Nuclear Energy, Nuclear Weapons Proliferation, and the Arms Race.

ERIC Educational Resources Information Center

Hollander, Jack, Ed.

A symposium was organized to reexamine the realities of vertical proliferation between the United States and the Soviet Union and to place into perspective the horizontal proliferation of nuclear weapons throughout the world, including the possible role of commercial nuclear power in facilitating proliferation. The four invited symposium…

Worldwide Report, Nuclear Development and Proliferation

DTIC Science & Technology

1984-06-07

A 201204 JPRS-TND-84-013 7 June 1984 Worldwide Report NUCLEAR DEVELOPMENT AND PROLIFERATION \\ y0& ^ KK0 %>$JJMXSTT JWRTF-Tnuyy...Publications Research Service, 1000 North Glebe Road, Arlington, Virginia 22201. JPRS-TND-84-013 7 June 1984 WORLDWIDE REPORT NUCLEAR DEVELOPMENT AND...But China by no means favors nuclear proliferation by helping other countries to develop nuclear weapons, he declared. China holds, he said, that

78 FR 33995 - Nuclear Proliferation Assessment in Licensing Process for Enrichment or Reprocessing Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... designed to minimize proliferation risks world-wide, including the Nuclear Non- Proliferation Treaty, the U... and licensees ensure that they comply with requirements designed to minimize proliferation risks... NRC's regulations on physical security, information security, material control and accounting, cyber...

Leo Szilard Lectureship Award: Science Matters - Technical Dimensions of Arms Control and Non-Proliferation Agreements

NASA Astrophysics Data System (ADS)

Timbie, James

2017-01-01

Agreements to reduce nuclear arms and prevent proliferation of nuclear weapons are technical as well as political documents. They must be both technically sound and politically acceptable. This presentation illustrates technical aspects of arms control and non-proliferation agreements, with examples from SALT I, INF, the HEU Agreement, START, and the Iran nuclear negotiations, drawing on 44 years of personal experience in the negotiation of these agreements. The lecture is designed to convey an appreciation of the role that individuals with technical training can play in diplomatic efforts to reduce nuclear forces and prevent nuclear proliferation.

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

NASA Astrophysics Data System (ADS)

Kollar, Lenka

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

Economic and Non-proliferation Policy Considerations of Uranium Enrichment in Brazil and Argentina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Short, Steven M.; Phillips, Jon R.; Weimar, Mark R.

2008-09-01

The nuclear development programs of both Argentina and Brazil have, since the 1970s, been premised on the desire for self-sufficiency and assurance of nuclear fuel supply. While military rivalry and mutual distrust led to nuclear weapons related development programs in the 1970s and 1980s, both countries have since terminated these programs. Furthermore, the governments of both countries have pledged their commitment to exclusively non-explosive use of nuclear energy and have signed the Non Proliferation Treaty (NPT). Utilizing rights provided for under the NPT, both Argentina and Brazil have nuclear fuel production facilities, with the notable exception of enrichment plants, thatmore » provide much of the current indigenous fuel requirements for their nuclear power plants. However, both countries are actively developing enrichment capability to fill this gap. The purpose of this report is to assess the economic basis and non-proliferation policy considerations for indigenous enrichment capability within the context of their desired self-sufficiency and to evaluate possible United States Government policy options.« less

Proliferation of nuclear weapons: opportunities for control and abolition.

PubMed

Sidel, Victor W; Levy, Barry S

2007-09-01

Nuclear weapons pose a particularly destructive threat. Prevention of the proliferation and use of nuclear weapons is urgently important to public health. "Horizontal" proliferation refers to nation-states or nonstate entities that do not have, but are acquiring, nuclear weapons or developing the capability and materials for producing them. "Vertical" proliferation refers to nation-states that do possess nuclear weapons and are increasing their stockpiles of these weapons, improving the technical sophistication or reliability of their weapons, or developing new weapons. Because nation-states or other entities that wish to use or threaten to use nuclear weapons need methods for delivering those weapons, proliferation of delivery mechanisms must also be prevented. Controlling proliferation--and ultimately abolishing nuclear weapons--involves national governments, intergovernmental organizations, nongovernmental and professional organizations, and society at large.

The Non-Proliferation Treaty review: An American perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunn, L.A.

1985-01-01

Since the entry into the force in March 1970, the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) has played a central part in this decades-long endeavor. The Treaty's specific undertakings have been carefully crafted to serve its three major objectives. The first, which was the driving force behind the initial push for the NPT, is to prevent the further spread of nuclear weapons. The second is to foster peaceful nuclear cooperation under safeguards. The third objective, added during the multilateral negotiation of the NPT, is to encourage good faith negotiations to end the nuclear arms race with a viewmore » to general and complete disarmament.« less

Proliferation of Nuclear Weapons: Opportunities for Control and Abolition

PubMed Central

Sidel, Victor W.; Levy, Barry S.

2007-01-01

Nuclear weapons pose a particularly destructive threat. Prevention of the proliferation and use of nuclear weapons is urgently important to public health. “Horizontal” proliferation refers to nation-states or nonstate entities that do not have, but are acquiring, nuclear weapons or developing the capability and materials for producing them. “Vertical” proliferation refers to nation-states that do possess nuclear weapons and are increasing their stockpiles of these weapons, improving the technical sophistication or reliability of their weapons, or developing new weapons. Because nation-states or other entities that wish to use or threaten to use nuclear weapons need methods for delivering those weapons, proliferation of delivery mechanisms must also be prevented. Controlling proliferation—and ultimately abolishing nuclear weapons—involves national governments, intergovernmental organizations, nongovernmental and professional organizations, and society at large. PMID:17666690

Worldwide Report, Nuclear Development and Proliferation

DTIC Science & Technology

1984-07-02

delegate welcomed the inclusion of a new item-disarmament and development -on the commission’s agenda. Miss Kunadi said the catalytic effects of arms...249199 JPRS-TND-84-016 2 July 1984 — """ , f L ~ tibiae iel<M99; Worldwide Report NUCLEAR DEVELOPMENT AND PROLIFERATION mom m FBIS...Arlington, Virginia 22201. JPRS-TND-84- ■016 2 July 1984 WORLDWIDE REPORT NUCLEAR DEVELOPMENT AND PROLIFERATION CONTENTS ASIA PEOPLE ’S REPUBLIC OF

Stabilization and immobilization of military plutonium: A non-proliferation perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leventhal, P.

1996-05-01

The Nuclear Control Institute welcomes this DOE-sponsored technical workshop on stabilization and immobilization of weapons plutonium (W Pu) because of the significant contribution it can make toward the ultimate non-proliferation objective of eliminating weapons-usable nuclear material, plutonium and highly enriched uranium (HEU), from world commerce. The risk of theft or diversion of these materials warrants concern, as only a few kilograms in the hands of terrorists or threshold states would give them the capability to build nuclear weapons. Military plutonium disposition questions cannot be addressed in isolation from civilian plutonium issues. The National Academy of Sciences has urged that {open_quotes}furthermore » steps should be taken to reduce the proliferation risks posed by all of the world`s plutonium stocks, military and civilian, separated and unseparated...{close_quotes}. This report discusses vitrification and a mixed oxide fuels option, and the effects of disposition choices on civilian plutonium fuel cycles.« less

Geospatial Image Mining For Nuclear Proliferation Detection: Challenges and New Opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vatsavai, Raju; Bhaduri, Budhendra L; Cheriyadat, Anil M

2010-01-01

With increasing understanding and availability of nuclear technologies, and increasing persuasion of nuclear technologies by several new countries, it is increasingly becoming important to monitor the nuclear proliferation activities. There is a great need for developing technologies to automatically or semi-automatically detect nuclear proliferation activities using remote sensing. Images acquired from earth observation satellites is an important source of information in detecting proliferation activities. High-resolution remote sensing images are highly useful in verifying the correctness, as well as completeness of any nuclear program. DOE national laboratories are interested in detecting nuclear proliferation by developing advanced geospatial image mining algorithms. Inmore » this paper we describe the current understanding of geospatial image mining techniques and enumerate key gaps and identify future research needs in the context of nuclear proliferation.« less

The Power of Integrators, Financiers, and Insurers to Reduce Proliferation Risks: Nuclear Dual-Use Goods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weise, Rachel A.; Hund, Gretchen

2015-05-01

Globalization of manufacturing supply chains has changed the nature of nuclear proliferation. Before 1991, nonproliferation efforts focused almost exclusively on limiting the spread of materials and equipment specifically designed for nuclear use -- reactors, centrifuges, and fissile material. Dual-use items, those items with both nuclear and non-nuclear applications, were not closely scrutinized or controlled. However, in 1991 the international community discovered that Iraq had developed a fairly sophisticated nuclear weapons program by importing dual-use items; this discovery spurred the international community to increase controls on dual-use technologies. Despite these international efforts, dual-use items are still a challenge for those seekingmore » to limit proliferation.« less

Proliferation risks from nuclear power infrastructure

NASA Astrophysics Data System (ADS)

Squassoni, Sharon

2017-11-01

Certain elements of nuclear energy infrastructure are inherently dual-use, which makes the promotion of nuclear energy fraught with uncertainty. Are current restraints on the materials, equipment, and technology that can be used either to produce fuel for nuclear electricity generation or material for nuclear explosive devices adequate? Technology controls, supply side restrictions, and fuel market assurances have been used to dissuade countries from developing sensitive technologies but the lack of legal restrictions is a continued barrier to permanent reduction of nuclear proliferation risks.

The Gravest Danger:. Nuclear Weapons and Their Proliferation

NASA Astrophysics Data System (ADS)

Drell, S.

2005-02-01

Nuclear weapons are unique in their terrifying potential. With an energy release a million times larger than that of previous explosives, mass destruction is inevitable. The prospect of the spread of nuclear weapons and other dangerous technologies into the hands of suicidal terrorists and rogue nations unrestrained by the norms of civilized behavior has led President Bush to remark that "the gravest danger our nation faces lies at the crossroads of radicalism and technology." This talk will address what can and should be done, in the face of new challenges in times punctuated by terrorist threats, to sustain and strengthen the non-proliferation regime, taking into consideration technical realities, and the roles and limits of diplomatic initiatives and of military force.

Improved Technology To Prevent Nuclear Proliferation And Counter Nuclear Terrorism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, J; Yuldashev, B; Labov, S

2006-06-12

As the world moves into the 21st century, the possibility of greater reliance on nuclear energy will impose additional technical requirements to prevent proliferation. In addition to proliferation resistant reactors, a careful examination of the various possible fuel cycles from cradle to grave will provide additional technical and nonproliferation challenges in the areas of conversion, enrichment, transportation, recycling and waste disposal. Radiation detection technology and information management have a prominent role in any future global regime for nonproliferation. As nuclear energy and hence nuclear materials become an increasingly global phenomenon, using local technologies and capabilities facilitate incorporation of enhanced monitoringmore » and detection on the regional level. Radiation detection technologies are an important tool in the prevention of proliferation and countering radiological/nuclear terrorism. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, passive detection, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. For example, various gamma ray imaging approaches are being explored to combine spatial resolution with background suppression in order to enhance sensitivity many-fold at reasonable standoff distances and acquisition times. New materials and approaches are being developed in order to provide adequate energy resolution in field use without the necessity for liquid nitrogen. Different detection algorithms enable fissile materials to be distinguished from other radioisotopes.« less

Proliferation resistance assessments during the design phase of a recycling facility as a means of reducing proliferation risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindell, M.A.; Grape, S.; Haekansson, A.

The sustainability criterion for Gen IV nuclear energy systems inherently presumes the availability of efficient fuel recycling capabilities. One area for research on advanced fuel recycling concerns safeguards aspects of this type of facilities. Since a recycling facility may be considered as sensitive from a non-proliferation perspective, it is important to address these issues early in the design process, according to the principle of Safeguards By Design. Presented in this paper is a mode of procedure, where assessments of the proliferation resistance (PR) of a recycling facility for fast reactor fuel have been performed so as to identify the weakestmore » barriers to proliferation of nuclear material. Two supplementing established methodologies have been applied; TOPS (Technological Opportunities to increase Proliferation resistance of nuclear power Systems) and PR-PP (Proliferation Resistance and Physical Protection evaluation methodology). The chosen fuel recycling facility belongs to a small Gen IV lead-cooled fast reactor system that is under study in Sweden. A schematic design of the recycling facility, where actinides are separated using solvent extraction, has been examined. The PR assessment methodologies make it possible to pinpoint areas in which the facility can be improved in order to reduce the risk of diversion. The initial facility design may then be slightly modified and/or safeguards measures may be introduced to reduce the total identified proliferation risk. After each modification of design and/or safeguards implementation, a new PR assessment of the revised system can then be carried out. This way, each modification can be evaluated and new ways to further enhance the proliferation resistance can be identified. This type of iterative procedure may support Safeguards By Design in the planning of new recycling plants and other nuclear facilities. (authors)« less

41 CFR 109-45.309-53 - Nuclear-related or proliferation sensitive property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Nuclear-related or proliferation sensitive property. 109-45.309-53 Section 109-45.309-53 Public Contracts and Property Management... Personal Property § 109-45.309-53 Nuclear-related or proliferation sensitive property. Nuclear-related or...

41 CFR 109-45.309-53 - Nuclear-related or proliferation sensitive property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Nuclear-related or proliferation sensitive property. 109-45.309-53 Section 109-45.309-53 Public Contracts and Property Management... Personal Property § 109-45.309-53 Nuclear-related or proliferation sensitive property. Nuclear-related or...

41 CFR 109-45.309-53 - Nuclear-related or proliferation sensitive property.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Nuclear-related or proliferation sensitive property. 109-45.309-53 Section 109-45.309-53 Public Contracts and Property Management... Personal Property § 109-45.309-53 Nuclear-related or proliferation sensitive property. Nuclear-related or...

41 CFR 109-45.309-53 - Nuclear-related or proliferation sensitive property.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Nuclear-related or proliferation sensitive property. 109-45.309-53 Section 109-45.309-53 Public Contracts and Property Management... Personal Property § 109-45.309-53 Nuclear-related or proliferation sensitive property. Nuclear-related or...

41 CFR 109-45.309-53 - Nuclear-related or proliferation sensitive property.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Nuclear-related or proliferation sensitive property. 109-45.309-53 Section 109-45.309-53 Public Contracts and Property Management... Personal Property § 109-45.309-53 Nuclear-related or proliferation sensitive property. Nuclear-related or...

Proliferating cell nuclear antigen promotes cell proliferation and tumorigenesis by up-regulating STAT3 in non-small cell lung cancer.

PubMed

Wang, Liuxin; Kong, Weixiang; Liu, Bing; Zhang, Xueqing

2018-08-01

Proliferating cell nuclear antigen (PCNA) functions as a bridging molecule, which targets proteins that have distinct roles in cell growth. The expression of PCNA is dysregulated in some tumors and takes part in the progression of oncogenesis. However, the roles of PCNA in the progression of non-small cell lung cancer (NSCLC) remain unknown. The present study aimed to investigate the function of PCNA in the occurrence and development of NSCLC and its underlying molecular mechanisms. Western blotting, RT-PCR, and immunohistochemistry assays were used to detect the expression pattern of PCNA in NSCLC tissues and cells. A log rank test was performed to compare the overall survival (OS) of patients with high/low expression of PCNA. Besides, the relationship between PCNA and signal transducer and activator of transcription-3 (STAT3) proteins were evaluated. Then, MTT, flow cytometry, clonal formation, and in vivo xenograft assays were conducted to investigate the effects of PCNA/STAT3 on cell growth, clonal formation, apoptosis, and tumorigenesis. Results showed that PCNA expression was elevated in NSCLC tissues and cells and it could combine with STAT3 and increased its expression and phosphorylation. Moreover, the expression of PCNA showed a positive correlation with the TNM grade and occurrence rate of the lymphatic metastasis and poor prognosis of NSCLC patients. Overexpression of PCNA promoted cell proliferation, clonal formation, and tumorigenesis in lung cancer cells and inhibited cell apoptosis. In contrast, these effects were inhibited when knockdown of STAT3. In conclusion, this study demonstrates that PCNA functions as an oncogene in the progression of NSCLC through up-regulation of STAT3. These findings point to a potentially new therapeutic strategy for NSCLC. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia.

PubMed

Ohayon, Delphine; De Chiara, Alessia; Chapuis, Nicolas; Candalh, Céline; Mocek, Julie; Ribeil, Jean-Antoine; Haddaoui, Lamya; Ifrah, Norbert; Hermine, Olivier; Bouillaud, Frédéric; Frachet, Philippe; Bouscary, Didier; Witko-Sarsat, Véronique

2016-10-19

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux.

Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia

PubMed Central

Ohayon, Delphine; De Chiara, Alessia; Chapuis, Nicolas; Candalh, Céline; Mocek, Julie; Ribeil, Jean-Antoine; Haddaoui, Lamya; Ifrah, Norbert; Hermine, Olivier; Bouillaud, Frédéric; Frachet, Philippe; Bouscary, Didier; Witko-Sarsat, Véronique

2016-01-01

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux. PMID:27759041

41 CFR 109-43.305-50 - Nuclear-related and proliferation-sensitive personal property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Nuclear-related and proliferation-sensitive personal property. 109-43.305-50 Section 109-43.305-50 Public Contracts and Property... Excess § 109-43.305-50 Nuclear-related and proliferation-sensitive personal property. Nuclear-related and...

41 CFR 109-43.305-50 - Nuclear-related and proliferation-sensitive personal property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Nuclear-related and proliferation-sensitive personal property. 109-43.305-50 Section 109-43.305-50 Public Contracts and Property... Excess § 109-43.305-50 Nuclear-related and proliferation-sensitive personal property. Nuclear-related and...

41 CFR 109-43.305-50 - Nuclear-related and proliferation-sensitive personal property.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Nuclear-related and proliferation-sensitive personal property. 109-43.305-50 Section 109-43.305-50 Public Contracts and Property... Excess § 109-43.305-50 Nuclear-related and proliferation-sensitive personal property. Nuclear-related and...

41 CFR 109-43.305-50 - Nuclear-related and proliferation-sensitive personal property.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Nuclear-related and proliferation-sensitive personal property. 109-43.305-50 Section 109-43.305-50 Public Contracts and Property... Excess § 109-43.305-50 Nuclear-related and proliferation-sensitive personal property. Nuclear-related and...

41 CFR 109-43.305-50 - Nuclear-related and proliferation-sensitive personal property.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Nuclear-related and proliferation-sensitive personal property. 109-43.305-50 Section 109-43.305-50 Public Contracts and Property... Excess § 109-43.305-50 Nuclear-related and proliferation-sensitive personal property. Nuclear-related and...

[The Chinese nuclear test and 'atoms for peace' as a measure for preventing nuclear armament of Japan: the nuclear non-proliferation policy of the United States and the introduction of light water reactors into Japan, 1964-1968].

PubMed

Yamazaki, Masakatsu

2014-07-01

Japan and the United States signed in 1968 a new atomic energy agreement through which US light-water nuclear reactors, including those of the Fukushima Daiichi Nuclear Power Plant of Tokyo Electric Power Company, were to be introduced into Japan. This paper studies the history of negotiations for the 1968 agreement using documents declassified in the 1990s in the US and Japan. After the success of the Chinese nuclear test in October 1964, the United States became seriously concerned about nuclear armament of other countries in Asia including Japan. Expecting that Japan would not have its own nuclear weapons, the US offered to help the country to demonstrate its superiority in some fields of science including peaceful nuclear energy to counter the psychological effect of the Chinese nuclear armament. Driven by his own political agenda, the newly appointed Prime Minister Eisaku Sato responded to the US expectation favorably. When he met in January 1965 with President Johnson, Sato made it clear that Japan would not pursue nuclear weapons. Although the US continued its support after this visit, it nevertheless gave priority to the control of nuclear technology in Japan through the bilateral peaceful nuclear agreement. This paper argues that the 1968 agreement implicitly meant a strategic measure to prevent Japan from going nuclear and also a tactic to persuade Japan to join the Nuclear Non -Proliferation Treaty.

Assessing State Nuclear Weapons Proliferation: Using Bayesian Network Analysis of Social Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coles, Garill A.; Brothers, Alan J.; Olson, Jarrod

A Bayesian network (BN) model of social factors can support proliferation assessments by estimating the likelihood that a state will pursue a nuclear weapon. Social factors including political, economic, nuclear capability, security, and national identity and psychology factors may play as important a role in whether a State pursues nuclear weapons as more physical factors. This paper will show how using Bayesian reasoning on a generic case of a would-be proliferator State can be used to combine evidence that supports proliferation assessment. Theories and analysis by political scientists can be leveraged in a quantitative and transparent way to indicate proliferationmore » risk. BN models facilitate diagnosis and inference in a probabilistic environment by using a network of nodes and acyclic directed arcs between the nodes whose connections, or absence of, indicate probabilistic relevance, or independence. We propose a BN model that would use information from both traditional safeguards and the strengthened safeguards associated with the Additional Protocol to indicate countries with a high risk of proliferating nuclear weapons. This model could be used in a variety of applications such a prioritization tool and as a component of state safeguards evaluations. This paper will discuss the benefits of BN reasoning, the development of Pacific Northwest National Laboratory’s (PNNL) BN state proliferation model and how it could be employed as an analytical tool.« less

US arms control obligations under the Non-Proliferation Treaty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-06-27

Article VI of the 1968 Non-Proliferation Treaty (NPT) obligates the nuclear weapon states parties to the Treaty ''to pursue negotiations in good faith on effective measures relating to cessation of the nuclear arms race, ... to nuclear disarmament, and on a treaty on general and complete disarmament under strict and effective international control.'' The preamble to the NPT recalls the 1963 Limited Test Ban Treaty ''determination ... to achieve the discontinuance of ... explosions.'' These provisions are interpreted by a majority of the non-nuclear weapon states parties to the Treaty as an obligation of the nuclear weapon states parties tomore » the Treaty to pursue a comprehensive test ban (CTB). However, a review of the history of the NPT negotiations and US ratification proceedings makes clear that the NPT imposes no legal obligation on the US to pursue a CTB. The US did not make a one-to-one correspondence between Article VI and any specific arms control measure; to the contrary, the US argued successfully that such a connection (to any specific measure) would be pernicious to the attempt to achieve agreement on the NPT. This interpretation, which was sustained through the negotiations and the ratification proceedings, still reflects the limits of the legal obligations the US has accepted. But, in the absence of progress on other arms control measures, which would relieve the pressure for a CTB, the majority interpretation creates political difficulties for the US and could threaten the NPT regime in the future. These problems highlight the need for the US to better defend its compliance with Article VI and to develop a long-term strategy that will permit necessary testing while assuring the survival of the NPT regime in effective form.« less

Commercial Satellite Imagery Analysis for Countering Nuclear Proliferation

NASA Astrophysics Data System (ADS)

Albright, David; Burkhard, Sarah; Lach, Allison

2018-05-01

High-resolution commercial satellite imagery from a growing number of private satellite companies allows nongovernmental analysts to better understand secret or opaque nuclear programs of countries in unstable or tense regions, called proliferant states. They include North Korea, Iran, India, Pakistan, and Israel. By using imagery to make these countries’ aims and capabilities more transparent, nongovernmental groups like the Institute for Science and International Security have affected the policies of governments and the course of public debate. Satellite imagery work has also strengthened the efforts of the International Atomic Energy Agency, thereby helping this key international agency build its case to mount inspections of suspect sites and activities. This work has improved assessments of the nuclear capabilities of proliferant states. Several case studies provide insight into the use of commercial satellite imagery as a key tool to educate policy makers and affect policy.

Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation.

PubMed Central

Kubben, F J; Peeters-Haesevoets, A; Engels, L G; Baeten, C G; Schutte, B; Arends, J W; Stockbrügger, R W; Blijham, G H

1994-01-01

Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with BrdU. There was, however, a good correlation between the results from both techniques (r = 0.6275; p < 0.05). Decrease in proliferation index along the colorectum was seen with both staining methods but was clearer with PCNA immunohistochemistry (caecum/ascending colon v rectum: 12.0 v 7.2; p < 0.004). The total number of crypt cells also decreased from proximal to distal (134 to 128; p < 0.06) but at no site correlated significantly with the proliferation index. It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay. Images Figure 4 PMID:7909785

Long-term proliferation and safeguards issues in future technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keisch, B.; Auerbach, C.; Fainberg, A.

1986-02-01

The purpose of the task was to assess the effect of potential new technologies, nuclear and non-nuclear, on safeguards needs and non-proliferation policies, and to explore possible solutions to some of the problems envisaged. Eight subdivisions were considered: New Enrichment Technologies; Non-Aqueous Reprocessing Technologies; Fusion; Accelerator-Driven Reactor Systems; New Reactor Types; Heavy Water and Deuterium; Long-Term Storage of Spent Fuel; and Other Future Technologies (Non-Nuclear). For each of these subdivisions, a careful review of the current world-wide effort in the field provided a means of subjectively estimating the viability and qualitative probability of fruition of promising technologies. Technologies for whichmore » safeguards and non-proliferation requirements have been thoroughly considered by others were not restudied here (e.g., the Fast Breeder Reactor). The time scale considered was 5 to 40 years for possible initial demonstration although, in some cases, a somewhat optimistic viewpoint was embraced. Conventional nuclear-material safeguards are only part of the overall non-proliferation regime. Other aspects are international agreements, export controls on sensitive technologies, classification of information, intelligence gathering, and diplomatic initiatives. The focus here is on safeguards, export controls, and classification.« less

Management and non-supervisory perceptions surrounding the implementation and significance of high-performance work practices in a nuclear power plant

NASA Astrophysics Data System (ADS)

Ashbridge, Gayle Ann

Change management has become an imperative for organizations as they move into the 21st century; up to 75 percent of change initiatives fail. Nuclear power plants face the same challenges as industrial firms with the added challenge of deregulation. Faced with this challenge, restructuring the electric utility has raised a number of complex issues. Under traditional cost-of-service regulation, electric utilities were able to pass on their costs to consumers who absorbed them. In the new competitive environment, customers will now choose their suppliers based on the most competitive price. The purpose of this study is to determine the degree of congruence between non-supervisory and supervisory personnel regarding the perceived implementation of high performance workplace practices at a nuclear power plant. This study used as its foundation the practices identified in the Road to High Performance Workplaces: A Guide to Better Jobs and Better Business Results by the U.S. Department of Labor's Office of the American Workplace (1994). The population for this study consisted of organizational members at one nuclear power plant. Over 300 individuals completed surveys on high performance workplace practices. Two surveys were administered, one to non-supervisory personnel and one to first line supervisors and above. The determination of implementation levels was accomplished through descriptive statistical analysis. Results of the study revealed 32 areas of noncongruence between non-supervisory and supervisory personnel in regard to the perceived implementation level of the high performance workplace practices. Factor analysis further revealed that the order in which the respondents place emphasis on the variables varies between the two groups. This study provides recommendations that may improve the nuclear power plants alignment of activities. Recommendations are also provided for additional research on high-performance work practices.

Supervised Semantic Classification for Nuclear Proliferation Monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2010-01-01

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

A Non-Proliferating Fuel Cycle: No Enrichment, Reprocessing or Accessible Spent Fuel - 12375

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, Frank L.

