement process by reducing the principal’s articulation of preferences to simply choosing the most preferred offer as if it was a market with posted prices...... rational. Using a simulation study we demonstrate that truthful bidding may indeed represent some kind of focal point....

  15. Support Vector Machines for decision support in electricity markets׳ strategic bidding

    DEFF Research Database (Denmark)

    Pinto, Tiago; Sousa, Tiago M.; Praça, Isabel

    2015-01-01

    . The ALBidS system allows MASCEM market negotiating players to take the best possible advantages from the market context. This paper presents the application of a Support Vector Machines (SVM) based approach to provide decision support to electricity market players. This strategy is tested and validated...... by being included in ALBidS and then compared with the application of an Artificial Neural Network (ANN), originating promising results: an effective electricity market price forecast in a fast execution time. The proposed approach is tested and validated using real electricity markets data from MIBEL......׳ research group has developed a multi-agent system: Multi-Agent System for Competitive Electricity Markets (MASCEM), which simulates the electricity markets environment. MASCEM is integrated with Adaptive Learning Strategic Bidding System (ALBidS) that works as a decision support system for market players...

  16. Neural correlates of reinforcement learning and social preferences in competitive bidding.

    Science.gov (United States)

    van den Bos, Wouter; Talwar, Arjun; McClure, Samuel M

    2013-01-30

    In competitive social environments, people often deviate from what rational choice theory prescribes, resulting in losses or suboptimal monetary gains. We investigate how competition affects learning and decision-making in a common value auction task. During the experiment, groups of five human participants were simultaneously scanned using MRI while playing the auction task. We first demonstrate that bidding is well characterized by reinforcement learning with biased reward representations dependent on social preferences. Indicative of reinforcement learning, we found that estimated trial-by-trial prediction errors correlated with activity in the striatum and ventromedial prefrontal cortex. Additionally, we found that individual differences in social preferences were related to activity in the temporal-parietal junction and anterior insula. Connectivity analyses suggest that monetary and social value signals are integrated in the ventromedial prefrontal cortex and striatum. Based on these results, we argue for a novel mechanistic account for the integration of reinforcement history and social preferences in competitive decision-making.

  17. Combined hydro-wind generation bids in a pool-based electricity market

    International Nuclear Information System (INIS)

    Angarita, Jorge L.; Usaola, Julio; Martinez-Crespo, Jorge

    2009-01-01

    Present regulatory trends are promoting the direct participation of wind energy in electricity markets. The final result of these markets sets the production scheduling for the operation time, including a power commitment from the wind generators. However, wind resources are uncertain, and the final power delivered usually differs from the initial power committed. This imbalance produces an overcost in the system, which must be paid by those who produce it, e.g., wind generators among others. As a result, wind farm revenue decreases, but it could increase by allowing wind farms to submit their bids to the markets together with a hydro generating unit, which may easily modify its production according to the expected imbalance. This paper presents a stochastic optimization technique that maximizes the joint profit of hydro and wind generators in a pool-based electricity market, taking into account the uncertainty of wind power prediction. (author)

  18. Bidding strategies for virtual power plants considering CHPs and intermittent renewables

    International Nuclear Information System (INIS)

    Zapata Riveros, J.; Bruninx, K.; Poncelet, K.; D’haeseleer, W.

    2015-01-01

    Highlights: • A stochastic optimization evaluates the optimal bidding strategy of a VPP. • Three different strategies were assessed: ‘static’, ‘flexible DA’ and ‘flexible RT’. • The ‘flexible RT’ attains the largest profits. It adapts the VPP output in real-time. - Abstract: Energy efficiency and renewable-energy sources (RES) are fundamental parts of the European energy policy. For this reason, efficient distributed generation technologies such as combined heat and power coupled to district heating (CHP–DH) and RES based electricity are largely promoted. Additionally, the flexibility that CHP–DH offers to the power system is seen as an option to balance the intermittent output of RES-based generation. This could be done by aggregating RES based electricity generation and CHP DH in a virtual power plant (VPP). In this framework, the present work presents a methodology to evaluate the optimal bidding strategy of a VPP composed of a CHP–DH and RES based generators. The objective is to investigate the optimal bidding strategy for a VPP that uses CHP DH to compensate for the uncertainties regarding RES-based electricity generation and market prices. The VPP operator nominates its energy to the day ahead market the day before the actual delivery (D-1). In real time, any deviation from the day-ahead schedule is settled in the imbalance market. The uncertainties are modeled using a two stage stochastic programming approach. Three different bidding strategies are studied: ‘static’, ‘flexible DA’ and ‘flexible RT’. The major difference between the studied strategies lies in the dispatch decisions. The ‘static’ strategy does not adjust the scheduled output of the CHP. Whereas, the ‘flexible DA’ and ‘flexible RT’ strategies differ from each other in terms of the information available at the moment of performing the reschedule (second stage decision). The ‘flexible DA’ reschedules the CHP output for the whole day assuming

  19. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID...

  20. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

    Science.gov (United States)

    Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M

    2015-01-01

    Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.