2012-07-01

Current fuel cycles offer a number of opportunities for access to plutonium, opportunities to create highly enriched uranium and access highly radioactive wastes to create nuclear weapons and 'dirty' bombs. The non-proliferating fuel cycle however eliminates or reduces such opportunities and access by eliminating the mining, milling and enrichment of uranium. The non-proliferating fuel cycle also reduces the production of plutonium per unit of energy created, eliminates reprocessing and the separation of plutonium from the spent fuel and the creation of a stream of high-level waste. It further simplifies the search for land based deep geologic repositories and interim storagemore » sites for spent fuel in the USA by disposing of the spent fuel in deep sub-seabed sediments after storing the spent fuel at U.S. Navy Nuclear Shipyards that have the space and all of the necessary equipment and security already in place. The non-proliferating fuel cycle also reduces transportation risks by utilizing barges for the collection of spent fuel and transport to the Navy shipyards and specially designed ships to take the spent fuel to designated disposal sites at sea and to dispose of them there in deep sub-seabed sediments. Disposal in the sub-seabed sediments practically eliminates human intrusion. Potential disposal sites include Great Meteor East and Southern Nares Abyssal Plain. Such sites then could easily become international disposal sites since they occur in the open ocean. It also reduces the level of human exposure in case of failure because of the large physical and chemical dilution and the elimination of a major pathway to man-seawater is not potable. Of course, the recovery of uranium from sea water and the disposal of spent fuel in sub-seabed sediments must be proven on an industrial scale. All other technologies are already operating on an industrial scale. If externalities, such as reduced terrorist threats, environmental damage (including embedded emissions

Nuclear Forensics: A Methodology Applicable to Nuclear Security and to Non-Proliferation

NASA Astrophysics Data System (ADS)

Mayer, K.; Wallenius, M.; Lützenkirchen, K.; Galy, J.; Varga, Z.; Erdmann, N.; Buda, R.; Kratz, J.-V.; Trautmann, N.; Fifield, K.

2011-09-01

Nuclear Security aims at the prevention and detection of and response to, theft, sabotage, unauthorized access, illegal transfer or other malicious acts involving nuclear material. Nuclear Forensics is a key element of nuclear security. Nuclear Forensics is defined as a methodology that aims at re-establishing the history of nuclear material of unknown origin. It is based on indicators that arise from known relationships between material characteristics and process history. Thus, nuclear forensics analysis includes the characterization of the material and correlation with production history. To this end, we can make use of parameters such as the isotopic composition of the nuclear material and accompanying elements, chemical impurities, macroscopic appearance and microstructure of the material. In the present paper, we discuss the opportunities for attribution of nuclear material offered by nuclear forensics as well as its limitations. Particular attention will be given to the role of nuclear reactions. Such reactions include the radioactive decay of the nuclear material, but also reactions with neutrons. When uranium (of natural composition) is exposed to neutrons, plutonium is formed, as well as 236U. We will illustrate the methodology using the example of a piece of uranium metal that dates back to the German nuclear program in the 1940's. A combination of different analytical techniques and model calculations enables a nuclear forensics interpretation, thus correlating the material characteristics with the production history.

Combating the Proliferation of Weapons of Mass Destruction.

ERIC Educational Resources Information Center

Jenkins, Bonnie

1997-01-01

Reveals the growing threat posed to all countries by the proliferation of weapons of mass destruction. Discusses the international effort combating this proliferation including the Nuclear Non-Proliferation Treaty, Strategic Arms Reduction Treaties, Biological Weapons Convention, and Chemical Weapons Convention. Also considers regional arms…

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina.

PubMed

Klimovich, Alexander; Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo; Bosch, Thomas C G

2018-05-10

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra , the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra . A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans.

Karyopherin alpha 1 regulates satellite cell proliferation and survival by modulating nuclear import

PubMed Central

Choo, Hyo-Jung; Cutler, Alicia; Rother, Franziska; Bader, Michael; Pavlath, Grace K.

2016-01-01

Satellite cells are stem cells with an essential role in skeletal muscle repair. Precise regulation of gene expression is critical for proper satellite cell quiescence, proliferation, differentiation and self -renewal. Nuclear proteins required for gene expression are dependent on the nucleocytoplasmic transport machinery to access to nucleus, however little is known about regulation of nuclear transport in satellite cells. The best characterized nuclear import pathway is classical nuclear import which depends on a classical nuclear localization signal (cNLS) in a cargo protein and the heterodimeric import receptors, karyopherin alpha (KPNA) and beta (KPNB). Multiple KPNA1 paralogs exist and can differ in importing specific cNLS proteins required for cell differentiation and function. We show that transcripts for six Kpna paralogs underwent distinct changes in mouse satellite cells during muscle regeneration accompanied by changes in cNLS proteins in nuclei. Depletion of KPNA1, the most dramatically altered KPNA, caused satellite cells in uninjured muscle to prematurely activate, proliferate and undergo apoptosis leading to satellite cell exhaustion with age. Increased proliferation of satellite cells led to enhanced muscle regeneration at early stages of regeneration. In addition, we observed impaired nuclear localization of two key KPNA1 cargo proteins: p27, a cyclin-dependent kinase inhibitor associated with cell cycle control and lymphoid enhancer factor 1, a critical co-transcription factor for β-catenin. These results indicate that regulated nuclear import of proteins by KPNA1 is critical for satellite cell proliferation and survival and establish classical nuclear import as a novel regulatory mechanism for controlling satellite cell fate. PMID:27434733

Nuclear Symbolism and Ritual--Upholding the National Myth: A Study of Indian and Pakistani Nuclear Proliferation

DTIC Science & Technology

2017-06-01

be abolished as a means of settling any problem. Indian President Rajendra Prasad, February 21, 1955 We have a big bomb now Indian Prime...Nuclear Bomb : The Impact on Global Proliferation, Updated ed (Berkeley London: University of California Press, 1999). 33. 4 Perkovich, India’s Nuclear... Bomb . 292. 5 Perkovich, India’s Nuclear Bomb . 409. 6 Perkovich, India’s Nuclear Bomb . 6. 4 weapons were considered rogue. Thus, India’s refusal

United States' arms control obligations under the NonProliferation Treaty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-06-27

Article VI of the 1986 Non-Proliferation Treaty obligates the nuclear weapon states party to the Treaty ''to pursue negotiations in good faith on effective measures relating to cessation of the nuclear arms race, ...to nuclear disarmament, and on a treaty on general and complete disarmament under strict and effective international control.'' The preamble to the NPT refers to the 1963 Limited Test Ban Treaty ''determination...to achieve the discontinuance of...explosions.'' These provisions are interpreted by many non-nuclear weapon states party to the NPT as an obligation of the nuclear weapon states party to the treaty to pursue a comprehensive test banmore » (CTB). However, a review of the history of the NPT negotiations and US ratification proceedings makes clear that Article VI imposes no legal obligation on the US to pursue a CTB. The United States did not make a one-to-one correspondence between Article VI and any specific arms control measure; to the contrary, the United States argued successfully that such a connection (to any specific measure) would be pernicious to the attempt to achieve agreement on the NPT. This interpretation held through the negotiations and ratification proceedings. However, a majority of NPT signatories assert that Article VI does indeed imply a commitment to a CTB. In the absence of progress on other arms control measures, which would relieve the pressure for a CTB, this interpretation creates a political problem for the US and could threaten the NPT regime in the future. These problems emphasize the need for the United States to more clearly explain its compliance with Article VI and to develop a long-term strategy that will permit necessary testing while assuring the survival of the NPT regime in effective form.« less

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina

PubMed Central

Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo

2018-01-01

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra. We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra, the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra. A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans. PMID:29754147

The myth of the ``proliferation-resistant'' closed nuclear fuel cycle

NASA Astrophysics Data System (ADS)

Lyman, Edwin S.

2000-07-01

National nuclear energy programs that engage in reprocessing of spent nuclear fuel (SNF) and the development of "closed" nuclear fuel cycles based on the utilization of plutonium process and store large quantities of weapons-usable nuclear materials in forms vulnerable to diversion or theft by national or subnational groups. Proliferation resistance, an idea dating back at least as far as the International Fuel Cycle Evaluation (INFCE) of the late 1970s, is a loosely defined term referring to processes for chemical separation of SNF that do not extract weapons-usable materials in a purified form.

75 FR 34919 - Continuation of the National Emergency With Respect To the Risk of Nuclear Proliferation Created...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... To the Risk of Nuclear Proliferation Created By the Accumulation of Weapons-usable Fissile Material... Risk of Nuclear Proliferation Created By the Accumulation of Weapons-usable Fissile Material In the... Russian Federation Concerning the Disposition of Highly Enriched Uranium Extracted from Nuclear Weapons...

On the future of civilian plutonium: An assessment of technological impediments to nuclear terrorism and proliferation

NASA Astrophysics Data System (ADS)

Avedon, Roger Edmond

This dissertation addresses the value of developing diversion- and theft-resistant nuclear power technology, given uncertain future demand for nuclear power, and uncertain risks of nuclear terrorism and of proliferation from the reprocessing of civilian plutonium. The methodology comprises four elements: Economics. An economic growth model coupled with market penetration effects for plutonium and for the hypothetical new technology provides a range of estimates for future nuclear demand. A flow model accounts for the longevity of capital assets (nuclear plants) over time. Terrorism. The commercial nuclear fuel cycle may provide a source of fissile material for terrorists seeking to construct a crude nuclear device. An option value model is used to estimate the effects of the hypothetical new technology on reducing the probability of theft. A game theoretic model is used to explore the deterrence value of physical security and then to draw conclusions about how learning on the part of terrorists or security forces might affect the theft estimate. The principal uncertainties in the theft model can be updated using Bayesian techniques as new data emerge. Proliferation. Access to fissile material is the principal technical impediment to a state's acquisition of nuclear weapons. A game theoretic model is used to determine the circumstances under which a state may proliferate via diversion. The model shows that the hypothetical new technology will have little value for counter-proliferation if diversion is not a preferred proliferation method. A technology policy analysis of the choice of proliferation method establishes that diversion is unlikely to be used because it has no constituency among the important parties to the decision, namely the political leadership, the scientific establishment, and the military. Value. The decision whether to develop a diversion- and theft-resistant fuel cycle depends on the perceived value of avoiding nuclear terrorism and proliferation

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Nuclear-related or... Excess § 109-43.307-52 Nuclear-related or proliferation-sensitive personal property. (a) Recognizing that property disposal officials will not have the technical knowledge to identify nuclear-related and...

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Nuclear-related or... Excess § 109-43.307-52 Nuclear-related or proliferation-sensitive personal property. (a) Recognizing that property disposal officials will not have the technical knowledge to identify nuclear-related and...

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Nuclear-related or... Excess § 109-43.307-52 Nuclear-related or proliferation-sensitive personal property. (a) Recognizing that property disposal officials will not have the technical knowledge to identify nuclear-related and...

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Nuclear-related or... Excess § 109-43.307-52 Nuclear-related or proliferation-sensitive personal property. (a) Recognizing that property disposal officials will not have the technical knowledge to identify nuclear-related and...

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Nuclear-related or... Excess § 109-43.307-52 Nuclear-related or proliferation-sensitive personal property. (a) Recognizing that property disposal officials will not have the technical knowledge to identify nuclear-related and...

3 CFR - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Code of Federal Regulations, 2013 CFR

2013-01-01

... to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons-Usable Fissile Material... Proliferation Created by the Accumulation of Weapons-Usable Fissile Material in the Territory of the Russian... Disposition of Highly Enriched Uranium Extracted from Nuclear Weapons, dated February 18, 1993, and related...

3 CFR - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Code of Federal Regulations, 2011 CFR

2011-01-01

... to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons-usable Fissile Material... Proliferation Created by the Accumulation of Weapons-usable Fissile Material in the Territory of the Russian... Disposition of Highly Enriched Uranium Extracted from Nuclear Weapons, dated February 18, 1993, and related...

Sensor Fusion for Nuclear Proliferation Activity Monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adel Ghanem, Ph D

2007-03-30

The objective of Phase 1 of this STTR project is to demonstrate a Proof-of-Concept (PoC) of the Geo-Rad system that integrates a location-aware SmartTag (made by ZonTrak) and a radiation detector (developed by LLNL). It also includes the ability to transmit the collected radiation data and location information to the ZonTrak server (ZonService). The collected data is further transmitted to a central server at LLNL (the Fusion Server) to be processed in conjunction with overhead imagery to generate location estimates of nuclear proliferation and radiation sources.

Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna

2013-02-01

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies includingmore » Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.« less

Method of increasing the deterrent to proliferation of nuclear fuels

DOEpatents

Rampolla, Donald S.

1982-01-01

A process of recycling protactinium-231 to enhance the utilization of radioactively hot uranium-232 in nuclear fuel for the purpose of making both fresh and spent fuel more resistant to proliferation. The uranium-232 may be obtained by the irradiation of protactinium-231 which is normally found in the spent fuel rods of a thorium base nuclear reactor. The production of protactinium-231 and uranium-232 would be made possible by the use of the thorium uranium-233 fuel cycle in power reactors.

Role of YAP activation in nuclear receptor CAR-mediated proliferation of mouse hepatocytes.

PubMed

Abe, Taiki; Amaike, Yuto; Shizu, Ryota; Takahashi, Miki; Kano, Makoto; Hosaka, Takuomi; Sasaki, Takamitsu; Kodama, Susumu; Matsuzawa, Atsushi; Yoshinari, Kouichi

2018-06-08

Constitutive androstane receptor (CAR) is a xenobiotic-responsive nuclear receptor that is highly expressed in the liver. CAR activation induces hepatocyte proliferation and hepatocarcinogenesis in rodents, but the mechanisms remain unclear. In this study, we investigated the association of CAR-dependent cell proliferation with Yes-associated protein (YAP), which is a transcriptional cofactor controlling organ size and cell growth through the interaction with various transcriptional factors including TEAD. In mouse livers, TCPOBOP (a mouse CAR activator) treatment increased the nuclear YAP accumulation and mRNA levels of YAP target genes as well as cell-cycle related genes along with liver hypertrophy and verteporfin (an inhibitor of YAP/TEAD interaction) cotreatment tended to attenuate them. Furthermore, in cell-based reporter gene assays, CAR activation enhanced the YAP/TEAD-dependent transcription. To investigate the role of YAP/TEAD activation in the CAR-dependent hepatocyte proliferation, we sought to establish an in vitro system completely reproducing CAR-dependent cell proliferation. Since CAR was only slightly expressed in cultured mouse primary hepatocytes compared to mouse livers and no proliferation was observed after treatment with TCPOBOP, we overexpressed CAR using mouse CAR expressing adenovirus (Ad-mCAR-V5) in mouse primary hepatocytes. Ad-mCAR-V5 infection and TCPOBOP treatment induced hepatocyte proliferation. Similar results were obtained with immortalized normal mouse hepatocytes as well. In the established in vitro system, CAR-dependent proliferation was strongly inhibited by Yap knockdown and completely abolished by verteporfin treatment. Our present results obtained in in vivo and in vitro experiments suggest that YAP/TEAD activation plays key roles in CAR-dependent proliferation of murine hepatocytes.

The Nuclear Power and Nuclear Weapons Connection.

ERIC Educational Resources Information Center

Leventhal, Paul

1990-01-01

Explains problems enforcing the Nuclear Non-Proliferation Treaty (NPT) of 1968. Provides factual charts and details concerning the production of nuclear energy and arms, the processing and disposal of waste products, and outlines the nuclear fuel cycle. Discusses safeguards, the risk of nuclear terrorism, and ways to deal with these problems. (NL)

Non-woven PGA/PVA fibrous mesh as an appropriate scaffold for chondrocyte proliferation.

PubMed

Rampichová, M; Koštáková, E; Filová, E; Prosecká, E; Plencner, M; Ocheretná, L; Lytvynets, A; Lukáš, D; Amler, E

2010-01-01

Non-woven textile mesh from polyglycolic acid (PGA) was found as a proper material for chondrocyte adhesion but worse for their proliferation. Neither hyaluronic acid nor chitosan nor polyvinyl alcohol (PVA) increased chondrocyte adhesion. However, chondrocyte proliferation suffered from acidic byproducts of PGA degradation. However, the addition of PVA and/or chitosan into a wet-laid non-woven textile mesh from PGA improved chondrocyte proliferation seeded in vitro on the PGA-based composite scaffold namely due to a diminished acidification of their microenvironment. This PVA/PGA composite mesh used in combination with a proper hydrogel minimized the negative effect of PGA degradation without dropping positive parameters of the PGA wet-laid non-woven textile mesh. In fact, presence of PVA and/or chitosan in the PGA-based wet-laid non-woven textile mesh even advanced the PGA-based wet-laid non-woven textile mesh for chondrocyte seeding and artificial cartilage production due to a positive effect of PVA in such a scaffold on chondrocyte proliferation.

Proliferating cellular nuclear antigen expression as a marker of perivascular macrophages in simian immunodeficiency virus encephalitis.

PubMed

Williams, Kenneth; Schwartz, Annette; Corey, Sarah; Orandle, Marlene; Kennedy, William; Thompson, Brendon; Alvarez, Xavier; Brown, Charlie; Gartner, Suzanne; Lackner, Andrew

2002-08-01

Brain perivascular macrophages are a major target of simian immunodeficiency virus (SIV) infection in rhesus macaques and HIV infection in humans. Perivascular macrophages are distinct from parenchymal microglia in their location, morphology, expression of myeloid markers, and turnover in the CNS. In contrast to parenchymal microglia, perivascular macrophages are continuously repopulated by blood monocytes, which undergo maturation to macrophages on entering the central nervous system (CNS). We studied differences in monocyte/macrophages in vivo that might account for preferential infection of perivascular macrophages by SIV. In situ hybridization for SIV and proliferating cellular nuclear antigen (PCNA) immunohistochemistry demonstrated that SIV-infected and PCNA-positive cells were predominantly found in perivascular cuffs of viremic animals and in histopathological lesions that characterize SIV encephalitis (SIVE) in animals with AIDS. Multilabel techniques including double-label immunohistochemistry and combined in situ hybridization and immunofluorescence confocal microscopy revealed numerous infected perivascular macrophages that were PCNA-positive. Outside the CNS, SIV-infected, PCNA-expressing macrophage subpopulations were found in the small intestine and lung of animals with AIDS. While PCNA is used as a marker of cell proliferation it is also strongly expressed in non-dividing cells undergoing DNA synthesis and repair. Therefore, more specific markers for cell proliferation including Ki-67, topoisomerase IIalpha, and bromodeoxyuridine (BrdU) incorporation were used which indicated that PCNA-positive cells within SIVE lesions were not proliferating. These observations are consistent with perivascular macrophages as terminally differentiated, non-dividing cells and underscores biological differences that could potentially define mechanisms of preferential, productive infection of perivascular macrophages in the rhesus macaque model of neuroAIDS. These

Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eto, Masumi, E-mail: masumi.eto@jefferson.edu; Kirkbride, Jason A.; Chugh, Rishika

2013-04-26

Highlights: •Non-canonical roles of the myosin phosphatase inhibitor (CPI-17) were studied. •CPI-17 is localized in the nucleus of hyperplastic cancer and smooth muscle cells. •CPI-17 Ser12 phosphorylation may regulate the nuclear import. •CPI-17 regulates histone H3 phosphorylation and cell proliferation. •The nuclear CPI-17-PP1 axis plays a proliferative role in cells. -- Abstract: CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17 kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17 expression in proliferating cells, such as pancreatic cancer and hyperplastic SM cells. Immunofluorescence showed that CPI-17 was concentratedmore » in nuclei of human pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected in the proliferating vascular SM cell culture and cells at neointima of rat vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI-17 at Ser12 attenuated the nuclear import. CPI-17 phosphorylated at Ser12 was not localized at nuclei, suggesting a suppressive role of Ser12 phosphorylation in the nuclear import. Activated CPI-17 bound to all three isoforms of PP1 catalytic subunit in Panc1 nuclear extracts. CPI-17 knockdown in Panc1 resulted in dephosphorylation of histone H3 at Thr3, Ser10 and Thr11, whereas it had no effects on the phosphorylation of myosin light chain and merlin, the known targets of MLCP. In parallel, CPI-17 knockdown suppressed Panc1 proliferation. We propose that CPI-17 accumulated in the nucleus through the N-terminal tail targets multiple PP1 signaling pathways regulating cell proliferation.« less

DTIC review. Volume 1, Number 1: Nuclear proliferation and deterrence in a changing political world

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cupp, C.M.; Lee, C.; Foster, H.

1995-08-01

This collection of selected documents from the Defense Technical Information Center (DTIC) addresses the formidable issue of protecting the United States and its people from potential nuclear destruction. With the dissolution of the former Soviet Union and, concomitantly, the end of the Cold War, new strategies for nonproliferation and deterrence must be devised and implemented. Potential threats from countries not previously seen as a danger, the escalation of regional conflicts and the proliferation of weapons of mass destruction are but a few of the considerations to be addressed. The authors of the following papers propose various plans and tactics tomore » ensure United States national security and maintain world peace.« less

Non-Nuclear Testing of Space Nuclear Systems at NASA MSFC

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Pearson, Boise J.; Aschenbrenner, Kenneth C.; Bradley, David E.; Dickens, Ricky; Emrich, William J.; Garber, Anne; Godfroy, Thomas J.; Harper, Roger T.; Martin, Jim J.;

Improving the Nuclear Reform Implementation for Success

DTIC Science & Technology

2016-09-15

IMPROVING THE NUCLEAR REFORM IMPLEMENTATION FOR SUCCESS GRADUATE RESEARCH PAPER Allen Y. Agnes...United States. AFIT-ENS-MS-16-S-023 IMPROVING THE NUCLEAR REFORM IMPLMENTATION FOR SUCCESS GRADUATE RESEARCH PAPER Presented to the...AFIT-ENS-MS-16-S-023 IMPROVING THE NUCLEAR REFORM IMPLEMENTATION FOR SUCCESS Allen Y. Agnes, BS, MS Major, USAF

CCDC106 promotes non-small cell lung cancer cell proliferation.

PubMed

Zhang, Xiupeng; Zheng, Qin; Wang, Chen; Zhou, Haijing; Jiang, Guiyang; Miao, Yuan; Zhang, Yong; Liu, Yang; Li, Qingchang; Qiu, Xueshan; Wang, Enhua

2017-04-18

Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.

PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells

PubMed Central

Bazzani, Lorenzo; Donnini, Sandra; Giachetti, Antonio; Christofori, Gerhard; Ziche, Marina

2018-01-01

Prostaglandin E2 (PGE2) contributes to tumor progression by promoting cancer cell growth, invasion and by creating a favorable pro-tumor microenvironment. PGE2 has been reported to transactivate and internalize into the nucleus receptor tyrosine kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, PGE2 induces EGFR nuclear translocation via different dynamin-dependent endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects nuclear EGFR target gene expression and mediates tumor cell proliferation. Indeed, we find that PGE2 induces EGFR internalization and consequent nuclear import through Clathrin- and Caveolin-mediated endocytosis and through the interaction of EGFR with Importin β1. Within the nucleus, EGFR forms a complex with STAT3, an event blocked by ablation of Clathrin Heavy Chain or Caveolin-1. The combination of EGF and PGE2 prolongs nuclear EGFR transcriptional activity manifested by the upregulation of CCND1, PTGS2, MYC and NOS2 mRNA levels and potentiates nuclear EGFR-induced NSCLC cell proliferation. Additionally, NSCLC patients with high expression of a nuclear EGFR gene signature display shorter survival times than those with low expression, thus showing a putative correlation between nuclear EGFR and poor prognosis in NSCLC. Together, our findings indicate a complex mechanism underlying PGE2-induced EGF/EGFR signaling and transcriptional control, which plays a key role in cancer progression. PMID:29599917

PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells.

PubMed

Bazzani, Lorenzo; Donnini, Sandra; Giachetti, Antonio; Christofori, Gerhard; Ziche, Marina

2018-03-13

Prostaglandin E 2 (PGE 2 ) contributes to tumor progression by promoting cancer cell growth, invasion and by creating a favorable pro-tumor microenvironment. PGE 2 has been reported to transactivate and internalize into the nucleus receptor tyrosine kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, PGE 2 induces EGFR nuclear translocation via different dynamin-dependent endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects nuclear EGFR target gene expression and mediates tumor cell proliferation. Indeed, we find that PGE 2 induces EGFR internalization and consequent nuclear import through Clathrin- and Caveolin-mediated endocytosis and through the interaction of EGFR with Importin β1. Within the nucleus, EGFR forms a complex with STAT3, an event blocked by ablation of Clathrin Heavy Chain or Caveolin-1. The combination of EGF and PGE 2 prolongs nuclear EGFR transcriptional activity manifested by the upregulation of CCND1 , PTGS2 , MYC and NOS2 mRNA levels and potentiates nuclear EGFR-induced NSCLC cell proliferation. Additionally, NSCLC patients with high expression of a nuclear EGFR gene signature display shorter survival times than those with low expression, thus showing a putative correlation between nuclear EGFR and poor prognosis in NSCLC. Together, our findings indicate a complex mechanism underlying PGE 2 -induced EGF/EGFR signaling and transcriptional control, which plays a key role in cancer progression.

Proliferation dangers associated with nuclear medicine: getting weapons-grade uranium out of radiopharmaceutical production.

PubMed

Williams, Bill; Ruff, Tilman A

2007-01-01

Abolishing the threat of nuclear war requires the outlawing of nuclear weapons and dismantling current nuclear weapon stockpiles, but also depends on eliminating access to fissile material (nuclear weapon fuel). The near-universal use of weapons-grade, highly enriched uranium (HEU) to produce radiopharmaceuticals is a significant proliferation hazard. Health professionals have a strategic opportunity and obligation to progress the elimination of medically-related commerce in HEU, closing one of the most vulnerable pathways to the much-feared 'terrorist bomb'.

CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation

PubMed Central

Zhai, Hui-Hong; Meng, Juan; Wang, Jing-Bo; Liu, Zhen-Xiong; Li, Yuan-Fei; Feng, Shan-Shan

2014-01-01

AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis. METHODS: The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot. Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin. To confirm the immunofluorescence findings, the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot. The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay. The colony formation assay was used to measure clonogenic cell survival. The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated. Two CacyBP/SIP-specific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP, and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot. The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed. RESULTS: CacyBP/SIP protein was present in most of gastric cancer cell lines. In unstimulated cells, CacyBP/SIP was distributed throughout the cytoplasm; while in stimulated cells, CacyBP/SIP was found mainly in the perinuclear region. CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells. The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group. The percentage of stimulated cells in G1 phase was significantly lower than that of control cells (69.70% ± 0.46% and 65.80% ± 0.60%, control cells and gastrin-treated SGC7901 cells, P = 0.008; 72.99% ± 0.46% and 69.36% ± 0.51%, control cells and gastrin-treated MKN45 cells, P = 0.022). CacyBP/SIPsi1 effectively down-regulated the expression of CacyBP/SIP, and cells stably

CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation.

PubMed

Zhai, Hui-Hong; Meng, Juan; Wang, Jing-Bo; Liu, Zhen-Xiong; Li, Yuan-Fei; Feng, Shan-Shan

2014-08-07

To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis. The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot. Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin. To confirm the immunofluorescence findings, the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot. The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay. The colony formation assay was used to measure clonogenic cell survival. The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated. Two CacyBP/SIP-specific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP, and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot. The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed. CacyBP/SIP protein was present in most of gastric cancer cell lines. In unstimulated cells, CacyBP/SIP was distributed throughout the cytoplasm; while in stimulated cells, CacyBP/SIP was found mainly in the perinuclear region. CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells. The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group. The percentage of stimulated cells in G1 phase was significantly lower than that of control cells (69.70% ± 0.46% and 65.80% ± 0.60%, control cells and gastrin-treated SGC7901 cells, P = 0.008; 72.99% ± 0.46% and 69.36% ± 0.51%, control cells and gastrin-treated MKN45 cells, P = 0.022). CacyBP/SIPsi1 effectively down-regulated the expression of CacyBP/SIP, and cells stably transfected by Cacy

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

PubMed

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

2018-02-01

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

Nuclear proliferation: Will the Soviet Union's collapse spawn a new arms race

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffin, R.D.

Almost 30 years ago, in the midst of the US-Soviet arms race, President John F. Kennedy warned of the danger of nuclear proliferation. Ironically, now that the Cold War is over, the prospect has become a reality. The collapse of the Soviet Union may have calmed fears of a nuclear Armageddon, but it has aroused new concerns about the spread of nuclear weapons. More than a dozen nations either have or are feverishly trying to develop nuclear arsenals, including Third World nations riven by religious and territorial disputes. If the world fails to contain the spread of nuclear-weapons technology, themore » balance of power that kept relative peace during the four decades of the Cold War may be displaced by a balance of terror.« less

Reducing Proliferation Rick Through Multinational Fuel Cycle Facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amanda Rynes

2010-11-01

With the prospect of rapid expansion of the nuclear energy industry and the ongoing concern over weapons proliferation, there is a growing need for a viable alternative to traditional nation-based fuel production facilities. While some in the international community remain apprehensive, the advantages of multinational fuel cycle facilities are becoming increasingly apparent, with states on both sides of the supply chain able to garner the security and financial benefits of such facilities. Proliferation risk is minimized by eliminating the need of states to establish indigenous fuel production capabilities and the concept's structure provides an additional internationally monitored barrier against themore » misuse or diversion of nuclear materials. This article gives a brief description of the arguments for and against the implementation of a complete multinational fuel cycle.« less

Avoiding Armageddon: The US Military’s Response to Trans-Regional Nuclear Proliferation in a Post-Soviet World

DTIC Science & Technology

2016-05-26

Post -Soviet World A Monograph by MAJ Andrew S. Glenn US Army School of Advanced Military Studies United States Army Command and General...2016 4. TITLE AND SUBTITLE Avoiding Armageddon: The US Military1s Response to Trans-Regional Nuclear Proliferation in a Post -Soviet World Sa...MAJ Andrew S. Glenn Monograph Title: Avoiding Armageddon: The US Military’s Response to Trans- Regional Nuclear Proliferation in a Post -Soviet

77 FR 37261 - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... National Emergency With Respect to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons... Extracted from Nuclear Weapons, dated February 18, 1993, and related contracts and agreements (collectively... derived from nuclear weapons to low enriched uranium for peaceful commercial purposes. The order invoked...

Pakistans Nuclear Weapons

DTIC Science & Technology

2016-02-12

not be subject to International Atomic Energy Agency ( IAEA ) safeguards have the potential to produce 280...PNRA states that Pakistan follows IAEA physical protection standards. Proliferation A fundamental aspect of nuclear security is ensuring that...related to the design and fabrication of a nuclear explosive device,” according to the IAEA (Implementation of the NPT Safeguards Agreement in the

Taking a stand against nuclear proliferation: the pediatrician's role.

PubMed

Newman, Thomas B

2008-05-01

Nuclear weapons pose a grave threat to the health of children. The Nuclear Nonproliferation Treaty, which for almost 40 years has limited the spread of nuclear weapons, is in danger of unraveling. At the 2000 Nuclear Nonproliferation Treaty Review Conference, 180 countries, including the United States, agreed on 13 practical steps to implement Article VI of the treaty, which calls for nuclear disarmament. However, the United States has acted in contravention of several of those disarmament steps, with announced plans to develop new nuclear weapons and to maintain a large nuclear arsenal for decades to come. Pediatricians, working individually and through organizations such as the American Academy of Pediatrics and International Physicians for the Prevention of Nuclear War, can educate the public and elected officials regarding the devastating and irremediable effects of nuclear weapons on children and the need for policies that comply with and strengthen the Nuclear Nonproliferation Treaty, rather than undermining it. For the children of the world, our goal must be a nuclear weapons convention (similar to the chemical and biological weapons conventions) that would prohibit these weapons globally.

Non-alcoholic beverages, unknown influence on cell proliferation - an in vitro study.

PubMed

Nowacki, Maciej; Adamowicz, Jan; Olkowska, Joanna; Pietkun, Katarzyna; Kloskowski, Tomasz; Bajek, Anna; Drewa, Tomasz

2014-01-01

The aim of the presented study was to check differences between 'Diet' and 'non-Diet' soft drinks on cell proliferation. Coca Cola and Pepsi Cola of different origin and their dietetic versions were examined at concentrations of 2% and 4%. Fructose and glucose as well as medium alone (control) were examined. Cell number was higher in media supplemented with soft drinks, compared to control. Proliferation depended on the soft drink concentration and its origin, but not on sugar and calorific content. An unknown factor is responsible for the increase in proliferation.

Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.

PubMed

Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

2012-04-01

Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future.

Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells

PubMed Central

2014-01-01

Background Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied. Methods Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay. Results We observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti

miR-137 inhibits the proliferation of human non-small cell lung cancer cells by targeting SRC3

PubMed Central

Chen, Ruilin; Zhang, Yongqing; Zhang, Chengcheng; Wu, Hua; Yang, Shumei

2017-01-01

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G1/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells. Notably, miR-137 could significantly suppress SRC3 3′ untranslated region (UTR) luciferase-reporter activity, an effect that was not detectable when the putative 3′-UTR target-site was mutated, further clarifying the molecular mechanisms underlying the role of miR-137 in NSCLC. In conclusion, the results of the present study suggest that miR-137 suppresses NSCLC cell proliferation by partially targeting SRC3. PMID:28521488

Proliferation resistance of small modular reactors fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polidoro, F.; Parozzi, F.; Fassnacht, F.

2013-07-01

In this paper the proliferation resistance of different types of Small Modular Reactors (SMRs) has been examined and classified with criteria available in the literature. In the first part of the study, the level of proliferation attractiveness of traditional low-enriched UO{sub 2} and MOX fuels to be used in SMRs based on pressurized water technology has been analyzed. On the basis of numerical simulations both cores show significant proliferation risks. Although the MOX core is less proliferation prone in comparison to the UO{sub 2} core, it still can be highly attractive for diversion or undeclared production of nuclear material. Inmore » the second part of the paper, calculations to assess the proliferation attractiveness of fuel in typical small sodium cooled fast reactor show that proliferation risks from spent fuel cannot be neglected. The core contains a highly attractive plutonium composition during the whole life cycle. Despite some aspects of the design like the sealed core that enables easy detection of unauthorized withdrawal of fissile material and enhances proliferation resistance, in case of open Non-Proliferation Treaty break-out, weapon-grade plutonium in sufficient quantities could be extracted from the reactor core.« less

The Attractiveness of Materials in Advanced Nuclear Fuel Cycles for Various Proliferation and Theft Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bathke, C. G.; Wallace, R. K.; Ireland, J. R.

2010-09-01

This paper is an extension to earlier studies1,2 that examined the attractiveness of materials mixtures containing special nuclear materials (SNM) and alternate nuclear materials (ANM) associated with the PUREX, UREX, COEX, THOREX, and PYROX reprocessing schemes. This study extends the figure of merit (FOM) for evaluating attractiveness to cover a broad range of proliferant state and sub-national group capabilities. The primary conclusion of this study is that all fissile material needs to be rigorously safeguarded to detect diversion by a state and provided the highest levels of physical protection to prevent theft by sub-national groups; no “silver bullet” has beenmore » found that will permit the relaxation of current international safeguards or national physical security protection levels. This series of studies has been performed at the request of the United States Department of Energy (DOE) and is based on the calculation of "attractiveness levels" that are expressed in terms consistent with, but normally reserved for nuclear materials in DOE nuclear facilities.3 The expanded methodology and updated findings are presented. Additionally, how these attractiveness levels relate to proliferation resistance and physical security are discussed.« less

The attractiveness of materials in advanced nuclear fuel cycles for various proliferation and theft scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bathke, Charles G; Wallace, Richard K; Ireland, John R

2009-01-01

This paper is an extension to earlier studies that examined the attractiveness of materials mixtures containing special nuclear materials (SNM) and alternate nuclear materials (ANM) associated with the PUREX, UREX, COEX, THOREX, and PYROX reprocessing schemes. This study extends the figure of merit (FOM) for evaluating attractiveness to cover a broad range of proliferant state and sub-national group capabilities. The primary conclusion of this study is that all fissile material needs to be rigorously safeguarded to detect diversion by a state and provided the highest levels of physical protection to prevent theft by sub-national groups; no 'silver bullet' has beenmore » found that will permit the relaxation of current international safeguards or national physical security protection levels. This series of studies has been performed at the request of the United States Department of Energy (DOE) and is based on the calculation of 'attractiveness levels' that are expressed in terms consistent with, but normally reserved for nuclear materials in DOE nuclear facilities. The expanded methodology and updated findings are presented. Additionally, how these attractiveness levels relate to proliferation resistance and physical security are discussed.« less

CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

PubMed Central

Ganju, R K; Sunday, M; Tsarwhas, D G; Card, A; Shipp, M A

1994-01-01

The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. Images PMID:7962523

76 FR 35953 - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... Accumulation of Weapons-Useable Fissile Material in the Territory of the Russian Federation #0; #0; #0... National Emergency With Respect to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons... Extracted from Nuclear Weapons, dated February 18, 1993, and related contracts and agreements (collectively...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1979-01-19

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

Financial incentives for reducing proliferation risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weise, Rachel A.; Hund, Gretchen

This article submitted for publication to the Bulletin of Atomic Scientists explains the possible financial incentives for financial institutions and large integrators to reduce nuclear proliferation risks by including anti-proliferation measures in their due diligence and requiring their suppliers to meet heightened compliance standards. Because manufacturers of dual-use nuclear goods are diverse and numerous outreach is difficult. However, financial institutions and large integrators work with nearly all dual-use manufacturers, making financial institutions and integrators well-positioned to increase awareness of proliferation and trafficking risks throughout the nuclear supply chain

Cellular proliferation in the urorectal septation complex of the human embryo at Carnegie stages 13-18: a nuclear area-based morphometric analysis.

PubMed

Nebot-Cegarra, Josep; Fàbregas, Pere Jordi; Sánchez-Pérez, Inma

2005-10-01

In order to analyse the patterns of cellular proliferation both in the mesenchyme of the urorectal septum (URS) and in the adjacent territories (posterior urogenital mesenchyme, anterior intestinal mesenchyme and cloacal folds mesenchyme), as well as their contribution to the process of cloacal division, a computer-assisted method was used to obtain the nuclear area of 3874 mesenchymal cells from camera lucida drawings of nuclear contours of selected sections of human embryos [Carnegie stages (CSs) 13-18]. Based on changes in the size of the nucleus during the cellular cycle, we considered proliferating cells in each territory to be those with a nuclear area over the 75th percentile. The URS showed increasing cell proliferation, with proliferation patterns that coincided closely with cloacal folds mesenchyme, and with less overall proliferation than urogenital and intestinal mesenchymes. Furthermore, at CS 18, we observed the beginning of the rupture in the cloacal membrane; however, no fusion has been demonstrated either between the URS and the cloacal membrane or between the cloacal folds. The results suggest that cloacal division depends on a morphogenetic complex where the URS adjacent territories could determine septal displacement at the time that their mesenchymes could be partially incorporated within the proliferating URS.

Non-Nuclear Testing of Fission Technologies at NASA MSFC

NASA Technical Reports Server (NTRS)

Houts, Robert G.; Pearson, J. Boise; Aschenbrenner, Kenneth C.; Bradley, David E.; Dickens, Ricky E.; Emrich, William J.; Garber, Anne E.; Godfroy, Thomas J.; Harper, Roger T.; Martin, Jim J.;

THE ATTRACTIVENESS OF MATERIALS IN ADVANCED NUCLEAR FUEL CYCLES FOR VARIOUS PROLIFERATION AND THEFT SCENARIOS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bathke, C. G.; Ebbinghaus, Bartley B.; Collins, Brian A.

2012-08-29

We must anticipate that the day is approaching when details of nuclear weapons design and fabrication will become common knowledge. On that day we must be particularly certain that all special nuclear materials (SNM) are adequately accounted for and protected and that we have a clear understanding of the utility of nuclear materials to potential adversaries. To this end, this paper examines the attractiveness of materials mixtures containing SNM and alternate nuclear materials associated with the plutonium-uranium reduction extraction (Purex), uranium extraction (UREX), coextraction (COEX), thorium extraction (THOREX), and PYROX (an electrochemical refining method) reprocessing schemes. This paper provides amore » set of figures of merit for evaluating material attractiveness that covers a broad range of proliferant state and subnational group capabilities. The primary conclusion of this paper is that all fissile material must be rigorously safeguarded to detect diversion by a state and must be provided the highest levels of physical protection to prevent theft by subnational groups; no 'silver bullet' fuel cycle has been found that will permit the relaxation of current international safeguards or national physical security protection levels. The work reported herein has been performed at the request of the U.S. Department of Energy (DOE) and is based on the calculation of 'attractiveness levels' that are expressed in terms consistent with, but normally reserved for, the nuclear materials in DOE nuclear facilities. The methodology and findings are presented. Additionally, how these attractiveness levels relate to proliferation resistance and physical security is discussed.« less

Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix.

PubMed

Yun, Jing-Ping; Chew, Eng Ching; Liew, Choong-Tsek; Chan, John Y H; Jin, Mei-Lin; Ding, Ming-Xiao; Fai, Yam Hin; Li, H K Richard; Liang, Xiao-Man; Wu, Qiu-Liang

2003-12-15

It has become obvious that a better understanding and potential elucidation of the nucleolar phosphoprotein B23 involving in functional interrelationship between nuclear organization and gene expression. In present study, protein B23 expression were investigated in the regenerative hepatocytes at different periods (at days 0, 1, 2, 3, 4, 7) during liver regeneration after partial hepatectomy on the rats with immunohistochemistry and Western blot analysis. Another experiment was done with immunolabeling methods and two-dimensional (2-D) gel electrophoresis for identification of B23 in the regenerating hepatocytes and HepG2 cells (hepatoblastoma cell line) after sequential extraction with detergents, nuclease, and salt. The results showed that its expression in the hepatocytes had a locative move and quantitative change during the process of liver regeneration post-operation. Its immunochemical localization in the hepatocytes during the process showed that it moved from nucleoli of the hepatocytes in the stationary stage to nucleoplasm, cytoplasm, mitotic spindles, and mitotic chromosomes of the hepatocytes in the regenerating livers. It was quantitatively increased progressively to peak level at day 3 post-operation and declined gradually to normal level at day 7. It was detected in nuclear matrix protein (NMP) composition extracted from the regenerating hepatocytes and HepG2 cells and identified with isoelectric point (pI) value of 5.1 and molecular weight of 40 kDa. These results indicated that B23 was a proliferate shuttle protein involving in cell cycle and cell proliferation associated with nuclear matrix. Copyright 2003 Wiley-Liss, Inc.

DOE Non-Proliferation Experiment includes seismic data

NASA Astrophysics Data System (ADS)

Zucca, Jay

The U.S. Department of Energy detonated approximately 1.29 million kg of a commercial blasting agent, based on ammonium nitrate and fuel oil (ANFO), at the Nevada Test Site (NTS) on September 22, 1993, at 00:01.080 a.m. Pacific Daylight Time. The blasting agent was emplaced in a cylindrical chamber, approximately 15.2 m in diameter × 5.5 m high, located at 37.20193°N and 116.20986°E in a Rainier Mesa tunnel, 390 m underground. Code-named the Non-Proliferation Experiment (NPE), the explosion had an energy release of approximately 1 kt (1 kiloton = 4.186×1012 joules).

Nuclear Energy Present and Future

NASA Astrophysics Data System (ADS)

Hutchinson, I. H.

2006-10-01

Nuclear power plants currently generate about 20% of US and 17% of world electricity, which makes nuclear the largest non-emitting energy source in current use. Concerns about global climate change have led to a remarkable transformation of attitudes towards nuclear energy. There remain key challenges that must be faced when considering expansion of its contribution. In summary they are: Economics, Safety, Waste Disposal, and Proliferation. Electricity from legacy fission plants is highly competitive with fossil, but perceived financial risks make the large capital cost fraction a key hurdle to new-construction, and costs of 2 per installed Watt electrical are currently considered only just economically attractive. Proliferation of nuclear-weapons-enabling technology is a major concern for global stability, in which fusion may have significant technical advantages over fission. But proliferation control requires a combination of both technical and political initiatives. The feasibility of supplying process heat or hydrogen from nuclear energy inspires additional research into novel reactor concepts and associated technologies. The presentation will lay out this overall context of the nuclear energy renaissance.

UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation.

PubMed

Kim, Mihwa; Morales, Liza D; Baek, Minwoo; Slaga, Thomas J; DiGiovanni, John; Kim, Dae Joon

2017-10-31

Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. However, inhibition of AKT blocked nuclear translocation of TC45 and 14-3-3σ. Site-directed mutagenesis of 14-3-3σ binding sites within TC45 showed that a substitution at Threonine 179 (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic TC45 due to the disruption of the direct binding between TC45 and 14-3-3σ. Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB-induced apoptosis which corresponded to an increase in nuclear phosphorylated STAT3, and cell proliferation was higher in TC45/T179A-overexpressing keratinocytes compared to control keratinocytes following UVB irradiation. Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear translocation, indicating that both T179 and NLSII are required. Taken together, our findings suggest that AKT and 14-3-3σ cooperatively regulate TC45 nuclear translocation in a critical step of an early protective mechanism against UVB exposure that signals the deactivation of STAT3 in order to promote keratinocyte cell death and inhibit keratinocyte proliferation.

Cellular proliferation in the urorectal septation complex of the human embryo at Carnegie stages 13–18: a nuclear area-based morphometric analysis

PubMed Central

Nebot-Cegarra, Josep; Fàbregas, Pere Jordi; Sánchez-Pérez, Inma

2005-01-01

In order to analyse the patterns of cellular proliferation both in the mesenchyme of the urorectal septum (URS) and in the adjacent territories (posterior urogenital mesenchyme, anterior intestinal mesenchyme and cloacal folds mesenchyme), as well as their contribution to the process of cloacal division, a computer-assisted method was used to obtain the nuclear area of 3874 mesenchymal cells from camera lucida drawings of nuclear contours of selected sections of human embryos [Carnegie stages (CSs) 13–18]. Based on changes in the size of the nucleus during the cellular cycle, we considered proliferating cells in each territory to be those with a nuclear area over the 75th percentile. The URS showed increasing cell proliferation, with proliferation patterns that coincided closely with cloacal folds mesenchyme, and with less overall proliferation than urogenital and intestinal mesenchymes. Furthermore, at CS 18, we observed the beginning of the rupture in the cloacal membrane; however, no fusion has been demonstrated either between the URS and the cloacal membrane or between the cloacal folds. The results suggest that cloacal division depends on a morphogenetic complex where the URS adjacent territories could determine septal displacement at the time that their mesenchymes could be partially incorporated within the proliferating URS. PMID:16191164

Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2009-06-01

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

Growth fraction in non-small cell lung cancer estimated by proliferating cell nuclear antigen and comparison with Ki-67 labeling and DNA flow cytometry data.

PubMed Central

Fontanini, G.; Pingitore, R.; Bigini, D.; Vignati, S.; Pepe, S.; Ruggiero, A.; Macchiarini, P.

1992-01-01

Results generated by the immunohistochemical staining with PC10, a new monoclonal antibody recognizing PCNA (a nuclear protein associated with cell proliferation) in formalin-fixed and paraffin-embedded tissue were compared with those of Ki-67 labeling and DNA flow cytometry in 47 consecutive non-small cell lung cancer (NSCLC). PCNA reactivity was observed in all samples and confined to the nuclei of cancer cells. Its frequency ranged from 0 to 80% (37.7 +/- 23.6) and larger sized, early-staged and DNA aneuploid tumors expressed a significant higher number of PCNA-reactive cells. The PCNA and Ki-67 labeling rates were closely correlated (r = 0.383, P = 0.009). By flow cytometry, we observed a good correlation among PCNA labeling and S-phase fraction (r = 0.422, P = .0093) and G1 phase (r = 0.303, P = .051) of the cell cycle. Results indicate that PCNA labeling with PC10 is a simple method for assessing the proliferative activity in formalin-fixed, paraffin-embedded tissue of NSCLC and correlates well with Ki-67 labeling and S-phase fraction of the cell cycle. Images Figure 2 PMID:1361306

Evaluating the Cost, Safety, and Proliferation Risks of Small Floating Nuclear Reactors.

PubMed

Ford, Michael J; Abdulla, Ahmed; Morgan, M Granger

2017-11-01

It is hard to see how our energy system can be decarbonized if the world abandons nuclear power, but equally hard to introduce the technology in nonnuclear energy states. This is especially true in countries with limited technical, institutional, and regulatory capabilities, where safety and proliferation concerns are acute. Given the need to achieve serious emissions mitigation by mid-century, and the multidecadal effort required to develop robust nuclear governance institutions, we must look to other models that might facilitate nuclear plant deployment while mitigating the technology's risks. One such deployment paradigm is the build-own-operate-return model. Because returning small land-based reactors containing spent fuel is infeasible, we evaluate the cost, safety, and proliferation risks of a system in which small modular reactors are manufactured in a factory, and then deployed to a customer nation on a floating platform. This floating small modular reactor would be owned and operated by a single entity and returned unopened to the developed state for refueling. We developed a decision model that allows for a comparison of floating and land-based alternatives considering key International Atomic Energy Agency plant-siting criteria. Abandoning onsite refueling is beneficial, and floating reactors built in a central facility can potentially reduce the risk of cost overruns and the consequences of accidents. However, if the floating platform must be built to military-grade specifications, then the cost would be much higher than a land-based system. The analysis tool presented is flexible, and can assist planners in determining the scope of risks and uncertainty associated with different deployment options. © 2017 Society for Risk Analysis.

[Effects of non-saccharomyces albicans metabolic products on the proliferation of human umbilical vein endothelial cell ECV304].

PubMed

Chen, Bin; Che, Tuanjie; Bai, Decheng; He, Xiangyi

2013-04-01

To evaluate the effects of non-Saccharomyces albicans metabolic products on the cell cycle distribution and proliferation of human umbilical vein endothelial cell ECV304 cells in vitro. The parallel dilution supernatant of Saccharomyces tropicalis, Saccharomyces krusei and Saccharomyces glabrata were prepared, and 1, 4, 16-fold(s) diluted concentration and control group were set up. The line of human umbilical vein endothelial cell ECV304 was cultured in vitro and treated by non-Saccharomyces albicans supernatant. The proliferous effect of ECV304 induced by non-Saccharomyces albicans supernatant after 24, 48, 72 h was detected by the methods of MTT, and the changes of cell density and cycle after 48 h were investigated by inverted microscope and flow cytometry. At the 24th hour, all of the higher concentration (1-fold) of non-Saccharomyces albicans supernatant and the 4-folds diluted Saccharomyces krusei could promote ECV304 proliferation(P < 0.05). After adding various non-Saccharomyces albicans supernatant at 48h and 72th hour, Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant significantly increased proliferation rate of ECV304, while Saccharomyces tropicalis supernatant group showed no significant change no matter which concentration was tested. At 48th hour after adding the non-Saccharomyces albicans supernatant, the ECV304 cells density treated by Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant were significantly higher under the inverted microscope. The G0/G1 population of ECV304 cells decreased while cell proliferation index (PI) increased after incubated with Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant for 48 hours (P < 0.05). Saccharomyces tropicalis group showed no significant change (P > 0.05). The metabolic products of Sacharoymces krusei and Saccharomyces glabrata could induce proliferation of ECV304 cell, which suggests non-Saccharomyces albicans should be undergone more

Nuclear nonproliferation: India Pakistan. Research report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fallon, J.S.

1997-04-01

As most of the world continues to seek ways to reduce or eliminate the spread of nuclear weapons, two countries seem intent on pursuing a path which is contradictory. India and Pakistan, two neighboring and frequently warring nations, condemn the use of nuclear weapons as they continue to develop the capability to deliver a nuclear payload. Additionally, India has stood against the Non-Proliferation Treaty, insisting that all nations must agree to eliminate nuclear weapons. It is against this seemingly hopeless situation that this report is focused. How can nuclear proliferation in South Asia be diffused while answering the security concernsmore » of both India and Pakistan. What I offer here is a review of the history, the current situation for the area, and a proposed solution to this nuclear stalemate.« less

Nuclear accumulation of SHIP1 mutants derived from AML patients leads to increased proliferation of leukemic cells.

PubMed

Nalaskowski, Marcus M; Ehm, Patrick; Rehbach, Christoph; Nelson, Nina; Täger, Maike; Modest, Kathrin; Jücker, Manfred

2018-05-28

The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis. After relocalization from the cytoplasm to the plasma membrane SHIP1 terminates PI3-kinase mediated signaling processes. Furthermore, SHIP1 is also found in distinct puncta in the cell nucleus and nuclear SHIP1 has a pro-proliferative function. Here we report the identification of five nuclear export signals (NESs) which regulate together with the two known nuclear localization signals (NLSs) the nucleocytoplasmic shuttling of SHIP1. Mutation of NLSs reduced the nuclear import and mutation of NESs decreased the nuclear export of SHIP1 in the acute myeloid leukemia (AML) cell line UKE-1. Interestingly, four SHIP1 mutants (K210R, N508D, V684E, Q1153L) derived from AML patients showed a nuclear accumulation after expression in UKE-1 cells. In addition, overexpression of the AML patient-derived mutation N508D caused an increased proliferation rate of UKE-1 cells in comparison to wild type SHIP1. Furthermore, we identified serine and tyrosine phosphorylation as a molecular mechanism for the regulation of nucleocytoplasmic shuttling of SHIP1 where tyrosine phosphorylation of distinct residues i.e. Y864, Y914, Y1021 reduces nuclear localization, whereas serine phosphorylation at S933 enhances nuclear localization of SHIP1. In summary, our data further implicate nuclear SHIP1 in cellular signaling and suggest that enhanced accumulation of SHIP1 mutants in the nucleus may be a contributory factor of abnormally high proliferation of AML cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Nuclear weapons modernizations

NASA Astrophysics Data System (ADS)

Kristensen, Hans M.

2014-05-01

This article reviews the nuclear weapons modernization programs underway in the world's nine nuclear weapons states. It concludes that despite significant reductions in overall weapons inventories since the end of the Cold War, the pace of reductions is slowing - four of the nuclear weapons states are even increasing their arsenals, and all the nuclear weapons states are busy modernizing their remaining arsenals in what appears to be a dynamic and counterproductive nuclear competition. The author questions whether perpetual modernization combined with no specific plan for the elimination of nuclear weapons is consistent with the nuclear Non-Proliferation Treaty and concludes that new limits on nuclear modernizations are needed.

Nuclear Proliferation Factbook. Prepared for the Subcommittees on Arms Control, International Security and Science and on International Economic Policy and Trade of the Committee on Foreign Affairs, U.S. House of Representatives and the Subcommittee on Energy, Nuclear Proliferation, and Federal Processes of the Committee on Governmental Affairs, U.S. Senate, 99th Congress, 1st session.

ERIC Educational Resources Information Center

Library of Congress, Washington, DC. Congressional Research Service.

To provide a handy reference for those concerned with ways to avoid the further spread, or proliferation, of nuclear weapons, the House Committee on Foreign Affairs and the Senate Committee on Governmental Affairs have since 1977 sponsored periodic publication of the Nuclear Proliferation Factbook. This fourth edition of the factbook includes a…

15 CFR 742.3 - Nuclear nonproliferation.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.3 Nuclear nonproliferation. (a) License requirements. Section 309(c) of the Nuclear Non-Proliferation Act of 1978 requires BIS to identify items subject to the EAR that could be of...

15 CFR 742.3 - Nuclear nonproliferation.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.3 Nuclear nonproliferation. (a) License requirements. Section 309(c) of the Nuclear Non-Proliferation Act of 1978 requires BIS to identify items subject to the EAR that could be of...

15 CFR 742.3 - Nuclear nonproliferation.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.3 Nuclear nonproliferation. (a) License requirements. Section 309(c) of the Nuclear Non-Proliferation Act of 1978 requires BIS to identify items subject to the EAR that could be of...

15 CFR 742.3 - Nuclear nonproliferation.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.3 Nuclear nonproliferation. (a) License requirements. Section 309(c) of the Nuclear Non-Proliferation Act of 1978 requires BIS to identify items subject to the EAR that could be of...

15 CFR 742.3 - Nuclear nonproliferation.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.3 Nuclear nonproliferation. (a) License requirements. Section 309(c) of the Nuclear Non-Proliferation Act of 1978 requires BIS to identify items subject to the EAR that could be of...

Nuclear exports: the perilous enterprise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, G.

1977-03-01

A representative of the Sierra Club proposes that the United States can at least provide an opportunity for a break in the trend toward nuclear proliferation and may be able to offer the moral and economic persuasion for a worldwide moratorium. The combination of plutonium toxicity and its use in making nuclear explosives, together with the number of countries who have recently entered the nuclear community, indicate an increasing problem in limiting nuclear power to peaceful purposes. The ease with which plutonium can be diverted from power-generating plants into the hands of terrorists and unstable rulers limits the security options.more » The non-proliferation agreements are felt to have created additional problems by making it possible for non-signers of the treaty to have less-stringent safeguards than the signers. The International Atomic Energy Agency is considered to be effective only in a bookkeeping and monitoring capacity, while competition between nuclear suppliers may lead them to relax standards. The author feels that efforts to negotiate voluntary restraints on exporters could offer guarantees of fuel services and other nuclear assistance to those countries agreeing to forego nuclear explosives and reprocessing facilities and accepting safeguards restraints and export restrictions. (DCK)« less

The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases

PubMed Central

Tyagi, Sandeep; Gupta, Paras; Saini, Arminder Singh; Kaushal, Chaitnya; Sharma, Saurabh

2011-01-01

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of the following three subtypes: PPARα, PPARγ, and PPARβ/δ. Activation of PPAR-α reduces triglyceride level and is involved in regulation of energy homeostasis. Activation of PPAR-γ causes insulin sensitization and enhances glucose metabolism, whereas activation of PPAR-β/δ enhances fatty acids metabolism. Thus, PPAR family of nuclear receptors plays a major regulatory role in energy homeostasis and metabolic function. The present review critically analyzes the protective and detrimental effect of PPAR agonists in dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. PMID:22247890

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity.

PubMed

Linnemann, Amelia K; Krawetz, Stephen A

2009-05-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14-18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment.

Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells.

PubMed

Shi, Xiaoli; Xiong, Xiaokan; Dai, Zhe; Deng, Haohua; Sun, Li; Hu, Xuemei; Zhou, Feng; Xu, Yancheng

Nuclear orphan receptor TLX is an essential regulator of the growth of neural stem cells. However, its exact function in pancreatic islet cells is still unknown. In the present study, gene expression profiling analysis revealed that overexpression of TLX in beta cell line MIN6 causes suppression of 176 genes and upregulation of 49 genes, including a cadre of cell cycle, cell proliferation and cell death control genes, such as Btg2, Ddit3 and Gadd45a. We next examined the effects of TLX overexpression on proliferation, apoptosis and insulin secretion in MIN6 cells. Proliferation analysis using EdU assay showed that overexpression of TLX increased percentage of EdU-positive cells. Cell cycle and apoptosis analysis revealed that overexpression of TLX in MIN6 cells resulted in higher percentage of cells exiting G1 into S-phase, and a 58.8% decrease of cell apoptosis induced by 0.5 mM palmitate. Moreover, TLX overexpression did not cause impairment of insulin secretion. Together, we conclude that TLX is among factors capable of controlling beta cell proliferation and survival, which may serve as a target for the development of novel therapies for diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

Nuclear weapons modernizations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristensen, Hans M.

This article reviews the nuclear weapons modernization programs underway in the world's nine nuclear weapons states. It concludes that despite significant reductions in overall weapons inventories since the end of the Cold War, the pace of reductions is slowing - four of the nuclear weapons states are even increasing their arsenals, and all the nuclear weapons states are busy modernizing their remaining arsenals in what appears to be a dynamic and counterproductive nuclear competition. The author questions whether perpetual modernization combined with no specific plan for the elimination of nuclear weapons is consistent with the nuclear Non-Proliferation Treaty and concludesmore » that new limits on nuclear modernizations are needed.« less

Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xiaoli; Xiong, Xiaokan; Dai, Zhe

2015-12-04

Nuclear orphan receptor TLX is an essential regulator of the growth of neural stem cells. However, its exact function in pancreatic islet cells is still unknown. In the present study, gene expression profiling analysis revealed that overexpression of TLX in beta cell line MIN6 causes suppression of 176 genes and upregulation of 49 genes, including a cadre of cell cycle, cell proliferation and cell death control genes, such as Btg2, Ddit3 and Gadd45a. We next examined the effects of TLX overexpression on proliferation, apoptosis and insulin secretion in MIN6 cells. Proliferation analysis using EdU assay showed that overexpression of TLXmore » increased percentage of EdU-positive cells. Cell cycle and apoptosis analysis revealed that overexpression of TLX in MIN6 cells resulted in higher percentage of cells exiting G1 into S-phase, and a 58.8% decrease of cell apoptosis induced by 0.5 mM palmitate. Moreover, TLX overexpression did not cause impairment of insulin secretion. Together, we conclude that TLX is among factors capable of controlling beta cell proliferation and survival, which may serve as a target for the development of novel therapies for diabetes. - Highlights: • TLX overexpression in MIN6 cell causes significant expression changes of 225 genes. • TLX overexpression promotes MIN6 cell proliferation and decreases cell apoptosis. • TLX overexpression does not cause impairment of insulin secretion.« less

Persistence of γ-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to γ-rays or iron ions.

PubMed

Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V; Helen Barcellos-Hoff, Mary; Parvin, Bahram; Rydberg, Bjorn

2011-07-01

To investigate γ-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionising radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced γ-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both γ-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after γ-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. The disappearance of radiation-induced γ-H2AX and 53BP1 foci in HMEC has different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent γ-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double-strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodelling.

The nuclear dilemma and the just war tradition

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Brien, W.V.; Langan, J.

This book presents papers on the ethical aspects of nuclear weapons. Topics considered include the concept of a ''just'' war, national defense, political aspects, religion and politics, the failure of deterrence, conventional warfare, nuclear deterrence and democratic politics, the future of the nuclear debate, non-proliferation policy, arms control, national security, and government policies.

Path-integral isomorphic Hamiltonian for including nuclear quantum effects in non-adiabatic dynamics

NASA Astrophysics Data System (ADS)

Tao, Xuecheng; Shushkov, Philip; Miller, Thomas F.

2018-03-01

We describe a path-integral approach for including nuclear quantum effects in non-adiabatic chemical dynamics simulations. For a general physical system with multiple electronic energy levels, a corresponding isomorphic Hamiltonian is introduced such that Boltzmann sampling of the isomorphic Hamiltonian with classical nuclear degrees of freedom yields the exact quantum Boltzmann distribution for the original physical system. In the limit of a single electronic energy level, the isomorphic Hamiltonian reduces to the familiar cases of either ring polymer molecular dynamics (RPMD) or centroid molecular dynamics Hamiltonians, depending on the implementation. An advantage of the isomorphic Hamiltonian is that it can easily be combined with existing mixed quantum-classical dynamics methods, such as surface hopping or Ehrenfest dynamics, to enable the simulation of electronically non-adiabatic processes with nuclear quantum effects. We present numerical applications of the isomorphic Hamiltonian to model two- and three-level systems, with encouraging results that include improvement upon a previously reported combination of RPMD with surface hopping in the deep-tunneling regime.

University-level Non-proliferation and Safeguards Education and Human Capital Development Activities at Brookhaven National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachner K. M.; Pepper, S.; Gomera, J.

BNL has offered Nuclear Nonproliferation, Safeguards and Security in the 21st Century,? referred to as NNSS, every year since 2009 for graduate students in technical and policy fields related to nuclear safeguards and nonproliferation. The course focuses on relevant policy issues, in addition to technical components, and is part of a larger NGSI short course initiative that includes separate courses that are delivered at three other national laboratories and NNSA headquarters. [SCHOLZ and ROSENTHAL] The course includes lectures from esteemed nonproliferation experts, tours of various BNL facilities and laboratories, and in-field and table-top exercises on both technical and policy subjects.more » Topics include the history of the Treaty on the Non-proliferation of Nuclear Weapons (NPT) and other relevant treaties, the history of and advances in international nuclear safeguards, current relevant political situations in countries such as Iran, Iraq, and the Democratic Peoples? Republic of Korea (DPRK), nuclear science and technology, instrumentation and techniques used for verification activities, and associated research and development. The students conduct a mock Design Information Verification (DIV) at BNL?s decommissioned Medical Research Reactor. The capstone of the course includes a series of student presentations in which students act as policy advisors and provide recommendations in response to scenarios involving a current nonproliferation related event that are prepared by the course organizers. ?The course is open to domestic and foreign students, and caters to students in, entering, or recently having completed graduate school. Interested students must complete an application and provide a resume and a statement describing their interest in the course. Eighteen to 22 students attend annually; 165 students have completed the course to date. A stipend helps to defray students? travel and subsistence expenses. In 2015, the course was shortened from three

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity

PubMed Central

Linnemann, Amelia K.; Krawetz, Stephen A.

2009-01-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14–18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment. PMID:19276204

Proliferation of Small Nuclear Forces.

DTIC Science & Technology

1983-04-30

character of conflict, arm control issues, conventional arms competition and U.S. forces; 3) Assess how new nuclear powers will behave and how their...neighbors 0and other nuclear powers will react; "--- 5) Identify the likely patterns and outcars of nuclear and other military interaction, including...Regional Nuclear Powers , 1990-2010 A small nuclear force (SNF) would comprise at a minimum from 5 to 10 deliverable and militarily serviceable fission

RNA sequencing-based cell proliferation analysis across 19 cancers identifies a subset of proliferation-informative cancers with a common survival signature.

PubMed

Ramaker, Ryne C; Lasseigne, Brittany N; Hardigan, Andrew A; Palacio, Laura; Gunther, David S; Myers, Richard M; Cooper, Sara J

2017-06-13

Despite advances in cancer diagnosis and treatment strategies, robust prognostic signatures remain elusive in most cancers. Cell proliferation has long been recognized as a prognostic marker in cancer, but the generation of comprehensive, publicly available datasets allows examination of the links between cell proliferation and cancer characteristics such as mutation rate, stage, and patient outcomes. Here we explore the role of cell proliferation across 19 cancers (n = 6,581 patients) by using tissue-based RNA sequencing data from The Cancer Genome Atlas Project and calculating a 'proliferative index' derived from gene expression associated with Proliferating Cell Nuclear Antigen (PCNA) levels. This proliferative index is significantly associated with patient survival (Cox, p-value < 0.05) in 7 of 19 cancers, which we have defined as "proliferation-informative cancers" (PICs). In PICs, the proliferative index is strongly correlated with tumor stage and nodal invasion. PICs demonstrate reduced baseline expression of proliferation machinery relative to non-PICs. Additionally, we find the proliferative index is significantly associated with gross somatic mutation burden (Spearman, p = 1.76 x 10-23) as well as with mutations in individual driver genes. This analysis provides a comprehensive characterization of tumor proliferation indices and their association with disease progression and prognosis in multiple cancer types and highlights specific cancers that may be particularly susceptible to improved targeting of this classic cancer hallmark.

Thioredoxin (Trxo1) interacts with proliferating cell nuclear antigen (PCNA) and its overexpression affects the growth of tobacco cell culture.

PubMed

Calderón, Aingeru; Ortiz-Espín, Ana; Iglesias-Fernández, Raquel; Carbonero, Pilar; Pallardó, Federico Vicente; Sevilla, Francisca; Jiménez, Ana

2017-04-01

Thioredoxins (Trxs), key components of cellular redox regulation, act by controlling the redox status of many target proteins, and have been shown to play an essential role in cell survival and growth. The presence of a Trx system in the nucleus has received little attention in plants, and the nuclear targets of plant Trxs have not been conclusively identified. Thus, very little is known about the function of Trxs in this cellular compartment. Previously, we studied the intracellular localization of PsTrxo1 and confirmed its presence in mitochondria and, interestingly, in the nucleus under standard growth conditions. In investigating the nuclear function of PsTrxo1 we identified proliferating cellular nuclear antigen (PCNA) as a PsTrxo1 target by means of affinity chromatography techniques using purified nuclei from pea leaves. Such protein-protein interaction was corroborated by dot-blot and bimolecular fluorescence complementation (BiFC) assays, which showed that both proteins interact in the nucleus. Moreover, PsTrxo1 showed disulfide reductase activity on previously oxidized recombinant PCNA protein. In parallel, we studied the effects of PsTrxo1 overexpression on Tobacco Bright Yellow-2 (TBY-2) cell cultures. Microscopy and flow-cytometry analysis showed that PsTrxo1 overexpression increases the rate of cell proliferation in the transformed lines, with a higher percentage of the S phase of the cell cycle at the beginning of the cell culture (days 1 and 3) and at the G2/M phase after longer times of culture (day 9), coinciding with an upregulation of PCNA protein. Furthermore, in PsTrxo1 overexpressed cells there is a decrease in the total cellular glutathione content but maintained nuclear GSH accumulation, especially at the end of the culture, which is accompanied by a higher mitotic index, unlike non-overexpressing cells. These results suggest that Trxo1 is involved in the cell cycle progression of TBY-2 cultures, possibly through its link with cellular PCNA

Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation.

PubMed

Walesky, Chad; Gunewardena, Sumedha; Terwilliger, Ernest F; Edwards, Genea; Borude, Prachi; Apte, Udayan

2013-01-01

Hepatocyte nuclear factor-4α (HNF4α) is known as the master regulator of hepatocyte differentiation. Recent studies indicate that HNF4α may inhibit hepatocyte proliferation via mechanisms that have yet to be identified. Using a HNF4α knockdown mouse model based on delivery of inducible Cre recombinase via an adeno-associated virus 8 viral vector, we investigated the role of HNF4α in the regulation of hepatocyte proliferation. Hepatocyte-specific deletion of HNF4α resulted in increased hepatocyte proliferation. Global gene expression analysis showed that a majority of the downregulated genes were previously known HNF4α target genes involved in hepatic differentiation. Interestingly, ≥500 upregulated genes were associated with cell proliferation and cancer. Furthermore, we identified potential negative target genes of HNF4α, many of which are involved in the stimulation of proliferation. Using chromatin immunoprecipitation analysis, we confirmed binding of HNF4α at three of these genes. Furthermore, overexpression of HNF4α in mouse hepatocellular carcinoma cells resulted in a decrease in promitogenic gene expression and cell cycle arrest. Taken together, these data indicate that, apart from its role in hepatocyte differentiation, HNF4α actively inhibits hepatocyte proliferation by repression of specific promitogenic genes.

2015 Nuclear Fusion Prize acceptance speech

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldston, R. J.

This is the 2015 Nuclear Fusion Prize acceptance speech of R.J. Goldston: It is a great pleasure to receive the 2015 Nuclear Fusion award for my work developing a heuristic drift-based model for the power scrape-off width in tokamaks. I was particularly pleased to receive the award from IAEA Director General Yukiya Amano, whose thoughtful leadership has advanced the cause of nuclear non-proliferation mightily.

2015 Nuclear Fusion Prize acceptance speech

DOE PAGES

Goldston, R. J.

2016-12-19

This is the 2015 Nuclear Fusion Prize acceptance speech of R.J. Goldston: It is a great pleasure to receive the 2015 Nuclear Fusion award for my work developing a heuristic drift-based model for the power scrape-off width in tokamaks. I was particularly pleased to receive the award from IAEA Director General Yukiya Amano, whose thoughtful leadership has advanced the cause of nuclear non-proliferation mightily.

3 CFR - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 3 The President 1 2010-01-01 2010-01-01 false Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons-Useable Fissile Material in the Territory of the Russian Federation Presidential Documents Other Presidential Documents Notice of June 18, 2009 Continuation of the National...

3 CFR - Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Continuation of the National Emergency With Respect to the Risk of Nuclear Proliferation Created by the Accumulation of Weapons-Usable Fissile Material in the Territory of the Russian Federation Presidential Documents Other Presidential Documents Notice of June 17, 2011 Continuation of the National...

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling

PubMed Central

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-01-01

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation. PMID:20133835

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.

PubMed

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-02-02

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation.

PubMed

Sun, Guoqiang; Yu, Ruth T; Evans, Ronald M; Shi, Yanhong

2007-09-25

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359-385, which contains a conserved nuclear receptor-coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1)(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX-HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX-HDAC interactions.

Conventional and Non-Conventional Nuclear Material Signatures

NASA Astrophysics Data System (ADS)

Gozani, Tsahi

2009-03-01

The detection and interdiction of concealed special nuclear material (SNM) in all modes of transport is one of the most critical security issues facing the United States and the rest of the world. In principle, detection of nuclear materials is relatively easy because of their unique properties: all of them are radioactive and all emit some characteristic gamma rays. A few emit neutrons as well. These signatures are the basis for passive non-intrusive detection of nuclear materials. The low energy of the radiations necessitates additional means of detection and validation. These are provided by high-energy x-ray radiography and by active inspection based on inducing nuclear reactions in the nuclear materials. Positive confirmation that a nuclear material is present or absent can be provided by interrogation of the inspected object with penetrating probing radiation, such as neutrons and photons. The radiation induces specific reactions in the nuclear material yielding, in turn, penetrating signatures which can be detected outside the inspected object. The "conventional" signatures are first and foremost fission signatures: prompt and delayed neutrons and gamma rays. Their intensity (number per fission) and the fact that they have broad energy (non-discrete, though unique) distributions and certain temporal behaviors are key to their use. The "non- conventional" signatures are not related to the fission process but to the unique nuclear structure of each element or isotope in nature. This can be accessed through the excitation of isotopic nuclear levels (discrete and continuum) by neutron inelastic scattering or gamma resonance fluorescence. Finally there is an atomic signature, namely the high atomic number (Z>74), which obviously includes all the nuclear materials and their possible shielding. The presence of such high-Z elements can be inferred by techniques using high-energy x rays. The conventional signatures have been addressed in another article. Non

Phospholipase C delta 4 (PLCδ4) is a nuclear protein involved in cell proliferation and senescence in mesenchymal stromal stem cells.

PubMed

Kunrath-Lima, Marianna; de Miranda, Marcelo Coutinho; Ferreira, Andrea da Fonseca; Faraco, Camila Cristina Fraga; de Melo, Mariane Izabella Abreu; Goes, Alfredo Miranda; Rodrigues, Michele Angela; Faria, Jerusa Araújo Quintão Arantes; Gomes, Dawidson Assis

2018-06-01

Ca 2+ is an important second messenger, and it is involved in many cellular processes such as cell death and proliferation. The rise in intracellular Ca 2+ levels can be due to the generation of inositol 1,4,5-trisphosphate (InsP 3 ), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) hydrolysis by phospholipases C (PLCs), that leads to Ca 2+ release from endoplasmic reticulum by InsP 3 receptors (InsP 3 R). Ca 2+ signaling patterns can vary in different regions of the cell and increases in nuclear Ca 2+ levels have specific biological effects that differ from those of Ca 2+ increase in the cytoplasm. There are PLCs in the cytoplasm and nucleus, but little is known about the functions of nuclear PLCs. This work aimed to characterize phenotypically the human PLCδ4 (hPLCδ4) in mesenchymal stem cells. This nuclear isoform of PLC is present in different cell types and has a possible role in proliferative processes. In this work, hPLCδ4 was found to be mainly nuclear in human adipose-derived mesenchymal stem cells (hASC). PLCδ4 knockdown demonstrated that it is essential for hASC proliferation, without inducing cell death. An increase of cells in G1, and a reduction of cells on interphase and G2/M in knockdown cells were seen. Furthermore, PLCδ4 knockdown increased the percentage of senescent cells, p16 INK4A+ and p21 Cip1 mRNAs expression, which could explain the impaired cell proliferation. The results show that hPLCδ4 is in involved in cellular proliferation and senescence in hASC. Copyright © 2018 Elsevier Inc. All rights reserved.

Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Yuan-Hung; Ho, Po-Chun; Chen, Min-Shan

Highlights: Black-Right-Pointing-Pointer Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. Black-Right-Pointing-Pointer Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. Black-Right-Pointing-Pointer MCE during adipogenesis is abolished in the lack of the phosphorylation. Black-Right-Pointing-Pointer Homozygous Y114F mice are resistant to high fat diet induced obesity. Black-Right-Pointing-Pointer Our results shed light on the interface between proliferation and differentiation. -- Abstract: Clonal proliferation is an obligatory component of adipogenesis. Although several cell cycle regulators are known to participate in the transition between pre-adipocyte proliferation and terminal adipocyte differentiation, how the core DNA synthesis machinery is coordinately regulated in adipogenesismore » remains elusive. PCNA (Proliferating Cell Nuclear Antigen) is an indispensable component for DNA synthesis during proliferation. Here we show that PCNA is subject to phosphorylation at the highly conserved tyrosine residue 114 (Y114). Replacing the Y114 residue with phenylalanine (Y114F), which is structurally similar to tyrosine but cannot be phosphorylated, does not affect normal animal development. However, when challenged with high fat diet, mice carrying homozygous Y114F alleles (PCNA{sup F/F}) are resistant to adipose tissue enlargement in comparison to wild-type (WT) mice. Mouse embryonic fibroblasts (MEFs) harboring WT or Y114F mutant PCNA proliferate at similar rates. However, when subjected to adipogenesis induction in culture, PCNA{sup F/F} MEFs are not able to re-enter the cell cycle and fail to form mature adipocytes, while WT MEFs undergo mitotic clonal expansion in response to the adipogenic stimulation, accompanied by enhanced Y114 phosphorylation of PCNA, and differentiate to mature adipocytes. Consistent with the function of Y114 phosphorylation in clonal proliferation in adipogenesis, fat tissues isolated

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

TODOSOW,M.; KAZIMI,M.

2004-08-01

Issues affecting the implementation, public perception and acceptance of nuclear power include: proliferation, radioactive waste, safety, and economics. The thorium cycle directly addresses the proliferation and waste issues, but optimization studies of core design and fuel management are needed to ensure that it fits within acceptable safety and economic margins. Typical pressurized water reactors, although loaded with uranium fuel, produce 225 to 275 kg of plutonium per gigawatt-year of operation. Although the spent fuel is highly radioactive, it nevertheless offers a potential proliferation pathway because the plutonium is relatively easy to separate, amounts to many critical masses, and does notmore » present any significant intrinsic barrier to weapon assembly. Uranium 233, on the other hand, produced by the irradiation of thorium, although it too can be used in weapons, may be ''denatured'' by the addition of natural, depleted or low enriched uranium. Furthermore, it appears that the chemical behavior of thoria or thoria-urania fuel makes it a more stable medium for the geological disposal of the spent fuel. It is therefore particularly well suited for a once-through fuel cycle. The use of thorium as a fertile material in nuclear fuel has been of interest since the dawn of nuclear power technology due to its abundance and to potential neutronic advantages. Early projects include homogeneous mixtures of thorium and uranium oxides in the BORAX-IV, Indian Point I, and Elk River reactors, as well as heterogeneous mixtures in the Shippingport seed-blanket reactor. However these projects were developed under considerably different circumstances than those which prevail at present. The earlier applications preceded the current proscription, for non-proliferation purposes, of the use of uranium enriched to more than 20 w/o in {sup 235}U, and has in practice generally prohibited the use of uranium highly enriched in {sup 235}U. They were designed when the expected

International training course on nuclear materials accountability for safeguards purposes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-12-01

The two volumes of this report incorporate all lectures and presentations at the International Training Course on Nuclear Materials Accountability and Control for Safeguards Purposes, held May 27-June 6, 1980, at the Bishop's Lodge near Santa Fe, New Mexico. The course, authorized by the US Nuclear Non-Proliferation Act and sponsored by the US Department of Energy in cooperation with the International Atomic Energy Agency, was developed to provide practical training in the design, implementation, and operation of a National system of nuclear materials accountability and control that satisfies both National and IAEA International safeguards objectives. Volume I, covering the firstmore » week of the course, presents the background, requirements, and general features of material accounting and control in modern safeguard systems. Volume II, covering the second week of the course, provides more detailed information on measurement methods and instruments, practical experience at power reactor and research reactor facilities, and examples of operating state systems of accountability and control.« less

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation

PubMed Central

Sun, GuoQiang; Yu, Ruth T.; Evans, Ronald M.; Shi, Yanhong

2007-01-01

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359–385, which contains a conserved nuclear receptor–coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21CIP1/WAF1(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX–HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX–HDAC interactions. PMID:17873065

The Science of Nuclear Materials: A Modular, Laboratory-based Curriculum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cahill, C.L., E-mail: cahill@gwu.edu; Feldman, G.; Briscoe, W.J.

The development of a curriculum for nuclear materials courses targeting students pursuing Master of Arts degrees at The George Washington University is described. The courses include basic concepts such as radiation and radioactivity as well as more complex topics such the nuclear fuel cycle, nuclear weapons, radiation detection and technological aspects of non-proliferation.

Non-proliferation, safeguards, and security for the fissile materials disposition program immobilization alternatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duggan, R.A.; Jaeger, C.D.; Tolk, K.M.

1996-05-01

The Department of Energy is analyzing long-term storage and disposition alternatives for surplus weapons-usable fissile materials. A number of different disposition alternatives are being considered. These include facilities for storage, conversion and stabilization of fissile materials, immobilization in glass or ceramic material, fabrication of fissile material into mixed oxide (MOX) fuel for reactors, use of reactor based technologies to convert material into spent fuel, and disposal of fissile material using geologic alternatives. This paper will focus on how the objectives of reducing security and proliferation risks are being considered, and the possible facility impacts. Some of the areas discussed inmore » this paper include: (1) domestic and international safeguards requirements, (2) non-proliferation criteria and measures, (3) the threats, and (4) potential proliferation, safeguards, and security issues and impacts on the facilities. Issues applicable to all of the possible disposition alternatives will be discussed in this paper. However, particular attention is given to the plutonium immobilization alternatives.« less

Nuclear targeting of viral and non-viral DNA.

PubMed

Chowdhury, E H

2009-07-01

The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins.

History of Nuclear India

NASA Astrophysics Data System (ADS)

Chaturvedi, Ram

2000-04-01

India emerged as a free and democratic country in 1947, and entered into the nuclear age in 1948 by establishing the Atomic Energy Commission (AEC), with Homi Bhabha as the chairman. Later on the Department of Atomic Energy (DAE) was created under the Office of the Prime Minister Jawahar Lal Nehru. Initially the AEC and DAE received international cooperation, and by 1963 India had two research reactors and four nuclear power reactors. In spite of the humiliating defeat in the border war by China in 1962 and China's nuclear testing in 1964, India continued to adhere to the peaceful uses of nuclear energy. On May 18, 1974 India performed a 15 kt Peaceful Nuclear Explosion (PNE). The western powers considered it nuclear weapons proliferation and cut off all financial and technical help, even for the production of nuclear power. However, India used existing infrastructure to build nuclear power reactors and exploded both fission and fusion devices on May 11 and 13, 1998. The international community viewed the later activity as a serious road block for the Non-Proliferation Treaty and the Comprehensive Test Ban Treaty; both deemed essential to stop the spread of nuclear weapons. India considers these treaties favoring nuclear states and is prepared to sign if genuine nuclear disarmament is included as an integral part of these treaties.

The nuclear issue: where do we go from here?.

PubMed

Rotblat, Joseph

2003-01-01

The drive for the elimination of nuclear weapons is going badly and there is currently little support from the general public. The United States Nuclear Posture Review incorporates nuclear capability into conventional war planning. The Stockpile Stewardship Program is designed to maintain nuclear weapon capability. The US is planning an essentially new earth-penetrating nuclear weapon and is prepared to test this in the national interest if thought necessary. These policies could stimulate nuclear proliferation by others, do nothing to deter terrorism, promote persisting polarization of the world, are a clear breach of the Non-Proliferation Treaty and rest world security on a continued balance of terror. A renewed mass campaign to counteract all this, on legal and moral grounds in particular, is urgently needed. IPPNW and kindred organizations must restore sanity in our policies and humanity to our actions.

Kaon Condensation and the Non-Uniform Nuclear Matter

NASA Astrophysics Data System (ADS)

Maruyama, Toshiki; Tatsumi, Toshitaka; Voskresensky, Dmitri N.; Tanigawa, Tomonori; Chiba, Satoshi

2004-04-01

Non-uniform structures of nuclear matter are studied in a wide density-range. Using the density functional theory with a relativistic mean-field model, we examine non-uniform structures at sub-nuclear densities (nuclear "pastas") and at high densities, where kaon condensate is expected. We try to give a unified view about the change of the matter structure as density increases, carefully taking into account the Coulomb screening effects from the viewpoint of first-order phase transition.

The EU and U.S. Strategies against Terrorism and Proliferation of WMD: A Comparative Study

DTIC Science & Technology

2007-01-01

attitude, which they see as simplistic. As French Foreign Minister Hubert Vedrine said in 2002, “For George W. Bush all the world’s problems come...EU’s Emerging Role in Nuclear Non-proliferation. Ed. by Marco Overhaus, Hanns W. Maull and Sebastian Harnisch, Volume 6, Newsletter No. 17, October

Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα) in a Mouse Liver Gene Expression Compendium

EPA Science Inventory

The nuclear receptor family member peroxisome proliferator-activated receptor α (PPARα) is activated by therapeutic hypolipidemic drugs and environmentally-relevant chemicals to regulate genes involved in lipid transport and catabolism. Chronic activation of PPARα in rodents inc...

Workshop on nuclear power growth and nonproliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilat, Joseph F

2010-01-01

It is widely viewed that an expansion of nuclear power would have positive energy, economic and environmental benefits for the world. However, there are concerns about the economic competitiveness, safety and proliferation and terrorism risks of nuclear power. The prospects for a dramatic growth in nuclear power will depend on the ability of governments and industry to address these concerns, including the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen nonproliferation, nuclear materials accountability and nuclear security. In his Prague speech, President Obama stated: 'we should build a new framework formore » civil nuclear cooperation, including an international fuel bank, so that countries can access peaceful power without increasing the risks of proliferation. That must be the right of every nation that renounces nuclear weapons, especially developing countries embarking on peaceful programs. And no approach will succeed if it's based on the denial of rights to nations that play by the rules. We must harness the power of nuclear energy on behalf of our efforts to combat climate change, and to advance peace opportunity for all people.' How can the President's vision, which will rekindle a vigorous public debate over the future of nuclear power and its relation to proliferation, be realized? What critical issues will frame the reemerging debate? What policies must be put into place to address these issues? Will US policy be marked more by continuity or change? To address these and other questions, the Los Alamos National Laboratory in cooperation with the Woodrow Wilson International Center for Scholars will host a workshop on the future of nuclear power and nonproliferation.« less

Worldwide Report, Nuclear Development and Proliferation

DTIC Science & Technology

1986-07-09

Union’s Nuclear Disaster ? This reporter asked Vice Minister Zhou Ping: In your opinion, how should we view the Soviet Union’s recent nuclear accident...statement on Thurs- day announced that Bangladesh environment remained free from pullution follow- ing recent nuclear disaster at Chernobyl Nuclear...Chernobyl were based largely on nuclear disaster . American practice. However, a statement Mr Semark said de- issued yesterday by Es- tailed plans

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

EPA Science Inventory

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

Technology Implementation Plan: Irradiation Testing and Qualification for Nuclear Thermal Propulsion Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrison, Thomas J.; Howard, Richard H.; Rader, Jordan D.

This document is a notional technology implementation plan (TIP) for the development, testing, and qualification of a prototypic fuel element to support design and construction of a nuclear thermal propulsion (NTP) engine, specifically its pre-flight ground test. This TIP outlines a generic methodology for the progression from non-nuclear out-of-pile (OOP) testing through nuclear in-pile (IP) testing, at operational temperatures, flows, and specific powers, of an NTP fuel element in an existing test reactor. Subsequent post-irradiation examination (PIE) will occur in existing radiological facilities. Further, the methodology is intended to be nonspecific with respect to fuel types and irradiation or examinationmore » facilities. The goals of OOP and IP testing are to provide confidence in the operational performance of fuel system concepts and provide data to program leadership for system optimization and fuel down-selection. The test methodology, parameters, collected data, and analytical results from OOP, IP, and PIE will be documented for reference by the NTP operator and the appropriate regulatory and oversight authorities. Final full-scale integrated testing would be performed separately by the reactor operator as part of the preflight ground test.« less

76 FR 36986 - Export Controls for High Performance Computers: Wassenaar Arrangement Agreement Implementation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... regimes and is working on becoming a member of the regimes. Albania and Croatia are parties to the Nuclear Non-Proliferation Treaty, the Chemical Weapons Convention, and the Biological Weapons Convention. In...

Director`s series on proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1994-10-17

This series is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. Essays contained in this document include: Key issues on NPT renewal and extension, Africa and nuclear nonproliferation, Kenya`s views on the NPT, Prospects for establishing a zone free of weapons of mass destruction in the middle east, effects of a special nuclear weapon materials cut-off convention, and The UK view of NPT renewal.

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer.

PubMed

Naryzhny, Stanislav N; Lee, Hoyun

2010-10-22

Proliferating cell nuclear antigen (PCNA) is involved in a wide range of functions in the nucleus. However, a substantial amount of PCNA is also present in the cytoplasm, although their function is unknown. Here we show, through Far-Western blotting and mass spectrometry, that PCNA is associated with several cytoplasmic oncoproteins, including elongation factor, malate dehydrogenase, and peptidyl-prolyl isomerase. Surprisingly, PCNA is also associated with six glycolytic enzymes that are involved in the regulation of steps 4-9 in the glycolysis pathway. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yongfang; Xu, Lianhong; Jiang, Lixin, E-mail: jianglx66766@163.com

2015-03-13

MicroRNAs (miRNAs) are short, non-coding RNAs (∼22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating numerous target genes at posttranscriptional level. However, the role of microRNAs in lung cancer, particularly non-small-cell lung cancer (NSCLC), has remained elusive. In this study, two microRNAs, miR-1271 and miR-628, and their predicted target genes were identified differentially expressed in NSCLC by analyzing the miRNA and mRNA expression data from NSCLC tissues and their matching normal controls. miR-1271 and its target gene HOXA5 were selected for further investigation. CCK-8 proliferation assay showed that the cell proliferation was promoted by miR-1271more » in NSCLC cells, while miR-1271 inhibitor could significantly inhibited the proliferation of NSCLC cells. Interestingly, migration and invasion assay indicated that overexpression of miR-1271 could significantly promoted the migration and invasion of NSCLC cells, whereas miR-1271 inhibitor could inhibited both cell migration and invasion of NSCLC cells. Western blot showed that miR-1271 suppressed the protein level of HOXA5, and luciferase assays confirmed that miR-1271 directly bound to the 3'untranslated region of HOXA5. This study indicated indicate that miR-1271 regulates NSCLC cell proliferation and invasion, via the down-regulation of HOXA5. Thus, miR-1271 may represent a potential therapeutic target for NSCLC intervention. - Highlights: • Overexpression of miR-1271 promoted proliferation and invasion of NSCLC cells. • miR-1271 inhibitor inhibited the proliferation and invasion of NSCLC cells. • miR-1271 targets 3′ UTR of HOXA5 in NSCLC cells. • miR-1271 negatively regulates HOXA5 in NSCLC cells.« less

Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver

PubMed Central

Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko

2014-01-01

The liver is endowed with the ability to regenerate hepatocytes in response to injury. When this regeneration ability is impaired during liver injury, oval cells, which are considered to be postnatal hepatic progenitors, proliferate and differentiate into hepatocytes. Here we have demonstrated that 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver. Activation of CAR by DDC was shown by hepatic nuclear CAR accumulation and cytochrome P450 (CYP)2B10 mRNA induction after feeding a 0.1% DDC-containing diet to Car +/+ mice. After being fed the DDC diet, Car +/+, but not Car−/− mice, developed severe liver injury and an A6 antibody-stained ductular reaction in an area around the portal tract. Oval cell proliferation was confirmed by laser capture microdissection and real-time PCR; mRNAs for the two oval cell markers epithelial cell adhesion molecule and TROP2 were specifically induced in the periportal region of DDC diet-fed Car +/+, but not Car−/− mice. Although rates of both hepatocyte growth and death were initially enhanced only in DDC diet-fed Car +/+ mice, growth was attenuated when oval cells proliferated, whereas death continued unabated. DDC-induced liver injury, which differs from other CAR activators such as phenobarbital, occurred in the periportal region where cells developed hypertrophy, accumulated porphyrin crystals and inflammation developed, all in association with the proliferation of oval cells. Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma. PMID:21826054

Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver.

PubMed

Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko

2011-11-01

The liver is endowed with the ability to regenerate hepatocytes in response to injury. When this regeneration ability is impaired during liver injury, oval cells, which are considered to be postnatal hepatic progenitors, proliferate and differentiate into hepatocytes. Here we have demonstrated that 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver. Activation of CAR by DDC was shown by hepatic nuclear CAR accumulation and cytochrome P450 (CYP)2B10 mRNA induction after feeding a 0.1% DDC-containing diet to Car(+/+) mice. After being fed the DDC diet, Car(+/+), but not Car(-/-) mice, developed severe liver injury and an A6 antibody-stained ductular reaction in an area around the portal tract. Oval cell proliferation was confirmed by laser capture microdissection and real-time PCR; mRNAs for the two oval cell markers epithelial cell adhesion molecule and TROP2 were specifically induced in the periportal region of DDC diet-fed Car(+/+), but not Car(-/-) mice. Although rates of both hepatocyte growth and death were initially enhanced only in DDC diet-fed Car(+/+) mice, growth was attenuated when oval cells proliferated, whereas death continued unabated. DDC-induced liver injury, which differs from other CAR activators such as phenobarbital, occurred in the periportal region where cells developed hypertrophy, accumulated porphyrin crystals and inflammation developed, all in association with the proliferation of oval cells. Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma.

``Recycling'' Nuclear Power Plant Waste: Technical Difficulties and Proliferation Concerns

NASA Astrophysics Data System (ADS)

Lyman, Edwin

2007-04-01

One of the most vexing problems associated with nuclear energy is the inability to find a technically and politically viable solution for the disposal of long-lived radioactive waste. The U.S. plan to develop a geologic repository for spent nuclear fuel at Yucca Mountain in Nevada is in jeopardy, as a result of managerial incompetence, political opposition and regulatory standards that may be impossible to meet. As a result, there is growing interest in technologies that are claimed to have the potential to drastically reduce the amount of waste that would require geologic burial and the length of time that the waste would require containment. A scenario for such a vision was presented in the December 2005 Scientific American. While details differ, these technologies share a common approach: they require chemical processing of spent fuel to extract plutonium and other long-lived actinide elements, which would then be ``recycled'' into fresh fuel for advanced reactors and ``transmuted'' into shorter-lived fission products. Such a scheme is the basis for the ``Global Nuclear Energy Partnership,'' a major program unveiled by the Department of Energy (DOE) in early 2006. This concept is not new, but has been studied for decades. Major obstacles include fundamental safety issues, engineering feasibility and cost. Perhaps the most important consideration in the post-9/11 era is that these technologies involve the separation of plutonium and other nuclear weapon-usable materials from highly radioactive fission products, providing opportunities for terrorists seeking to obtain nuclear weapons. While DOE claims that it will only utilize processes that do not produce ``separated plutonium,'' it has offered no evidence that such technologies would effectively deter theft. It is doubtful that DOE's scheme can be implemented without an unacceptable increase in the risk of nuclear terrorism.

Anomalies in Proposed Regulations for the Release of Redundant Material from Nuclear and Non-nuclear Industries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menon, S.

Now that increasing numbers of nuclear power stations are reaching the end of their commercially useful lives, the management of the large quantities of very low level radioactive material that arises during their decommissioning has become a major subject of discussion, with very significant economic implications. Much of this material can, in an environmentally advantageous manner, be recycled for reuse without radiological restrictions. Much larger quantities--2-3 orders of magnitude larger--of material, radiologically similar to the candidate material for recycling from the nuclear industry, arise in non-nuclear industries like coal, fertilizer, oil and gas, mining, etc. In such industries, naturally occurringmore » radioactivity is artificially concentrated in products, by-products or waste to form TENORM (Technologically Enhanced Naturally Occurring Radioactive Material). It is only in the last decade that the international community has become aware of the prevalence of T ENORM, specially the activity levels and quantities arising in so many nonnuclear industries. The first reaction of international organizations seems to have been to propose ''double'' standards for the nuclear and non-nuclear industries, with very stringent release criteria for radioactive material from the regulated nuclear industry and up to a hundred times more liberal criteria for the release/exemption of TENORM from the as yet unregulated non-nuclear industries. There are, however, many significant strategic issues that need to be discussed and resolved. An interesting development, for both the nuclear and non-nuclear industries, is the increased scientific scrutiny that the populations of naturally high background dose level areas of the world are being subject to. Preliminary biological studies have indicated that the inhabitants of such areas, exposed to many times the permitted occupational doses for nuclear workers, have not shown any differences in cancer mortality, life

High Fidelity, Fuel-Like Thermal Simulators for Non-Nuclear Testing: Analysis and Initial Test Results

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Dickens, Ricky; Dixon, David; Kapernick, Richard

2007-01-01

Non-nuclear testing can be a valuable tool in the development of a space nuclear power system, providing system characterization data and allowing one to work through various fabrication, assembly and integration issues without the cost and time associated with a full ground nuclear test. In a non-nuclear test bed, electric heaters are used to simulate the heat from nuclear fuel. Testing with non-optimized heater elements allows one to assess thermal, heat transfer. and stress related attributes of a given system, but fails to demonstrate the dynamic response that would be present in an integrated, fueled reactor system. High fidelity thermal simulators that match both the static and the dynamic fuel pin performance that would be observed in an operating, fueled nuclear reactor can vastly increase the value of non-nuclear test results. With optimized simulators, the integration of thermal hydraulic hardware tests with simulated neutronic response provides a bridge between electrically heated testing and fueled nuclear testing. By implementing a neutronic response model to simulate the dynamic response that would be expected in a fueled reactor system, one can better understand system integration issues, characterize integrated system response times and response characteristics and assess potential design improvements at relatively small fiscal investment. Initial conceptual thermal simulator designs are determined by simple one-dimensional analysis at a single axial location and at steady state conditions; feasible concepts are then input into a detailed three-dimensional model for comparison to expected fuel pin performance. Static and dynamic fuel pin performance for a proposed reactor design is determined using SINDA/FLUINT thermal analysis software, and comparison is made between the expected nuclear performance and the performance of conceptual thermal simulator designs. Through a series of iterative analyses, a conceptual high fidelity design is developed

Development of undergraduate nuclear security curriculum at College of Engineering, Universiti Tenaga Nasional

NASA Astrophysics Data System (ADS)

Hamid, Nasri A.; Mujaini, Madihah; Mohamed, Abdul Aziz

2017-01-01

The Center for Nuclear Energy (CNE), College of Engineering, Universiti Tenaga Nasional (UNITEN) has a great responsibility to undertake educational activities that promote developing human capital in the area of nuclear engineering and technology. Developing human capital in nuclear through education programs is necessary to support the implementation of nuclear power projects in Malaysia in the near future. In addition, the educational program must also meet the nuclear power industry needs and requirements. In developing a certain curriculum, the contents must comply with the university's Outcomes Based Education (OBE) philosophy. One of the important courses in the nuclear curriculum is in the area of nuclear security. Basically the nuclear security course covers the current issues of law, politics, military strategy, and technology with regard to weapons of mass destruction and related topics in international security, and review legal regulations and political relationship that determine the state of nuclear security at the moment. In addition, the course looks into all aspects of the nuclear safeguards, builds basic knowledge and understanding of nuclear non-proliferation, nuclear forensics and nuclear safeguards in general. The course also discusses tools used to combat nuclear proliferation such as treaties, institutions, multilateral arrangements and technology controls. In this paper, we elaborate the development of undergraduate nuclear security course at the College of Engineering, Universiti Tenaga Nasional. Since the course is categorized as mechanical engineering subject, it must be developed in tandem with the program educational objectives (PEO) of the Bachelor of Mechanical Engineering program. The course outcomes (CO) and transferrable skills are also identified. Furthermore, in aligning the CO with program outcomes (PO), the PO elements need to be emphasized through the CO-PO mapping. As such, all assessments and distribution of Bloom Taxonomy

Structure and biochemical characterization of proliferating cellular nuclear antigen from a parasitic protozoon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardona-Felix, Cesar S.; Lara-Gonzalez, Samuel; Brieba, Luis G.

2012-02-08

Proliferating cellular nuclear antigen (PCNA) is a toroidal-shaped protein that is involved in cell-cycle control, DNA replication and DNA repair. Parasitic protozoa are early-diverged eukaryotes that are responsible for neglected diseases. In this work, a PCNA from a parasitic protozoon was identified, cloned and biochemically characterized and its crystal structure was determined. Structural and biochemical studies demonstrate that PCNA from Entamoeba histolytica assembles as a homotrimer that is able to interact with and stimulate the activity of a PCNA-interacting peptide-motif protein from E. histolytica, EhDNAligI. The data indicate a conservation of the biochemical mechanisms of PCNA-mediated interactions between metazoa, yeastmore » and parasitic protozoa.« less

Blocking the spread of nuclear weapons. American and European perspectives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, G.C.; Holst, J.J.

1986-01-01

This volume is the product of separate but parallel studies undertaken by two panels of experts-one from the United States, the other from Western Europe-on new approaches to preventing the proliferation of nuclear weapons to additional countries. Neither panel sounded a doomsday alarm; each concluded that the chances for controlling proliferation lie in good part on building on the sound foundation of existing policies and institutional structures. Among the other conclusions derived from the parallel studies: The threat of nuclear proliferation is a specific, definable danger in a limited number of countries. The incentives that appear to make nuclear weaponsmore » an interesting option to some states must be understood, and potential proliferators must be persuaded that their acquisition will not lead to national security. Effective persuasion is more likely to come from non-nuclear weapon nations. Europe and the United States must collaborate in engaging such third-party persuaders in this endeavor. The panels' intensive examination of the six states of greatest near-term concern leads to the conclusion that the uneasy status quo will probably prevail for the next several years, yet these are volatile situations. The nature of the threat demands an extraordinary degree of international collaboration.« less

Implementing the correlated fermi gas nuclear model for quasielastic neutrino-nucleus scattering

NASA Astrophysics Data System (ADS)

Tockstein, Jameson

2017-09-01

When studying neutrino oscillations an understanding of charged current quasielastic (CCQE) neutrino-nucleus scattering is imperative. This interaction depends on a nuclear model as well as knowledge of form factors. Neutrino experiments, such as MiniBooNE, often use the Relativistic Fermi Gas (RFG) nuclear model. Recently, the Correlated Fermi Gas (CFG) nuclear model was suggested in, based on inclusive and exclusive scattering experiments at JLab. We implement the CFG model for CCQE scattering. In particular, we provide analytic expressions for this implementation that can be used to analyze current and future neutrino CCQE data. This project was supported through the Wayne State University REU program under NSF Grant PHY-1460853 and by the DOE Grant DE-SC0007983.

Nuclear obligations: Nuremberg law, nuclear weapons, and protest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burroughs, J.R.

1991-01-01

Nuclear weapons use and deployment and nonviolent anti-nuclear protests are evaluated. Use of nuclear weapons would constitute war crimes and crimes against humanity as defined in both the Nuremberg Charter and Allied Control Council Law No. 10 and applied by the International Military Tribunal and other Nuremberg courts. Strategic and atomic bombing during World War 2 did not set a precedent for use of nuclear weapons. The consequentialist argument for World War 2 bombing fails and the bombing has also been repudiated by codification of the law of war in Protocol 1 to the 1949 Geneva Conventions. The legality ofmore » deploying nuclear weapons as instruments of geopolitical policy is questionable when measured against the Nuremberg proscription of planning and preparation of aggressive war, war crimes, and crimes against humanity and the United Nations Charter's proscription of aggressive threat of force. While states' practice of deploying the weapons and the arms-control treaties that regulate but do not prohibit mere possession provide some support for legality, those treaties recognize the imperative of preventing nuclear war, and the Nuclear Non-Proliferation Treaty commits nuclear-armed states to good-faith negotiation of nuclear disarmament.« less

Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

PubMed Central

Sáez, María E; Grilo, Antonio; Morón, Francisco J; Manzano, Luis; Martínez-Larrad, María T; González-Pérez, Antonio; Serrano-Hernando, Javier; Ruiz, Agustín; Ramírez-Lorca, Reposo; Serrano-Ríos, Manuel

2008-01-01

Context Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. PMID:18657264

Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Byeong-Moo; Department of Medicine, Harvard Medical School, Boston, MA 02115; Choi, Michael Y., E-mail: mchoi@partners.org

2012-09-21

Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generatemore » mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.« less

The nuclear present. A guide to recent books on nuclear war, weapons, the peace movement, and related issues, with a chronology of nuclear events, 1789-1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burns, G.

The Nuclear Present brings the interested reader up-to-date on significant English-language books about nuclear weapons and related topics, identifying primarily important works of nuclear non-fiction that have come out since 1984. Each reference has a paragraph of comment about its subject and value. General organizational areas include the following: Reference Works; Nuclear weapons and Nuclear war (14 sub-headings including overviews, development, effects, tests, arms race, prospectives, legal considerations etc.); Strategy; proliferation; Stratigic Defense; Arms control and disarmament; ethical, pholosophical and religous perspectives; new paths to peace; periodic guide; the Chernobyl Disaster. An extensive Nuclear Chronology (1789-1991) written by the authormore » allows a fairly detailed sense of the historical record of nuclear weapons, including testing, manufacture, use and movements for arms control and disarmament.« less

Low power laser irradiation stimulates cell proliferation via proliferating cell nuclear antigen and Ki-67 expression during tissue repair

NASA Astrophysics Data System (ADS)

Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Mahato, Krishna Kishore

2015-03-01

Low power laser irradiation (LPLI) is becoming an increasingly popular and fast growing therapeutic modality in dermatology to treat various ailments without any reported side effects. In the present study an attempt was made to investigate the proliferative potential of red laser light during tissue repair in Swiss albino mice. To this end, full thickness excisional wounds of diameter 15 mm created on mice were exposed to single dose of Helium-Neon laser (632.8 nm; 7 mW; 4.02 mWcm-2; Linear polarization) at 2 Jcm-2 and 10 Jcm-2 along with un-illuminated controls. The granulation tissues from all the respective experimental groups were harvested on day 10 post-wounding following euthanization. Subsequently, tissue regeneration potential of these laser doses under study were evaluated by monitoring proliferating cell nuclear antigen and Ki-67 following the laser treatment and comparing it with the un-illuminated controls. The percentages of Ki-67 or PCNA positive cells were determined by counting positive nuclei (Ki-67/PCNA) and total nuclei in five random fields per tissue sections. Animal wounds treated with single exposure of the 2 Jcm-2 indicated significant elevation in PCNA (P<0.01) and Ki-67 (P<0.05 compared to un-illuminated control and P<0.01 compared to 10 Jcm-2) expression as compared to other tested experimental groups as evidenced by the microscopy results in the study. In summary, the findings of the present study have clearly demonstrated the regulation of cell proliferation by LPLI via PCNA and Ki-67 expression during tissue regeneration.

Hypoxia induces pulmonary fibroblast proliferation through NFAT signaling.

PubMed

Senavirathna, Lakmini Kumari; Huang, Chaoqun; Yang, Xiaoyun; Munteanu, Maria Cristina; Sathiaseelan, Roshini; Xu, Dao; Henke, Craig A; Liu, Lin

2018-02-09

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation. Hypoxia increased the proliferation of normal human pulmonary fibroblasts and IPF fibroblasts after exposure for 3-6 days. Cell cycle analysis demonstrated that hypoxia promoted the G1/S phase transition. Hypoxia downregulated cyclin D1 and A2 levels, while it upregulated cyclin E1 protein levels. However, hypoxia had no effect on the protein expression levels of cyclin-dependent kinase 2, 4, and 6. Chemical inhibition of hypoxia-inducible factor (HIF)-2 reduced hypoxia-induced fibroblast proliferation. Moreover, silencing of Nuclear Factor Activated T cell (NFAT) c2 attenuated the hypoxia-mediated fibroblasts proliferation. Hypoxia also induced the nuclear translocation of NFATc2, as determined by immunofluorescence staining. NFAT reporter assays showed that hypoxia-induced NFAT signaling activation is dependent on HIF-2, but not HIF-1. Furthermore, the inhibition or silencing of HIF-2, but not HIF-1, reduced the hypoxia-mediated NFATc2 nuclear translocation. Our studies suggest that hypoxia induces the proliferation of human pulmonary fibroblasts through NFAT signaling and HIF-2.

Nuclear Factor I-C promotes proliferation and differentiation of apical papilla-derived human stem cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jing; Stomatologic Hospital & College, Anhui Medical University, Key Lab of Oral Diseases Research of Anhui Province, Hefei; Wang, Zhihua

The transcription factor Nuclear Factor I-C (NFIC) has been implicated in the regulation of tooth root development, where it may be anticipated to impact on the behavior of stem cells from the apical papilla (SCAPs) and root odontoblast activity. We hypothesized that NFIC may provide an important target for promoting dentin/root regeneration. In the present study, the effects of NFIC on the proliferation and differentiation of SCAPs were investigated. Over-expression of NFIC increased cell proliferation, mineralization nodule formation and alkaline phosphatase (ALP) activity in SCAPs. Furthermore, NFIC up-regulated the mRNA levels of odontogenic-related markers, ALP, osteocalcin and collagen type Imore » as well as dentin sialoprotein protein levels. In contrast, knockdown of NFIC by si-RNA inhibited the mineralization capacity of SCAPs and down-regulated the expression of odontogenic-related markers. In conclusion, the results indicated that upregulation of NFIC activity in SCAPs may promote osteo/odontoblastic differentiation of SCAPs. - Highlights: • NFIC promotes the proliferation of SCAPs in vitro. • NFIC promotes osteo/odontogenic differentiation of SCAPs in vitro. • Knockdown of NFIC inhibits odontogenic differentiation in SCAPs.« less

Worldwide Report, Nuclear Development and Proliferation

DTIC Science & Technology

1984-05-14

PROLIFERATION IMC QUALITY: 19980729 081 FBIS FOREIGN BROADCAST INFORMATION SERVICE REPRODUCED BY NATIONAL TECHNICAL INFORMATION SERVICE U.S...Information Service , Springfield, Virginia 22161. In order- ing, it is recommended that the JPRS number, title, date and author, if applicable, of...Information Service , and are listed in the Monthly Catalog of U.S. Government Publications issued by the Superintendent of Documents, U.S. Government

International academic program in technologies of light-water nuclear reactors. Phases of development and implementation

NASA Astrophysics Data System (ADS)

Geraskin, N. I.; Glebov, V. B.

2017-01-01

The results of implementation of European educational projects CORONA and CORONA II dedicated to preserving and further developing nuclear knowledge and competencies in the area of technologies of light-water nuclear reactors are analyzed. Present article addresses issues of design and implementation of the program for specialized training in the branch of technologies of light-water nuclear reactors. The systematic approach has been used to construct the program for students of nuclear specialties, which corresponding to IAEA standards and commonly accepted nuclear principles recognized in the European Union. Possibilities of further development of the international cooperation between countries and educational institutions are analyzed. Special attention is paid to e-learning/distance training, nuclear knowledge preservation and interaction with European Nuclear Education Network.

CVX: Propulsion System Decision. Industrial Base Implications of Nuclear and Non-Nuclear Options

DTIC Science & Technology

1998-01-01

industrial base may be affected by the demand for either a nuclear or non-nuclear CVX. If CVX were conventional, the cost of components for other...air- craft carrier, designated CVX. Because of the high cost of designing a new carrier and because of competing demands within its budget, the Navy...reactor re- fuelings. The organizations also supplied workforce requirements associated with different nuclear workload demands and the costs of

Review of non-nuclear density gauges as possible replacements for ITD's nuclear density gauges.

DOT National Transportation Integrated Search

2015-01-01

This report examines the possibility of replacing nuclear density gauges (NDGs) with non-nuclear density gauges (NNDGs) to : measure density of hot mix asphalt (HMA) and unbound pavement layers in the field. The research team evaluated the : effectiv...

Analysis of the Heat Shock Response in Mouse Liver Reveals Transcriptional Dependence on the Nuclear Receptor Peroxisome Proliferator-Activated Receptor alpha (PPARα)

EPA Science Inventory

BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by h...

Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

PubMed Central

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

PubMed

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

Iran and Iraq - the proliferation challenge. Strategic research report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jordan, F.R.

1996-04-15

Worldwide proliferation of weapons of mass destruction and ballistic missiles has been on the rise since the end of the Cold War. This escalation has brought a new set of challenges to post-Cold War strategists and policymakers. This study focus on the impact of nuclear proliferation in the Middle East. It assesses the possibility of Iran`s and Iraq`s ability to develop a nuclear capability within the next twenty to thirty years. United States` strategy and policy to counter this potential is also considered.

An Overview of the Regulation of Low Dose Radiation in the Nuclear and Non-nuclear Industries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menon, Shankar; Valencia, Luis; Teunckens, Lucien

Now that increasing numbers of nuclear power stations are reaching the end of their commercially useful lives, the management of the large quantities of very low level radioactive material that arises during their decommissioning has become a major subject of discussion, with very significant economic implications. Much of this material can, in an environmentally advantageous manner, be recycled for reuse without radiological restrictions. Much larger quantities--2-3 orders of magnitude larger--of material, radiologically similar to the candidate material for recycling from the nuclear industry, arise in non-nuclear industries like coal, fertilizer, oil and gas, mining, etc. In such industries, naturally occurringmore » radioactivity is artificially concentrated in products, by-products or waste to form TENORM (Technologically Enhanced Naturally Occurring Radioactive Material). It is only in the last decade that the international community has become aware of the prevalence of TENORM, specially the activity levels and quantities arising in so many non-nuclear industries. The first reaction of international organizations seems to have been to propose different standards for the nuclear and non-nuclear industries, with very stringent release criteria for radioactive material from the regulated nuclear industry and up to thirty to a hundred times more liberal criteria for the release/exemption of TENORM from the as yet unregulated non-nuclear industries. There are significant strategic issues that need to be discussed and resolved. Some examples of these are: - Disposal aspects of long-lived nuclides, - The use of radioactive residues in building materials, - Commercial aspects of differing and discriminating criteria in competing power industries in a world of deregulated electric power production. Of even greater importance is the need for the discussion of certain basic issues, such as - The quantitative risk levels of exposure to ionizing radiation, - The need

A simple non-perturbing cell migration assay insensitive to proliferation effects.

PubMed

Glenn, Honor L; Messner, Jacob; Meldrum, Deirdre R

2016-08-18

Migration is a fundamental cellular behavior that plays an indispensable role in development and homeostasis, but can also contribute to pathology such as cancer metastasis. Due to its relevance to many aspects of human health, the ability to accurately measure cell migration is of broad interest, and numerous approaches have been developed. One of the most commonly employed approaches, because of its simplicity and throughput, is the exclusion zone assay in which cells are allowed to migrate into an initially cell-free region. A major drawback of this assay is that it relies on simply counting cells in the exclusion zone and therefore cannot distinguish the effects of proliferation from migration. We report here a simple modification to the exclusion zone migration assay that exclusively measures cell migration and is not affected by proliferation. This approach makes use of a lineage-tracing vital stain that is retained through cell generations and effectively reads out migration relative to the original, parental cell population. This modification is simple, robust, non-perturbing, and inexpensive. We validate the method in a panel of cell lines under conditions that inhibit or promote migration and demonstrate its use in normal and cancer cell lines as well as primary cells.

A simple non-perturbing cell migration assay insensitive to proliferation effects

PubMed Central

Glenn, Honor L.; Messner, Jacob; Meldrum, Deirdre R.

2016-01-01

Migration is a fundamental cellular behavior that plays an indispensable role in development and homeostasis, but can also contribute to pathology such as cancer metastasis. Due to its relevance to many aspects of human health, the ability to accurately measure cell migration is of broad interest, and numerous approaches have been developed. One of the most commonly employed approaches, because of its simplicity and throughput, is the exclusion zone assay in which cells are allowed to migrate into an initially cell-free region. A major drawback of this assay is that it relies on simply counting cells in the exclusion zone and therefore cannot distinguish the effects of proliferation from migration. We report here a simple modification to the exclusion zone migration assay that exclusively measures cell migration and is not affected by proliferation. This approach makes use of a lineage-tracing vital stain that is retained through cell generations and effectively reads out migration relative to the original, parental cell population. This modification is simple, robust, non-perturbing, and inexpensive. We validate the method in a panel of cell lines under conditions that inhibit or promote migration and demonstrate its use in normal and cancer cell lines as well as primary cells. PMID:27535324

E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells.

PubMed

Park, Song Yi; Shin, Jee-Hye; Kee, Sun-Ho

2017-09-01

β-Catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell-cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of malignant tumors. To explore the role of E-cadherin, we established an E-cadherin-expressing cell line, EC96, from AGS cells that featured undetectable E-cadherin expression and a high level of Wnt signaling. In EC96 cells, E-cadherin re-expression enhanced cell proliferation, although Wnt signaling activity was reduced. Subsequent analysis revealed that nuclear factor-κB (NF-κB) activation and consequent c-myc expression might be involved in E-cadherin expression-mediated cell proliferation. To facilitate rapid proliferation, EC96 cells enhance glucose uptake and produce ATP using both mitochondria oxidative phosphorylation and glycolysis, whereas AGS cells use these mechanisms less efficiently. These events appeared to be mediated by NF-κB activation. Therefore, E-cadherin re-expression and subsequent induction of NF-κB signaling likely enhance energy production and cell proliferation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Nuclear energy and security

DOE Office of Scientific and Technical Information (OSTI.GOV)

BLEJWAS,THOMAS E.; SANDERS,THOMAS L.; EAGAN,ROBERT J.

2000-01-01

Nuclear power is an important and, the authors believe, essential component of a secure nuclear future. Although nuclear fuel cycles create materials that have some potential for use in nuclear weapons, with appropriate fuel cycles, nuclear power could reduce rather than increase real proliferation risk worldwide. Future fuel cycles could be designed to avoid plutonium production, generate minimal amounts of plutonium in proliferation-resistant amounts or configurations, and/or transparently and efficiently consume plutonium already created. Furthermore, a strong and viable US nuclear infrastructure, of which nuclear power is a large element, is essential if the US is to maintain a leadershipmore » or even participatory role in defining the global nuclear infrastructure and controlling the proliferation of nuclear weapons. By focusing on new fuel cycles and new reactor technologies, it is possible to advantageously burn and reduce nuclear materials that could be used for nuclear weapons rather than increase and/or dispose of these materials. Thus, the authors suggest that planners for a secure nuclear future use technology to design an ideal future. In this future, nuclear power creates large amounts of virtually atmospherically clean energy while significantly lowering the threat of proliferation through the thoughtful use, physical security, and agreed-upon transparency of nuclear materials. The authors must develop options for policy makers that bring them as close as practical to this ideal. Just as Atoms for Peace became the ideal for the first nuclear century, they see a potential nuclear future that contributes significantly to power for peace and prosperity.« less

The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation in part by controlling proliferation and apoptosis.

PubMed

Famili, Farbod; Perez, Laura Garcia; Naber, Brigitta Ae; Noordermeer, Jasprina N; Fradkin, Lee G; Staal, Frank Jt

2016-11-24

The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. We show that there are dynamic changes in Ryk expression during development and in different hematopoietic tissues. Functionally, Ryk regulates NK cell development in a temporal fashion. Moreover, Ryk-deficient mice show diminished, but not absent self-renewal of hematopoietic stem cells (HSC), via effects on mildly increased proliferation and apoptosis. Thus, Ryk deficiency in HSCs from fetal liver reduces their quiescence, leading to proliferation-induced apoptosis and decreased self-renewal.

DOE-NE Proliferation and Terrorism Risk Assessment: FY12 Plans Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadasivan, Pratap

2012-06-21

This presentation provides background information on FY12 plans for the DOE Office of Nuclear Energy Proliferation and Terrorism Risk Assessment program. Program plans, organization, and individual project elements are described. Research objectives are: (1) Develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of current reactors; (2) Develop improvements in the affordability of new reactors to enable nuclear energy; (3) Develop Sustainable Nuclear Fuel Cycles; and (4) Understand and minimize the risks of nuclear proliferation and terrorism - Goal is to enable the use of risk information to inform NE R&D programmore » planning.« less

Approach to proliferation risk assessment based on multiple objective analysis framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrianov, A.; Kuptsov, I.; Studgorodok 1, Obninsk, Kaluga region, 249030

2013-07-01

The approach to the assessment of proliferation risk using the methods of multi-criteria decision making and multi-objective optimization is presented. The approach allows the taking into account of the specifics features of the national nuclear infrastructure, and possible proliferation strategies (motivations, intentions, and capabilities). 3 examples of applying the approach are shown. First, the approach has been used to evaluate the attractiveness of HEU (high enriched uranium)production scenarios at a clandestine enrichment facility using centrifuge enrichment technology. Secondly, the approach has been applied to assess the attractiveness of scenarios for undeclared production of plutonium or HEU by theft of materialsmore » circulating in nuclear fuel cycle facilities and thermal reactors. Thirdly, the approach has been used to perform a comparative analysis of the structures of developing nuclear power systems based on different types of nuclear fuel cycles, the analysis being based on indicators of proliferation risk.« less

Cold thyroid nodules show a marked increase in proliferation markers.

PubMed

Krohn, Knut; Stricker, Ingo; Emmrich, Peter; Paschke, Ralf

2003-06-01

Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

The ZO-1–associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density

PubMed Central

Balda, Maria S.; Garrett, Michelle D.; Matter, Karl

2003-01-01

Epithelial tight junctions regulate paracellular permeability, restrict apical/basolateral intramembrane diffusion of lipids, and have been proposed to participate in the control of epithelial cell proliferation and differentiation. Previously, we have identified ZO-1–associated nucleic acid binding proteins (ZONAB), a Y-box transcription factor whose nuclear localization and transcriptional activity is regulated by the tight junction–associated candidate tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an antisense approach or by RNA interference strongly reduced proliferation of MDCK cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced proliferation as well as nuclear ZONAB pools, indicating that promotion of proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB resulted in increased cell density in mature monolayers, and depletion of ZONAB or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate epithelial cell proliferation and cell density via a ZONAB/ZO-1–based pathway. Although this regulatory process may also involve regulation of transcription by ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence proliferation is by regulating the nuclear accumulation of CDK4. PMID:12566432

The Long Non-Coding RNA MIR503HG Enhances Proliferation of Human ALK-Negative Anaplastic Large-Cell Lymphoma.

PubMed

Huang, Po-Shuan; Chung, I-Hsiao; Lin, Yang-Hsiang; Lin, Tzu-Kang; Chen, Wei-Jan; Lin, Kwang-Huei

2018-05-14

Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma. Currently, only a few gene rearrangements have been linked to ALK-negative ALCL progression. However, the specific molecular mechanisms underlying the growth of ALK-negative ALCL tumors remain unclear. Here, we investigated aberrantly expressed, long non-coding RNAs (lncRNAs) in ALK-negative ALCL and assessed their potential biological function. MIR503HG ( miR-503 host gene) was highly expressed in ALK-negative cell lines and was significantly upregulated in tumors in mice formed from ALK-negative ALCL cell lines. Depletion of MIR503HG suppressed tumor cell proliferation in vivo and in vitro; conversely, its overexpression enhanced tumor cell growth. MIR503HG -induced proliferation was mediated by the induction of microRNA-503 ( miR - 503 ) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-β receptor (TGFBR) and enhanced tumor cell growth. Collectively, these findings support a potential role for MIR503HG in cancer cell proliferation through the miR-503 /Smurf2/TGFBR axis and indicate that MIR503HG is a potential marker in ALK-negative ALCL.

Proliferating cell nuclear antigen (Pcna) as a direct downstream target gene of Hoxc8

DOE Office of Scientific and Technical Information (OSTI.GOV)

Min, Hyehyun; Lee, Ji-Yeon; Bok, Jinwoong

2010-02-19

Hoxc8 is a member of Hox family transcription factors that play crucial roles in spatiotemporal body patterning during embryogenesis. Hox proteins contain a conserved 61 amino acid homeodomain, which is responsible for recognition and binding of the proteins onto Hox-specific DNA binding motifs and regulates expression of their target genes. Previously, using proteome analysis, we identified Proliferating cell nuclear antigen (Pcna) as one of the putative target genes of Hoxc8. Here, we asked whether Hoxc8 regulates Pcna expression by directly binding to the regulatory sequence of Pcna. In mouse embryos at embryonic day 11.5, the expression pattern of Pcna wasmore » similar to that of Hoxc8 along the anteroposterior body axis. Moreover, Pcna transcript levels as well as cell proliferation rate were increased by overexpression of Hoxc8 in C3H10T1/2 mouse embryonic fibroblast cells. Characterization of 2.3 kb genomic sequence upstream of Pcna coding region revealed that the upstream sequence contains several Hox core binding sequences and one Hox-Pbx binding sequence. Direct binding of Hoxc8 proteins to the Pcna regulatory sequence was verified by chromatin immunoprecipitation assay. Taken together, our data suggest that Pcna is a direct downstream target of Hoxc8.« less

Nuclear forensics of a non-traditional sample: Neptunium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doyle, Jamie L.; Schwartz, Daniel; Tandon, Lav

Recent nuclear forensics cases have focused primarily on plutonium (Pu) and uranium (U) materials. By definition however, nuclear forensics can apply to any diverted nuclear material. This includes neptunium (Np), an internationally safeguarded material like Pu and U, that could offer a nuclear security concern if significant quantities were found outside of regulatory control. This case study couples scanning electron microscopy (SEM) with quantitative analysis using newly developed specialized software, to evaluate a non-traditional nuclear forensic sample of Np. Here, the results of the morphological analyses were compared with another Np sample of known pedigree, as well as other traditionalmore » actinide materials in order to determine potential processing and point-of-origin.« less

Nuclear forensics of a non-traditional sample: Neptunium

DOE PAGES

Doyle, Jamie L.; Schwartz, Daniel; Tandon, Lav

2016-05-16

Recent nuclear forensics cases have focused primarily on plutonium (Pu) and uranium (U) materials. By definition however, nuclear forensics can apply to any diverted nuclear material. This includes neptunium (Np), an internationally safeguarded material like Pu and U, that could offer a nuclear security concern if significant quantities were found outside of regulatory control. This case study couples scanning electron microscopy (SEM) with quantitative analysis using newly developed specialized software, to evaluate a non-traditional nuclear forensic sample of Np. Here, the results of the morphological analyses were compared with another Np sample of known pedigree, as well as other traditionalmore » actinide materials in order to determine potential processing and point-of-origin.« less

TC-1 Overexpression Promotes Cell Proliferation in Human Non-Small Cell Lung Cancer that Can Be Inhibited by PD173074

PubMed Central

Zhang, Na; Bai, Guangzhen; Zhong, Daixing; Su, Kai; Liu, Boya; Li, Xiaofei; Wang, Yunjie; Wang, Xiaoping

2014-01-01

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC. PMID:24941347

Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

PubMed

Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

2016-01-01

Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

Decoding the function of nuclear long non-coding RNAs.

PubMed

Chen, Ling-Ling; Carmichael, Gordon G

2010-06-01

Long non-coding RNAs (lncRNAs) are mRNA-like, non-protein-coding RNAs that are pervasively transcribed throughout eukaryotic genomes. Rather than silently accumulating in the nucleus, many of these are now known or suspected to play important roles in nuclear architecture or in the regulation of gene expression. In this review, we highlight some recent progress in how lncRNAs regulate these important nuclear processes at the molecular level. Copyright 2010 Elsevier Ltd. All rights reserved.

Supporting Technology for Chain of Custody of Nuclear Weapons and Materials throughout the Dismantlement and Disposition Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bunch, Kyle J.; Jones, Anthony M.; Ramuhalli, Pradeep

The ratification and ongoing implementation of the New START Treaty have been widely regarded as noteworthy global security achievements for both the Obama Administration and the Putin (formerly Medvedev) regime. But deeper cuts that move beyond the United States and Russia to engage the P-5 and other nuclear weapons possessor states are envisioned under future arms control regimes, and are indeed required for the P-5 in accordance with their Article VI disarmament obligations in the Nuclear Non-Proliferation Treaty. Future verification needs will include monitoring the cessation of production of new fissile material for weapons, monitoring storage of warhead components andmore » fissile materials and verifying dismantlement of warheads, pits, secondary stages, and other materials. A fundamental challenge to implementing a nuclear disarmament regime is the ability to thwart unauthorized material diversion throughout the dismantlement and disposition process through strong chain of custody implementation. Verifying the declared presence, or absence, of nuclear materials and weapons components throughout the dismantlement and disposition lifecycle is a critical aspect of the disarmament process. From both the diplomatic and technical perspectives, verification under these future arms control regimes will require new solutions. Since any acceptable verification technology must protect sensitive design information and attributes to prevent the release of classified or other proliferation-sensitive information, non-nuclear non-sensitive modalities may provide significant new verification tools which do not require the use of additional information barriers. Alternative verification technologies based upon electromagnetic and acoustics could potentially play an important role in fulfilling the challenging requirements of future verification regimes. For example, researchers at the Pacific Northwest National Laboratory (PNNL) have demonstrated that low frequency

GPR30, the Non-Classical Membrane G Protein Related Estrogen Receptor, Is Overexpressed in Human Seminoma and Promotes Seminoma Cell Proliferation

PubMed Central

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Background Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. Results We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. Conclusion These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas. PMID

GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.

PubMed

Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

2012-01-01

Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.

Detection of proliferating cell nuclear antigens and interleukin-2 beta receptor molecules on mitogen- and antigen-stimulated lymphocytes.

PubMed Central

Hesketh, J; Dobbelaere, D; Griffin, J F; Buchan, G

1993-01-01

The expression of interleukin-2 receptors (IL-2R) and proliferating cell nuclear antigens (PCNA) were compared for their usefulness as markers of lymphocyte activation. Heterologous polyclonal (anti-bovine IL-2R) and monoclonal (anti-human PCNA) antibodies were used to detect the expression of these molecules on activated deer lymphocytes. Both molecules were co-expressed on blast cells which had been activated with mitogen [concanavalin A (Con A)]. There was detectable up-regulation of IL-2R expression in response to antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] stimulation while PCNA expression mimicked lymphocyte transformation (LT) reactivity. PCNA expression was found to more accurately reflect both antigen- and mitogen-activated lymphocyte activation, as estimated by LT activity. The expression of PCNA was used to identify antigen reactive cells from animals exposed to M. bovis. A very low percentage (1.1 +/- 0.4%) of peripheral blood lymphocytes from non-infected animals could be stimulated to express PCNA by in vitro culture with antigen (PPD). Within the infected group both diseased and healthy, 'in-contact', animals expressed significantly higher levels of PCNA upon antigen stimulation. PMID:8104884

Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

PubMed Central

Colombo, María Isabel; García Véscovi, Eleonora

2011-01-01

Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell. PMID:21901159

Extra-Territorial Siting of Nuclear Installations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shea, Thomas E.; Morris, Frederic A.

2009-10-07

Arrangements might be created for siting nuclear installations on land ceded by a host State for administration by an international or multinational organization. Such arrangements might prove useful in terms of resolving suspicions of proliferation in troubled areas of the world, or as a means to introduce nuclear activities into areas where political, financial or technical capabilities might otherwise make such activities unsound, or as a means to enable global solutions to be instituted for major nuclear concerns (e.g., spent fuel management). The paper examines practical matters associated with the legal and programmatic aspects of siting nuclear installations, including diplomatic/politicalmore » frameworks, engaging competent industrial bodies, protection against seizure, regulation to ensure safety and security, waste management, and conditions related to the dissolution of the extra-territorial provisions as may be agreed as the host State(s) achieve the capabilities to own and operate the installations. The paper considers the potential for using such a mechanism across the spectrum of nuclear power activities, from mining to geological repositories for nuclear waste. The paper considers the non-proliferation dimensions associated with such arrangements, and the pros and cons affecting potential host States, technology vendor States, regional neighbors and the international community. It considers in brief potential applications in several locations today.« less

FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth

PubMed Central

Karuppaiah, Kannan; Yu, Kai; Lim, Joohyun; Chen, Jianquan; Smith, Craig; Long, Fanxin

2016-01-01

ABSTRACT Fibroblast growth factor (FGF) signaling is important for skeletal development; however, cell-specific functions, redundancy and feedback mechanisms regulating bone growth are poorly understood. FGF receptors 1 and 2 (Fgfr1 and Fgfr2) are both expressed in the osteoprogenitor lineage. Double conditional knockout mice, in which both receptors were inactivated using an osteoprogenitor-specific Cre driver, appeared normal at birth; however, these mice showed severe postnatal growth defects that include an ∼50% reduction in body weight and bone mass, and impaired longitudinal bone growth. Histological analysis showed reduced cortical and trabecular bone, suggesting cell-autonomous functions of FGF signaling during postnatal bone formation. Surprisingly, the double conditional knockout mice also showed growth plate defects and an arrest in chondrocyte proliferation. We provide genetic evidence of a non-cell-autonomous feedback pathway regulating Fgf9, Fgf18 and Pthlh expression, which led to increased expression and signaling of Fgfr3 in growth plate chondrocytes and suppression of chondrocyte proliferation. These observations show that FGF signaling in the osteoprogenitor lineage is obligately coupled to chondrocyte proliferation and the regulation of longitudinal bone growth. PMID:27052727

Moderate plasma activated media suppresses proliferation and migration of MDCK epithelial cells

NASA Astrophysics Data System (ADS)

Mohades, Soheila; Laroussi, Mounir; Maruthamuthu, Venkat

2017-05-01

Low-temperature plasma has been shown to have diverse biomedical uses, including its applications in cancer and wound healing. One recent approach in treating mammalian cells with plasma is through the use of plasma activated media (PAM), which is produced by exposing cell culture media to plasma. While the adverse effects of PAM treatment on cancerous epithelial cell lines have been recently studied, much less is known about the interaction of PAM with normal epithelial cells. In this paper, non-cancerous canine kidney MDCK (Madin-Darby Canine Kidney) epithelial cells were treated by PAM and time-lapse microscopy was used to directly monitor their proliferation and random migration upon treatment. While longer durations of PAM treatment led to cell death, we found that moderate levels of PAM treatment inhibited proliferation in these epithelial cells. We also found that PAM treatment reduced random cell migration within epithelial islands. Immunofluorescence staining showed that while there were no major changes in the actin/adhesion apparatus, there was a significant change in the nuclear localization of proliferation marker Ki-67, consistent with our time-lapse results.

The Practical Implementation of Non-Contacting Laser Strain Measurements Systems

NASA Technical Reports Server (NTRS)

Yunis, Isam; Quinn, roger D.; Kadambi, Jaikrishnan R.

2000-01-01

Measurement of stress and strain in rotating turbomachinery is critical to many industries. The search for a non-contacting, non-interfering, non-degrading measurement system is on going and extensive. While several methods seem promising in theory, implementation has proven troublesome. This work uncovers and quantifies these implementation issues in the context of a laser measurement system. Both a Laser Doppler Velocimeter system and a displacement laser system are utilized. It is found that the key issues are signal to noise ratio, rigid body compensation, measurement location, and conversion of intermittent measurements to a continuous signal. Accounting for these factors leads to successful measurements. These results should lead to better ideas and more practical solutions to the non-contacting, non-degrading, non-interfering strain measurement system problem.

Nuclear Symbiosis - A Means to Achieve Sustainable Nuclear Growth while Limiting the Spread of Sensititive Nuclear Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

David Shropshire

Global growth of nuclear energy in the 21st century is creating new challenges to limit the spread of nuclear technology without hindering adoption in countries now considering nuclear power. Independent nuclear states desire autonomy over energy choices and seek energy independence. However, this independence comes with high costs for development of new indigenous fuel cycle capabilities. Nuclear supplier states and expert groups have proposed fuel supply assurance mechanisms such as fuel take-back services, international enrichment services and fuel banks in exchange for recipient state concessions on the development of sensitive technologies. Nuclear states are slow to accept any concessions tomore » their rights under the Non-Proliferation Treaty. To date, decisions not to develop indigenous fuel cycle capabilities have been driven primarily by economics. However, additional incentives may be required to offset a nuclear state’s perceived loss of energy independence. This paper proposes alternative economic development incentives that could help countries decide to forgo development of sensitive nuclear technologies. The incentives are created through a nuclear-centered industrial complex with “symbiotic” links to indigenous economic opportunities. This paper also describes a practical tool called the “Nuclear Materials Exchange” for identifying these opportunities.« less

Wnt3a regulates proliferation and migration of HUVEC via canonical and non-canonical Wnt signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samarzija, Ivana; Sini, Patrizia; Schlange, Thomas

2009-08-28

Untangling the signaling pathways involved in endothelial cell biology is of central interest for the development of antiangiogenesis based therapies. Here we report that Wnt3a induces the proliferation and migration of HUVECs, but does not affect their survival. Wnt3a-induced proliferation was VEGFR signaling independent, but reduced upon CamKII inhibition. In a search for the downstream mediators of Wnt3a's effects on HUVEC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of {beta}-catenin. Moreover, under the same conditions we observed an upregulation in c-MYC, TIE-2 and GJA1 mRNA transcripts. Although treatment of HUVECs with Wnt5a induced DVL3more » phosphorylation, we did not observe any of the other effects seen upon Wnt3a stimulation. Taken together, our data indicate that Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration.« less

The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

PubMed Central

Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester

2016-01-01

Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells.

PubMed

Okusha, Yuka; Eguchi, Takanori; Sogawa, Chiharu; Okui, Tatsuo; Nakano, Keisuke; Okamoto, Kuniaki; Kozaki, Ken-Ichi

2018-05-15

Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. © 2018 Wiley Periodicals, Inc.

Immunohistochemical expression of protein 53, murine double minute 2, B-cell lymphoma 2, and proliferating cell nuclear antigen in odontogenic cysts and keratocystic odontogenic tumor.

PubMed

Galvão, Hebel Cavalcanti; Gordón-Núñez, Manuel Antonio; de Amorim, Rivadavio Fernandes Batista; Freitas, Roseana de Almeida; de Souza, Lelia Batista

2013-01-01

Even though odontogenic cysts share a similar histogenesis, they show different growth and differentiation profile due to differences in the proliferative cellular activity. We perform an immunohistochemical assessment of protein 53 (p53), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (bcl-2), and murine double minute 2 (MDM2) expression in odontogenic cysts and keratocystic odontogenic tumor analyzing their correlation with the biological behavior of these lesions. By the streptavidin-biotin-peroxidase method with antibodies against p53, PCNA, bcl-2, and MDM2 proteins, 11 radicular cysts, 11 dentigerous cysts, and 11 keratocystic odontogenic tumor were analyzed. The non-parametric Mann-Whitney U-test and Kruskall-Wallis test (P ≤ 0.05) were used to analyze the data. Immunopositivity for PCNA was observed in all cases appraised, predominantly in the suprabasal layer of keratocystic odontogenic tumor epithelial lining (SD ± 19.44), but no significant differences were found among the groups of lesions. Bcl-2 immunoexpression was observed especially in the basal layer of keratocystic odontogenic tumor. PCNA LI was significantly higher than bcl-2 LI in keratocystic odontogenic tumor. MDM2 and p53 immunoexpression were not detected in the lesions studied. Among the evaluated lesions, the keratocystic odontogenic tumor showed different immunoexpression of the proliferation and apoptosis markers. The results of this study suggest that the keratocystic odontogenic tumor presents distinct biological behavior of the odontogenic cysts, as for the processes of proliferation, apoptosis, and differentiation, reinforcing the information in favor of the neoplastic nature of this lesion.

Design and implementation of a simple nuclear power plant simulator

NASA Astrophysics Data System (ADS)

Miller, William H.

1983-02-01

A simple PWR nuclear power plant simulator has been designed and implemented on a minicomputer system. The system is intended for students use in understanding the power operation of a nuclear power plant. A PDP-11 minicomputer calculates reactor parameters in real time, uses a graphics terminal to display the results and a keyboard and joystick for control functions. Plant parameters calculated by the model include the core reactivity (based upon control rod positions, soluble boron concentration and reactivity feedback effects), the total core power, the axial core power distribution, the temperature and pressure in the primary and secondary coolant loops, etc.

Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells.

PubMed

Bullwinkel, Jörn; Baron-Lühr, Bettina; Lüdemann, Anja; Wohlenberg, Claudia; Gerdes, Johannes; Scholzen, Thomas

2006-03-01

The nuclear Ki-67 protein (pKi-67) has previously been shown to be exclusively expressed in proliferating cells. As a result, antibodies against this protein are widely used as prognostic tools in cancer diagnostics. Here we show, that despite the strong downregulation of pKi-67 expression in non-proliferating cells, the protein can nevertheless be detected at sites linked to ribosomal RNA (rRNA) synthesis. Although this finding does not argue against the use of pKi-67 as a proliferation marker, it has wide ranging implications for the elucidation of pKi-67 function. Employing the novel antibody TuBB-9, we could further demonstrate that also in proliferating cells, a fraction of pKi-67 is found at sites linked to the rRNA transcription machinery during interphase and mitosis. Moreover, chromatin immunoprecipitation (ChIP) assays provided evidence for a physical association of pKi-67 with chromatin of the promoter and transcribed region of the rRNA gene cluster. These data strongly suggest a role for pKi-67 in the early steps of rRNA synthesis. Copyright 2005 Wiley-Liss, Inc.

14 CFR § 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Implementation procedures by non-NASA... ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES (Eff. until 2-14-14) § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized...

The continuing risk of nuclear war.

PubMed

McCoy, Ronald

2007-01-01

Climate change and nuclear war are currently the most dangerous challenges to human civilisation and survival. The effects of climate change are now sufficient to persuade many governments to take effective measures to reduce greenhouse gas emissions. Today there are about 27,000 nuclear warheads, many at least ten times more powerful than the Hiroshima and Nagasaki bombs, and a meaningful medical response to a nuclear attack is impossible. Nevertheless, the threat of nuclear war does not raise public concern, and indeed the nuclear-weapon states are upgrading their capability. The only effective preventive measure is the abolition of nuclear weapons. Steps towards this include: a Fissile Material Cut-off Treaty, for the nuclear weapon states to observe their obligations under the Nuclear Non-Proliferation Treaty, and for the Comprehensive Test Ban Treaty to enter into force. The ultimate need is for a Nuclear Weapons Convention; International Physicians for the Prevention of Nuclear War have launched an International Campaign to Abolish Nuclear weapons (ICAN) to promote a NWC.

Advanced Quantification of Plutonium Ionization Potential to Support Nuclear Forensic Evaluations by Resonance Ionization Mass Spectrometry

DTIC Science & Technology

2015-06-01

Research Committee nm Nanometer Np Neptunium NPT Treaty of Non-proliferation of Nuclear Weapons ns Nanosecond ps Picosecond Pu Plutonium RIMS...discovery—credited also to Fritz Strassman— scientists realized these reactions also emitted secondary neutrons . These secondary neutrons could in...destructive capabilities of nuclear fission and atomic weapons . Figure 1. Uranium-235 Fission chain reaction, from [1

Non-Strategic Nuclear Targeting in a Non-Nuclear Army

DTIC Science & Technology

1994-06-03

their needs. After all, the nucler planners and target analysts at corps level must surely consider their preparedness an important issue. Also...controlled escalation (the nuclear signal) and its ability to apply nuclear power in a decisive manner. A hedge against the emergence of an overwhelming...manuals envision NSNF as powerful yet flexible alternatives to the more destabilizing strategic nuclear weapons. NSNF could be used as a show of

Long non-coding RNA AK093407 promotes proliferation and inhibits apoptosis of human osteosarcoma cells via STAT3 activation

PubMed Central

Wang, Yongkun; Liang, Tingting; Wang, Yao; Huang, Yan; Li, Ye

2017-01-01

Osteosarcoma is a malignant tumor of the skeletal system. Long non-coding RNAs (lncRNAs) have been shown to play significant role in osteosarcoma. The present study evaluated the effects and mechanism of lncRNA AK093407 in osteosarcoma. The study included human osteosarcoma cell line, U-2OS. Cell proliferation, viability, and apoptosis were measured using Ki-67 proliferation assay, MTT assay, and Annexin V/PI staining assay, respectively. Relative mRNA and protein expressions were measured using qRT-PCR and western blot, respectively. Interaction between AK093407 and STAT3 was identified using mass spectrometry and RNA pull-down assay. Results revealed that AK093407 was highly expressed in osteosarcoma cells and tissues. Then we demonstrated that overexpression of AK093407 promoted cell proliferation and viability and inhibited apoptosis, whereas suppression of AK093407 showed opposite effects. In addition, AK093407 regulated the expression of genes and proteins (Bcl-2, TGF-β, NF-κB, and PCNA) involved in the cell proliferation, viability, and apoptosis. Furthermore, we showed that AK093407 interacted with STAT3, and promoted its phosphorylation. Lastly, we showed that STAT3 activation was essential for the effects of AK093407 on cell proliferation and apoptosis as the overexpression of AK093407 in the presence of STAT3 inhibitor did not promote cell proliferation and inhibit cell apoptosis. AK093407 is highly expressed in osteosarcoma cells and tissues, and promotes cell proliferation and viability and inhibits apoptosis of osteosarcoma cell line U-2OS via STAT3 activation. PMID:28469961

Nuclear threat on the Korean peninsula: The present and the future. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S.

1994-04-01

Forty years after they were divided by the Cold War, South and North Korea are closer to reunification than ever before. However, North Korea's nuclear weapons program might cause South Koreans to be much less sure about reunification. Today the Cold War is over, but the Korean peninsula is still divided into two Koreas despite the new era of reconciliation. Since December 1991 when a non-aggression pact was signed barring nuclear weapons, North Korea has pursued its nuclear weapon development. In March 1993, North Korea declared its intention to withdraw from the Nuclear Non-Proliferation Treaty, and has been refusing amore » full inspection of its nuclear program. North Korea's nuclear issue is an international issue today. This paper discusses 'what threat we have today' and 'what should be done in the future.'.« less

Briefing Book. Volume 1: The Evolution of the Nuclear Non-Proliferation Regime (Fourth Edition).

DTIC Science & Technology

1998-01-01

usually termed) nuclear reactors. The first of these is that they contain a core or mass of fissile material (the fuel ) which may weigh tens of tons... HTGR is cooled with helium gas and moderated with graphite. Highly enriched uranium is used as fuel (93 per cent U-235), though this may be mixed with...to convert U-238 in a blanket around the core into Pu-239 at a rate faster than its own consumption of fissile material. They thus produce more fuel

Implementation guideline for non-freeway centerline rumble strips.

DOT National Transportation Integrated Search

2015-03-01

This document presents a guideline for the : implementation of non-freeway centerline rumble : strips on high speed rural highways. It includes : recommended practices, according to MDOT : standards, and describes effective strategies and : technique...

Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis.

PubMed

Chen, Pengguo; Li, Jie; Huo, Yan; Lu, Jin; Wan, Lili; Li, Bin; Gan, Run; Guo, Cheng

2015-01-01

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis, which is a pathological process characterized by extracellular matrix accumulation. NR4A2 is a nuclear receptor belonging to the NR4A subfamily and vital in regulating cell growth, metabolism, inflammation and other biological functions. However, its role in HSCs is unclear. We analyzed NR4A2 expression in fibrotic liver and stimulated HSCs compared with control group and studied the influence on cell proliferation, cell cycle, cell apoptosis and MAPK pathway after NR4A2 knockdown. NR4A2 expression was examined by real-time polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence analyses. NR4A2 expression was significantly lower in fibrotic liver tissues and PDGF BB or TGF-β stimulated HSCs compared with control group. After NR4A2 knockdown α-smooth muscle actin and Col1 expression increased. In addition, NR4A2 silencing led to the promotion of cell proliferation, increase of cell percentage in S phase and reduced phosphorylation of ERK1/2, P38 and JNK in HSCs. These results indicate that NR4A2 can inhibit HSC proliferation through MAPK pathway and decrease extracellular matrix in liver fibrogenesis. NR4A2 may be a promising therapeutic target for liver fibrosis.

Tritium as an indicator of venues for nuclear tests.

PubMed

Lyakhova, O N; Lukashenko, S N; Mulgin, S I; Zhdanov, S V

2013-10-01

Currently, due to the Treaty on the Non-proliferation of Nuclear Weapons there is a highly topical issue of an accurate verification of nuclear explosion venues. This paper proposes to consider new method for verification by using tritium as an indicator. Detailed studies of the tritium content in the air were carried in the locations of underground nuclear tests - "Balapan" and "Degelen" testing sites located in Semipalatinsk Test Site. The paper presents data on the levels and distribution of tritium in the air where tunnels and boreholes are located - explosion epicentres, wellheads and tunnel portals, as well as in estuarine areas of the venues for the underground nuclear explosions (UNE). Copyright © 2013 Elsevier Ltd. All rights reserved.

Leo Szilard Lectureship Award Talk: Controlling and eliminating nuclear-weapon materials

NASA Astrophysics Data System (ADS)

von Hippel, Frank

2010-02-01

Fissile material -- in practice plutonium and highly enriched uranium (HEU) -- is the essential ingredient in nuclear weapons. Controlling and eliminating fissile material and the means of its production is therefore the common denominator for nuclear disarmament, nuclear non-proliferation and the prevention of nuclear terrorism. From a fundamentalist anti-nuclear-weapon perspective, the less fissile material there is and the fewer locations where it can be found, the safer a world we will have. A comprehensive fissile-material policy therefore would have the following elements: *Consolidation of all nuclear-weapon-usable materials at a minimum number of high-security sites; *A verified ban on the production of HEU and plutonium for weapons; *Minimization of non-weapon uses of HEU and plutonium; and *Elimination of all excess stocks of plutonium and HEU. There is activity on all these fronts but it is not comprehensive and not all aspects are being pursued vigorously or competently. It is therefore worthwhile to review the situation. )

Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage.

PubMed

Waraky, Ahmed; Lin, Yingbo; Warsito, Dudi; Haglund, Felix; Aleem, Eiman; Larsson, Olle

2017-11-03

We have previously shown that the insulin-like growth factor 1 receptor (IGF-1R) translocates to the cell nucleus, where it binds to enhancer-like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF-1R (nIGF-1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer-binding factor 1 (Lef1), histone H3, and Brahma-related gene-1 proteins. In this study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF-1R-binding partner. PCNA is a pivotal component of the replication fork machinery and a main regulator of the DNA damage tolerance (DDT) pathway. We found that IGF-1R interacts with and phosphorylates PCNA in human embryonic stem cells and other cell lines. In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination. Co-immunoprecipitation experiments suggested that these ubiquitination events may be mediated by DDT-dependent E2/E3 ligases ( e.g. RAD18 and SHPRH/HLTF). Absence of IGF-1R or mutation of Tyr-60, Tyr-133, or Tyr-250 in PCNA abrogated its ubiquitination. Unlike in cells expressing IGF-1R, externally induced DNA damage in IGF-1R-negative cells caused G 1 cell cycle arrest and S phase fork stalling. Taken together, our results suggest a role of IGF-1R in DDT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Applications of nuclear physics

NASA Astrophysics Data System (ADS)

Hayes, A. C.

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

DOE PAGES

Hayes-Sterbenz, Anna Catherine

2017-01-10

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Applications of nuclear physics.

PubMed

Hayes, A C

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayes-Sterbenz, Anna Catherine

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Old foes, new understandings: nuclear entry of small non-enveloped DNA viruses.

PubMed

Fay, Nikta; Panté, Nelly

2015-06-01

The nuclear import of viral genomes is an important step of the infectious cycle for viruses that replicate in the nucleus of their host cells. Although most viruses use the cellular nuclear import machinery or some components of this machinery, others have developed sophisticated ways to reach the nucleus. Some of these have been known for some time; however, recent studies have changed our understanding of how some non-enveloped DNA viruses access the nucleus. For example, parvoviruses enter the nucleus through small disruptions of the nuclear membranes and nuclear lamina, and adenovirus tugs at the nuclear pore complex, using kinesin-1, to disassemble their capsids and deliver viral proteins and genomes into the nucleus. Here we review recent findings of the nuclear import strategies of three small non-enveloped DNA viruses, including adenovirus, parvovirus, and the polyomavirus simian virus 40. Copyright © 2015 Elsevier B.V. All rights reserved.

The new politics of missile proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karp, A.

1996-10-01

The author addresses the most consequential proliferation battle of the 1990s which occurred in Washington over the interpretation of the long-term threat to the United States from ballistic missiles. In the early 1970s, the stabilization of the US-Soviet strategic relationship led to new disputes over the other side`s future intentions, seen most graphically in Western debates over the implications of the Soviet SS-18 and SS-20 missile programs. Today, in much the same way, proliferation politics has matured to the point that surprises are few and the most challenging problem is anticipating the more distant future. Washington`s ballistic missile proliferation battlemore » was sparked by National Intelligence Estimate (NIE) 95-19, entitled {open_quotes}Emerging Threats to North America During the Next 15 Years,{close_quotes} released by the National Intelligence Council in November 1995. This document updated the evidence of regional missile programs reviewed in a similar report issued in 1993, and recapitulated the previous finding that {open_quotes}No country, other than the major declared nuclear powers, will develop or otherwise acquire a ballistic missile in the next 15 years that could threatened the contiguous 48 states or Canada.{close_quotes} The new report confirmed what several other studies of missile proliferation had already established: that besides the five nuclear-weapon states (the United States, Russia, China, France and Britain), only India, Israel and Japan are in a position to develop an ICBM during the foreseeable future, and while all have relevant capabilities, none are undertaking the steps necessary to develop an actual ICBM.« less

Non-Thermal Atmospheric Pressure Plasma Efficiently Promotes the Proliferation of Adipose Tissue-Derived Stem Cells by Activating NO-Response Pathways

PubMed Central

Park, Jeongyeon; Lee, Hyunyoung; Lee, Hae June; Kim, Gyoo Cheon; Kim, Do Young; Han, Sungbum; Song, Kiwon

2016-01-01

Non-thermal atmospheric pressure plasma (NTAPP) is defined as a partially ionized gas with electrically charged particles at atmospheric pressure. Our study showed that exposure to NTAPP generated in a helium-based dielectric barrier discharge (DBD) device increased the proliferation of adipose tissue-derived stem cells (ASCs) by 1.57-fold on an average, compared with untreated cells at 72 h after initial NTAPP exposure. NTAPP-exposed ASCs maintained their stemness, capability to differentiate into adipocytes but did not show cellular senescence. Therefore, we suggested that NTAPP can be used to increase the proliferation of ASCs without affecting their stem cell properties. When ASCs were exposed to NTAPP in the presence of a nitric oxide (NO) scavenger, the proliferation-enhancing effect of NTAPP was not obvious. Meanwhile, the proliferation of NTAPP-exposed ASCs was not much changed in the presence of scavengers for reactive oxygen species (ROS). Also, Akt, ERK1/2, and NF-κB were activated in ASCs after NTAPP exposure. These results demonstrated that NO rather than ROS is responsible for the enhanced proliferation of ASCs following NTAPP exposure. Taken together, this study suggests that NTAPP would be an efficient tool for use in the medical application of ASCs both in vitro and in vivo. PMID:27991548

Strengthening the nuclear nonproliferation regime : focus on the civilian nuclear fuel cycle.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saltiel, David H.; Pregenzer, Arian Leigh

2005-04-01

Leaders around the world and across the ideological spectrum agree that the global nonproliferation regime is facing a serious test. The emergence of sophisticated terrorist networks, black markets in nuclear technology, and technological leaps associated with globalization have conspired to threaten one of the most successful examples of international cooperation in history. The rampant proliferation of nuclear weapons that was predicted at the start of the nuclear age has been largely held in check and the use of those weapons avoided. Nonetheless, with the thirty-fifth anniversary of the Treaty on the Nonproliferation of Nuclear Weapons (NPT), the threat of nuclearmore » proliferation seems more serious than ever. Although experts readily concede that there exist many pathways to proliferation, the threat posed by the misuse of the civilian nuclear fuel cycle has received considerable recent attention. While the connection between nuclear energy and nonproliferation has been a topic of discussion since the dawn of the nuclear age, world events have brought the issue to the forefront once again. United States President George W. Bush and International Atomic Energy Agency (IAEA) Director General Mohammad ElBaradei are among those who have highlighted proliferation risks associated with civilian nuclear power programs and called for revitalizing the nuclear nonproliferation regime to address new threats. From the possibility of diversion or theft of nuclear material or technology, to the use of national civilian programs as a cover for weapons programs - what some have called latent proliferation - the fuel cycle appears to many to represent a glaring proliferation vulnerability. Just as recognition of these risks is not new, neither is recognition of the many positive benefits of nuclear energy. In fact, a renewed interest in exploiting these benefits has increased the urgency of addressing the risks. Global energy demand is expected to at least double by the

Schools and Non-Nuclear Families: Recasting Relationships.

ERIC Educational Resources Information Center

Shea, Catherine A.

The soundness of the home-school relationship depends on mutual trust and understanding. This relationship is now at risk because schools have not adjusted to single-parent and step-families. Concern about the home-school relationship has increased over the last decade. However, accompanying the recent rise in non-nuclear families is a gap in…

Social Data Analysis by Non-Linear Imbedding

DTIC Science & Technology

2013-09-20

Fig. 1 shows this dimenion-reduced galaxy. This example is chosen to illustrate how our “ history independent” techniques can infer major historical...DISTRIBUTION A: Distribution approved for public release. 1989 1990 1991 Middle East 2 7 6 Weapon Nonproliferation 2 6 5 Anti- Apartheid & Human Rights...the Non-Proliferation of Nuclear Weapons) #3570 (Status of the International Convention on the Suppression and Punishment of the crime of Apartheid

A proliferation of nuclear waste for the Southeast.

PubMed

Alvarez, Robert; Smith, Stephen

2007-12-01

The U.S. Department of Energy's (DOE) Global Nuclear Energy Partnership (GNEP) is being promoted as a program to bring about the expansion of worldwide nuclear energy. Here in the U.S. much of this proposed nuclear power expansion is slated to happen in the Southeast, including here in South Carolina. Under the GNEP plan, the United States and its nuclear partners would sell nuclear power plants to developing nations that agree not to pursue technologies that would aid nuclear weapons production, notably reprocessing and uranium enrichment. As part of the deal, the United States would take highly radioactive spent ("used") fuel rods to a reprocessing center in this country. Upon analysis of the proposal, it is clear that DOE lacks a credible plan for the safe management and disposal of radioactive wastes stemming from the GNEP program and that the high costs and possible public health and environmental impacts from the program pose significant risks, especially to this region. Given past failures to address waste problems before they were created, DOE's rush to invest major public funds for deployment of reprocessing should be suspended.

Non-nuclear methods for HMA density measurements : final report, June 2008.

DOT National Transportation Integrated Search

2008-05-01

Non-nuclear methods for the measurement of hot-mix asphalt (HMA) density offer the ability to take numerous density readings in a very short period of time, without the need for intensive licensing, training, and maintenance efforts common to nuclear...

High Fidelity Thermal Simulators for Non-Nuclear Testing: Analysis and Initial Results

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Dickens, Ricky; Dixon, David

2007-01-01

Non-nuclear testing can be a valuable tool in the development of a space nuclear power system, providing system characterization data and allowing one to work through various fabrication, assembly and integration issues without the cost and time associated with a full ground nuclear test. In a non-nuclear test bed, electric heaters are used to simulate the heat from nuclear fuel. Testing with non-optimized heater elements allows one to assess thermal, heat transfer, and stress related attributes of a given system, but fails to demonstrate the dynamic response that would be present in an integrated, fueled reactor system. High fidelity thermal simulators that match both the static and the dynamic fuel pin performance that would be observed in an operating, fueled nuclear reactor can vastly increase the value of non-nuclear test results. With optimized simulators, the integration of thermal hydraulic hardware tests with simulated neutronie response provides a bridge between electrically heated testing and fueled nuclear testing, providing a better assessment of system integration issues, characterization of integrated system response times and response characteristics, and assessment of potential design improvements' at a relatively small fiscal investment. Initial conceptual thermal simulator designs are determined by simple one-dimensional analysis at a single axial location and at steady state conditions; feasible concepts are then input into a detailed three-dimensional model for comparison to expected fuel pin performance. Static and dynamic fuel pin performance for a proposed reactor design is determined using SINDA/FLUINT thermal analysis software, and comparison is made between the expected nuclear performance and the performance of conceptual thermal simulator designs. Through a series of iterative analyses, a conceptual high fidelity design can developed. Test results presented in this paper correspond to a "first cut" simulator design for a potential

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

PubMed

Kim, Dong-Kyu; Jin, Hong Ryul; Eun, Kyoung Mi; Mutusamy, Somasundran; Cho, Seong H; Oh, Sohee; Kim, Dae Woo

2015-01-01

Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear. A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed. We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the

Analysis of space reactor system components: Investigation through simulation and non-nuclear testing

NASA Astrophysics Data System (ADS)

Bragg-Sitton, Shannon M.

The use of fission energy in space power and propulsion systems offers considerable advantages over chemical propulsion. Fission provides over six orders of magnitude higher energy density, which translates to higher vehicle specific impulse and lower specific mass. These characteristics enable ambitious space exploration missions. The natural space radiation environment provides an external source of protons and high energy, high Z particles that can result in the production of secondary neutrons through interactions in reactor structures. Applying the approximate proton source in geosynchronous orbit during a solar particle event, investigation using MCNPX 2.5.b for proton transport through the SAFE-400 heat pipe cooled reactor indicates an incoming secondary neutron current of (1.16 +/- 0.03) x 107 n/s at the core-reflector interface. This neutron current may affect reactor operation during low power maneuvers (e.g., start-up) and may provide a sufficient reactor start-up source. It is important that a reactor control system be designed to automatically adjust to changes in reactor power levels, maintaining nominal operation without user intervention. A robust, autonomous control system is developed and analyzed for application during reactor start-up, accounting for fluctuations in the radiation environment that result from changes in vehicle location or to temporal variations in the radiation field. Development of a nuclear reactor for space applications requires a significant amount of testing prior to deployment of a flight unit. High confidence in fission system performance can be obtained through relatively inexpensive non-nuclear tests performed in relevant environments, with the heat from nuclear fission simulated using electric resistance heaters. A series of non-nuclear experiments was performed to characterize various aspects of reactor operation. This work includes measurement of reactor core deformation due to material thermal expansion and

Proliferative activity of denture-induced fibrous inflammatory hyperplasia analyzed by proliferating cell nuclear antigen labeling index.

PubMed

Coelho, C M; Zucoloto, S

1999-01-01

Denture-induced fibrous inflammatory hyperplasia (FIH) occurs around the borders of an ill-fitting denture. There has been no report in the literature concerning epithelial proliferative activity in FIH. The purpose of this study was to observe the labeling of proliferating cell nuclear antigen (PCNA) and evaluate its clinicopathologic results. The labeling index (LI) was assessed by using the PCNA, a nuclear protein synthesized mainly in the G1-S stages of the cell cycle that could be detected immunohistochemically by the monoclonal antibody PC10. The PCNA LI was assessed in FIH specimens, in clinically normal specimens 1 cm from the FIH margin (adjacent group), and in clinically normal specimens located at least 2 cm from the adjacent group; the last were considered the control group. The mean PCNA LI values in the basal, parabasal, and overall epithelial layers were similar in FIH and in the adjacent group and were significantly higher than in the control group. These data support the importance of the surgical treatment of FIH with wide excision (about 1 cm) since the clinically normal tissue around the lesion could be histologically altered.

National Center for Nuclear Security - NCNS

ScienceCinema

None

2018-01-16

As the United States embarks on a new era of nuclear arms control, the tools for treaty verification must be accurate and reliable, and must work at stand-off distances. The National Center for Nuclear Security, or NCNS, at the Nevada National Security Site, is poised to become the proving ground for these technologies. The center is a unique test bed for non-proliferation and arms control treaty verification technologies. The NNSS is an ideal location for these kinds of activities because of its multiple environments; its cadre of experienced nuclear personnel, and the artifacts of atmospheric and underground nuclear weapons explosions. The NCNS will provide future treaty negotiators with solid data on verification and inspection regimes and a realistic environment in which future treaty verification specialists can be trained. Work on warhead monitoring at the NCNS will also support future arms reduction treaties.

Nuclear Proliferation in the Middle East: In Pursuit of a Regional Logic

DTIC Science & Technology

the Cold War allowed the sole superpower, the United States, to better manage proliferation issues and strengthen existing or create new multilateral...mechanisms to control these threats. In the recent, less structured multipolar environment, great powers came together to manage proliferation with their efforts bolstered by the nonproliferation regime.

Neutronics calculations on the impact of burnable poisons to safety and non-proliferation aspects of inert matrix fuel

NASA Astrophysics Data System (ADS)

Pistner, C.; Liebert, W.; Fujara, F.

2006-06-01

Inert matrix fuels (IMF) with plutonium may play a significant role to dispose of stockpiles of separated plutonium from military or civilian origin. For reasons of reactivity control of such fuels, burnable poisons (BP) will have to be used. The impact of different possible BP candidates (B, Eu, Er and Gd) on the achievable burnup as well as on safety and non-proliferation aspects of IMF are analyzed. To this end, cell burnup calculations have been performed and burnup dependent reactivity coefficients (boron worth, fuel temperature and moderator void coefficient) were calculated. All BP candidates were analyzed for one initial BP concentration and a range of different initial plutonium-concentrations (0.4-1.0 g cm-3) for reactor-grade plutonium isotopic composition as well as for weapon-grade plutonium. For the two most promising BP candidates (Er and Gd), a range of different BP concentrations was investigated to study the impact of BP concentration on fuel burnup. A set of reference fuels was identified to compare the performance of uranium-fuels, MOX and IMF with respect to (1) the fraction of initial plutonium being burned, (2) the remaining absolute plutonium concentration in the spent fuel and (3) the shift in the isotopic composition of the remaining plutonium leading to differences in the heat and neutron rate produced. In the case of IMF, the remaining Pu in spent fuel is unattractive for a would be proliferator. This underlines the attractiveness of an IMF approach for disposal of Pu from a non-proliferation perspective.

Implementing an Information Security Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glantz, Clifford S.; Lenaeus, Joseph D.; Landine, Guy P.

The threats to information security have dramatically increased with the proliferation of information systems and the internet. Chemical, biological, radiological, nuclear, and explosives (CBRNe) facilities need to address these threats in order to protect themselves from the loss of intellectual property, theft of valuable or hazardous materials, and sabotage. Project 19 of the European Union CBRN Risk Mitigation Centres of Excellence Initiative is designed to help CBRN security managers, information technology/cybersecurity managers, and other decision-makers deal with these threats through the application of cost-effective information security programs. Project 19 has developed three guidance documents that are publically available to covermore » information security best practices, planning for an information security management system, and implementing security controls for information security.« less

Strengthening Biosecurity in Iraq: Development of a National Biorisk Management System

PubMed Central

Al Jewari, Mahdi F. H.; Koblentz, Gregory D.

2016-01-01

Since 2004, the Republic of Iraq has undertaken a concerted effort to comply with all of its international obligations to prevent the proliferation and the use of chemical, biological, radiological, and nuclear (CBRN) weapons. A centerpiece of this effort is Iraq’s development of a National Biorisk Management System. The Iraqi National Monitoring Authority (INMA), which is responsible for CBRN security and non-proliferation in Iraq, has played a key role in establishing this system. This article provides an overview of Iraq’s international non-proliferation commitments, describes the legal and organizational steps it has taken to implement these commitments, and examines current initiatives to strengthen Iraq’s biosecurity. PMID:26952002

Realistic Development and Testing of Fission System at a Non-Nuclear Testing Facility

NASA Technical Reports Server (NTRS)

Godfroy, Tom; VanDyke, Melissa; Dickens, Ricky; Pedersen, Kevin; Lenard, Roger; Houts, Mike

2000-01-01

The use of resistance heaters to simulate heat from fission allows extensive development of fission systems to be performed in non-nuclear test facilities, saving time and money. Resistance heated tests on a module has been performed at the Marshall Space Flight Center in the Propellant Energy Source Testbed (PEST). This paper discusses the experimental facilities and equipment used for performing resistance heated tests. Recommendations are made for improving non-nuclear test facilities and equipment for simulated testing of nuclear systems.

Realistic development and testing of fission systems at a non-nuclear testing facility

NASA Astrophysics Data System (ADS)

Godfroy, Tom; van Dyke, Melissa; Dickens, Ricky; Pedersen, Kevin; Lenard, Roger; Houts, Mike

2000-01-01

The use of resistance heaters to simulate heat from fission allows extensive development of fission systems to be performed in non-nuclear test facilities, saving time and money. Resistance heated tests on a module has been performed at the Marshall Space Flight Center in the Propellant Energy Source Testbed (PEST). This paper discusses the experimental facilities and equipment used for performing resistance heated tests. Recommendations are made for improving non-nuclear test facilities and equipment for simulated testing of nuclear systems. .

Targeting of Several Glycolytic Enzymes Using RNA Interference Reveals Aldolase Affects Cancer Cell Proliferation through a Non-glycolytic Mechanism

PubMed Central

Lew, Carolyn Ritterson; Tolan, Dean R.

2012-01-01

In cancer, glucose uptake and glycolysis are increased regardless of the oxygen concentration in the cell, a phenomenon known as the Warburg effect. Several (but not all) glycolytic enzymes have been investigated as potential therapeutic targets for cancer treatment using RNAi. Here, four previously untargeted glycolytic enzymes, aldolase A, glyceraldehyde 3-phosphate dehydrogenase, triose phosphate isomerase, and enolase 1, are targeted using RNAi in Ras-transformed NIH-3T3 cells. Of these enzymes, knockdown of aldolase causes the greatest effect, inhibiting cell proliferation by 90%. This defect is rescued by expression of exogenous aldolase. However, aldolase knockdown does not affect glycolytic flux or intracellular ATP concentration, indicating a non-metabolic cause for the cell proliferation defect. Furthermore, this defect could be rescued with an enzymatically dead aldolase variant that retains the known F-actin binding ability of aldolase. One possible model for how aldolase knockdown may inhibit transformed cell proliferation is through its disruption of actin-cytoskeleton dynamics in cell division. Consistent with this hypothesis, aldolase knockdown cells show increased multinucleation. These results are compared with other studies targeting glycolytic enzymes with RNAi in the context of cancer cell proliferation and suggest that aldolase may be a useful target in the treatment of cancer. PMID:23093405

Effects of Non-Collagenous Proteins, TGF-β1, and PDGF-BB on Viability and Proliferation of Dental Pulp Stem Cells

PubMed Central

Tabatabaei, Fahimeh Sadat

2016-01-01

ABSTRACT Objectives The dentin matrix servers as a reservoir of growth factors, sequestered during dentinogenesis. The aim of this study was to assess the viability and proliferation of dental pulp stem cells in the presence of dentin matrix-derived non-collagenous proteins and two growth factors; platelet-derived growth factor BB and transforming growth factor beta 1. Material and Methods The dental pulp cells were isolated and cultured. The dentin proteins were extracted and purified. The MTT assay was performed for assessment of cell viability and proliferation in the presence of different concentrations of dentin proteins and growth factors during 24 - 72 h post-treatment. Results The cells treated with 250 ng/mL dentin proteins had the best viability and proliferation ability in comparison with other concentrations (P < 0.05). The MTT assay demonstrated that cells cultured with 5 ng/mL platelet-derived growth factor BB had the highest viability at each time point as compared to other groups (P < 0.05). However, in presence of platelet-derived growth factor BB alone and in combination with transforming growth factor beta 1 and dentin proteins (10 ng/mL), significant higher viability was seen at all time points (P < 0.05). The least viability and proliferation at each growth factor concentration was seen in cells treated with combination of transforming growth factor beta 1 and dentin proteins at 72 h (P < 0.05). Conclusions The results indicated that the triple combination of growth factors and matrix-derived non-collagenous proteins (especially at 10 ng/mL concentration) has mitogenic effect on dental pulp stem cells. PMID:27099698

GM-CSF produced by non-hematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa1,2

PubMed Central

Egea, Laia; McAllister, Christopher S.; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.

2012-01-01

GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, and dendritic cell (DC) differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn’s disease in humans and colitis in murine models has been considered mainly to reflect its activity on myeloid cells. We used GM-CSF deficient (GM-CSF−/−) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS) at doses that resulted in little epithelial damage and mucosal ulceration in wild type (WT) mice resulted in marked colon ulceration and delayed ulcer healing in GM-CSF−/− mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF−/− mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF−/− mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Non-hematopoietic cells and not myeloid cells produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury as revealed by bone marrow chimera and DC depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell produced GM-CSF has a novel non-redundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium. PMID:23325885

Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

PubMed

Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

2017-03-02

The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance.

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2012-06-26

145 Abdul Mannan, “Preventing Nuclear Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or a Commercial ...Pakistan’s Civil Nuclear Program.” Some analysts argue that spent nuclear fuel is more vulnerable when being transported . 146 Martellini, 2008. 147...produced fissile material for its nuclear weapons using gas-centrifuge-based uranium enrichment technology, which it mastered by the mid-1980s

Going nuclear: The spread of nuclear weapons 1986-1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spector, L.S.

1987-01-01

In the third annual report of the Carnegie Endowment for International Peace on the spread of nuclear weapons, Spector provides a critical survey of the status of nuclear proliferation throughout the world and examines the nuclear potential of nations in the Middle East, Asia, Africa, and Latin America. Drawing on both historical documents and up-to-date reports, the author addresses such specific topics as Israel's nuclear arsenal, nuclear terrorism and its global security implications, arms control and nuclear safeguards, international treaties, weapons buildup, and political radicalism and unrest in nuclear-threshold nations.

Enhancing BWR proliferation resistance fuel with minor actinides

NASA Astrophysics Data System (ADS)

Chang, Gray S.

2009-03-01

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

Cell cycles and proliferation patterns in Haematococcus pluvialis

NASA Astrophysics Data System (ADS)

Zhang, Chunhui; Liu, Jianguo; Zhang, Litao

2017-09-01

Most studies on Haematococcus pluvialis have been focused on cell growth and astaxanthin accumulation; far less attention has been paid to cell cycles and proliferation patterns. The purpose of this study was to clarify cell cycles and proliferation patterns in H. pluvialis microscopically using a camera and video recorder system. The complicated life history of H. pluvialis can be divided into two stages: the motile stage and the non-motile stage. All the cells can be classified into forms as follows: motile cell, nonmotile cell, zoospore and aplanospore. The main cell proliferation, both in the motile phase and non-motile phase in H. pluvialis, is by asexual reproduction. Under normal growth conditions, a motile cell usually produces two, sometimes four, and exceptionally eight zoospores. Under unfavorable conditions, the motile cell loses its flagella and transforms into a non-motile cell, and the non-motile cell usually produces 2, 4 or 8 aplanospores, and occasionally 20-32 aplanospores, which further develop into non-motile cells. Under suitable conditions, the non-motile cell is also able to release zoospores. The larger non-motile cells produce more than 16 zoospores, and the smaller ones produce 4 or 8 zoospores. Vegetative reproduction is by direct cell division in the motile phase and by occasional cell budding in the non-motile phase. There is, as yet, no convincing direct evidence for sexual reproduction.

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2009-12-09

Nuclear Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008...gave additional urgency to the program. Pakistan produced fissile material for its nuclear weapons using gas-centrifuge-based uranium enrichment...technology, which it mastered by the mid-1980s. Highly-enriched uranium (HEU) is one of two types of fissile material used in nuclear weapons; the other

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2009-10-15

and technical measures to prevent unauthorized or accidental use of nuclear weapons, as well as contribute to physical security of storage ...Talks On Nuclear Security,” The Boston Globe, May 5, 2009. 79 Abdul Mannan, “Preventing Nuclear Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or...a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008; Martellini, 2008. 80 Martellini, 2008. 81 For more information

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2012-05-10

2009. 143 Abdul Mannan, “Preventing Nuclear Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or a Commercial Irradiation Source in Transport ,” in...Program.” Some analysts argue that spent nuclear fuel is more vulnerable when being transported . 144 Martellini, 2008. Pakistan’s Nuclear Weapons...urgency to the program. Pakistan produced fissile material for its nuclear weapons using gas-centrifuge-based uranium enrichment technology, which it

Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation

PubMed Central

Lunt, Sophia Y.; Muralidhar, Vinayak; Hosios, Aaron M.; Israelsen, William J.; Gui, Dan Y.; Newhouse, Lauren; Ogrodzinski, Martin; Hecht, Vivian; Xu, Kali; Acevedo, Paula N. Marín; Hollern, Daniel P.; Bellinger, Gary; Dayton, Talya L.; Christen, Stefan; Elia, Ilaria; Dinh, Anh T.; Stephanopoulos, Gregory; Manalis, Scott R.; Yaffe, Michael B.; Andrechek, Eran R.; Fendt, Sarah-Maria; Heiden, Matthew G. Vander

2014-01-01

SUMMARY Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2-deletion affects proliferation and metabolism in non-transformed, non-immortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis. PMID:25482511

Evidence for a role of Collapsin response mediator protein-2 in signaling pathways that regulate the proliferation of non-neuronal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tahimic, Candice Ginn T.; Tomimatsu, Nozomi; Nishigaki, Ryuichi

Collapsin response mediator protein-2 or Crmp-2 plays a critical role in the establishment of neuronal polarity. In this study, we present evidence that apart from its functions in neurodevelopment, Crmp-2 is also involved in pathways that regulate the proliferation of non-neuronal cells through its phosphorylation by regulatory proteins. We show that Crmp-2 undergoes dynamic phosphorylation changes in response to contact inhibition-induced quiescence and that hyperphosphorylation of Crmp-2 occurs in a tumor. We further suggest that de-regulation of Crmp-2 phosphorylation levels at certain amino acid residues may lead to aberrant cell proliferation and consequently, tumorigenesis.

Inhibition of Smooth Muscle Proliferation by Urea-Based Alkanoic Acids via Peroxisome Proliferator-Activated Receptor α–Dependent Repression of Cyclin D1

PubMed Central

Ng, Valerie Y.; Morisseau, Christophe; Falck, John R.; Hammock, Bruce D.; Kroetz, Deanna L.

2007-01-01

Objective Proliferation of smooth muscle cells is implicated in cardiovascular complications. Previously, a urea-based soluble epoxide hydrolase inhibitor was shown to attenuate smooth muscle cell proliferation. We examined the possibility that urea-based alkanoic acids activate the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and the role of PPARα in smooth muscle cell proliferation. Methods and Results Alkanoic acids transactivated PPARα, induced binding of PPARα to its response element, and significantly induced the expression of PPARα-responsive genes, showing their function as PPARα agonists. Furthermore, the alkanoic acids attenuated platelet-derived growth factor–induced smooth muscle cell proliferation via repression of cyclin D1 expression. Using small interfering RNA to decrease endogenous PPARα expression, it was determined that PPARα was partially involved in the cyclin D1 repression. The antiproliferative effects of alkanoic acids may also be attributed to their inhibitory effects on soluble epoxide hydrolase, because epoxyeicosatrienoic acids alone inhibited smooth muscle cell proliferation. Conclusions These results show that attenuation of smooth muscle cell proliferation by urea-based alkanoic acids is mediated, in part, by the activation of PPARα. These acids may be useful for designing therapeutics to treat diseases characterized by excessive smooth muscle cell proliferation. PMID:16917105

A Strategy for Nuclear Energy Research and Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ralph G. Bennett

2008-12-01

The United States is facing unprecedented challenges in climate change and energy security. President-elect Obama has called for a reduction of CO2 emissions to 1990 levels by 2020, with a further 80% reduction by 2050. Meeting these aggressive goals while gradually increasing the overall energy supply requires that all non-emitting technologies must be advanced. The development and deployment of nuclear energy can, in fact, help the United States meet several key challenges: 1) Increase the electricity generated by non-emitting sources to mitigate climate change, 2) Foster the safe and proliferation-resistant use of nuclear energy throughout the world, 3) Reduce themore » transportation sector’s dependence on imported fossil fuels, and 4) Reduce the demand on natural gas for process heat and hydrogen production. However, because of the scale, cost, and time horizons involved, increasing nuclear energy’s share will require a coordinated research effort—combining the efforts of industry and government, supported by innovation from the research community. This report outlines the significant nuclear energy research and development (R&D) necessary to create options that will allow government and industrial decision-makers to set policies and create nuclear energy initiatives that are decisive and sustainable. The nuclear energy R&D strategy described in this report adopts the following vision: Safe and economical nuclear energy in the United States will expand to address future electric and non-electric needs, significantly reduce greenhouse gas emissions and provide energy diversity, while providing leadership for safe, secure and responsible expansion of nuclear energy internationally.« less

Implementation of Quantum Private Queries Using Nuclear Magnetic Resonance

NASA Astrophysics Data System (ADS)

Wang, Chuan; Hao, Liang; Zhao, Lian-Jie

2011-08-01

We present a modified protocol for the realization of a quantum private query process on a classical database. Using one-qubit query and CNOT operation, the query process can be realized in a two-mode database. In the query process, the data privacy is preserved as the sender would not reveal any information about the database besides her query information, and the database provider cannot retain any information about the query. We implement the quantum private query protocol in a nuclear magnetic resonance system. The density matrix of the memory registers are constructed.

Toward a nuclear-weapon-free world: a Chinese perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, D.

In the present article, the author addresses China's policy on proliferation and nuclear testing. China, after observing an unannounced moratorium for more than a year, conducted a test last October, and maintains that it cannot exclude the need to carry out a few more tests for a certain period of time for national defense. The author discusses reasons for future tests. He suggests that a major factor in the testing may be to improve the safety and reliability of the present Chinese arsenal. He believes that whether or not China continues to test nuclear weapons will depend upon the balancemore » of different national interests as perceived by the Chinese government. Following the underground test in Xinjiang province last October, the Chinese government issued a letter to U.N. Secretary-General Boutros Boutros-Ghali saying that it was entirely for the purpose of self-defense that China developed and possessed a small number of nuclear weapons, and that it had always exercised utmost restraint on nuclear testing. The letter also states that [open quotes]after a comprehensive test ban treaty is concluded and comes into effect, China will abide by it and carry out no more nuclear tests.[close quotes] The author concludes that an international treaty banning nuclear weapons tests is important, but a no-first-use agreement would be just as useful. He discusses options for effecting a world-wide non-proliferation policy.« less

Nuclear regulatory legislation: 102d Congress. Volume 1, No. 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-10-01

This document is a compilation of nuclear regulatory legislation and other relevant material through the 102d Congress, 2d Session. This compilation has been prepared for use as a resource document, which the NRC intends to update at the end of every Congress. The contents of NUREG-0980 include: The Atomic Energy Act of 1954, as amended; Energy Reorganization Act of 1974, as amended, Uranium Mill Tailings Radiation Control Act of 1978; Low-Level Radioactive Waste Policy Act; Nuclear Waste Policy Act of 1982; and NRC Authorization and Appropriations Acts. Other materials included are statutes and treaties on export licensing, nuclear non-proliferation, andmore » environmental protection.« less

Nuclear regulatory legislation, 102d Congress. Volume 2, No. 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-10-01

This document is a compilation of nuclear regulatory legislation and other relevant material through the 102d Congress, 2d Session. This compilation has been prepared for use as a resource document, which the NRC intends to update at the end of every Congress. The contents of NUREG-0980 include The Atomic Energy Act of 1954, as amended; Energy Reorganization Act of 1974, as amended, Uranium Mill Tailings Radiation Control Act of 1978; Low-Level Radioactive Waste Policy Act; Nuclear Waste Policy Act of 1982; and NRC Authorization and Appropriations Acts. Other materials included are statutes and treaties on export licensing, nuclear non-proliferation, andmore » environmental protection.« less

Communication: Adiabatic and non-adiabatic electron-nuclear motion: Quantum and classical dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert, Julian; Kaiser, Dustin; Engel, Volker

2016-05-07

Using a model for coupled electronic-nuclear motion we investigate the range from negligible to strong non-adiabatic coupling. In the adiabatic case, the quantum dynamics proceeds in a single electronic state, whereas for strong coupling a complete transition between two adiabatic electronic states takes place. It is shown that in all coupling regimes the short-time wave-packet dynamics can be described using ensembles of classical trajectories in the phase space spanned by electronic and nuclear degrees of freedom. We thus provide an example which documents that the quantum concept of non-adiabatic transitions is not necessarily needed if electronic and nuclear motion ismore » treated on the same footing.« less

Ubiquitin‑like protein FAT10 regulates DNA damage repair via modification of proliferating cell nuclear antigen.

PubMed

Chen, Zhenchuan; Zhang, Wei; Yun, Zhimin; Zhang, Xue; Gong, Feng; Wang, Yunfang; Ji, Shouping; Leng, Ling

2018-06-01

In response to DNA damage, proliferating cell nuclear antigen (PCNA) has an important role as a positive regulator and as a scaffold protein associated with DNA damage bypass and repair pathways by serving as a platform for the recruitment of associated components. As demonstrated in the present study, the ubiquitin‑like modifier human leukocyte antigen F locus adjacent transcript 10 (FAT10), which binds to PCNA but has not previously been demonstrated to be associated with the DNA damage response (DDR), is induced by ultraviolet/ionizing radiation and VP‑16 treatment in HeLa cells. Furthermore, DNA damage enhances FAT10 expression. Immunoprecipitation analysis suggested PCNA is modified by FAT10, and the degradation of FATylated PCNA located in the cytoplasm is regulated by the 26S proteasome, which is also responsible for the upregulation of nuclear foci formation. Furthermore, immunofluorescence experiment suggested FAT10 co‑localizes with PCNA in nuclear foci, thus suggesting that FATylation of PCNA may affect DDR via the induction of PCNA degradation in the cytoplasm or nucleus. In addition, immunohistochemistry experiment suggested the expression levels of FAT10 and PCNA are enhanced in HCC tissues compared with healthy liver tissues; however, the expression of FAT10 is suppressed in regenerated liver tissues, which express high levels of PCNA, thus suggesting that the association between FAT10 and PCNA expression is only exhibited in tumor tissues. In conclusion, the results of the present study suggest that FAT10 may be involved in DDR and therefore the progression of tumorigenesis.

Regulation of Proteome Maintenance Gene Expression by Activators of Peroxisome Proliferator-Activated Receptor a (PPARa)

EPA Science Inventory

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa) is activated by a large number of xenobiotic and hypolipidemic compounds called peroxisome proliferator chemicals (PPC). One agonist of PPARa (WY-14,643) regulates responses in the mouse liver to chemic...

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

PubMed

Zhang, Chao; Lu, Jing; Zhang, Quan-Wu; Zhao, Wei; Guo, Jia-Hui; Liu, Shan-Ling; Wu, Ying-Li; Jiang, Bin; Gao, Feng-Hou

2016-10-01

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of High Fidelity, Fuel-Like Thermal Simulators for Non-Nuclear Testing

NASA Technical Reports Server (NTRS)

Bragg-Sitton, S. M.; Farmer, J.; Dixon, D.; Kapernick, R.; Dickens, R.; Adams, M.

2007-01-01

Non-nuclear testing can be a valuable tool in development of a space nuclear power or propulsion system. In a non-nuclear test bed, electric heaters are used to simulate the heat from nuclear fuel. Work at the NASA Marshall Space Flight Center seeks to develop high fidelity thermal simulators that not only match the static power profile that would be observed in an operating, fueled nuclear reactor, but to also match the dynamic fuel pin performance during feasible transients. Comparison between the fuel pins and thermal simulators is made at the fuel clad surface, which corresponds to the sheath surface in the thermal simulator. Static and dynamic fuel pin performance was determined using SINDA-FLUINT analysis, and the performance of conceptual thermal simulator designs was compared to the expected nuclear performance. Through a series of iterative analysis, a conceptual high fidelity design will be developed, followed by engineering design, fabrication, and testing to validate the overall design process. Although the resulting thermal simulator will be designed for a specific reactor concept, establishing this rigorous design process will assist in streamlining the thermal simulator development for other reactor concepts.

PRIC320, a transcription coactivator, isolated from peroxisome proliferator-binding protein complex.

PubMed

Surapureddi, Sailesh; Viswakarma, Navin; Yu, Songtao; Guo, Dongsheng; Rao, M Sambasiva; Reddy, Janardan K

2006-05-05

Ciprofibrate, a potent peroxisome proliferator, induces pleiotropic responses in liver by activating peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor. Transcriptional regulation by liganded nuclear receptors involves the participation of coregulators that form multiprotein complexes possibly to achieve cell and gene specific transcription. SDS-PAGE and matrix-assisted laser desorption/ionization reflection time-of-flight mass spectrometric analyses of ciprofibrate-binding proteins from liver nuclear extracts obtained using ciprofibrate-Sepharose affinity matrix resulted in the identification of a new high molecular weight nuclear receptor coactivator, which we designated PRIC320. The full-length human cDNA encoding this protein has an open-reading frame that codes for a 320kDa protein containing 2882 amino acids. PRIC320 contains five LXXLL signature motifs that mediate interaction with nuclear receptors. PRIC320 binds avidly to nuclear receptors PPARalpha, CAR, ERalpha, and RXR, but only minimally with PPARgamma. PRIC320 also interacts with transcription cofactors CBP, PRIP, and PBP. Immunoprecipitation-immunoblotting as well as cellular localization studies confirmed the interaction between PPARalpha and PRIC320. PRIC320 acts as a transcription coactivator by stimulating PPARalpha-mediated transcription. We conclude that ciprofibrate, a PPARalpha ligand, binds a multiprotein complex and PRIC320 cloned from this complex functions as a nuclear receptor coactivator.

Explaining weapons proliferation: Going beyond the security dilemma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rattray, G.J.

1994-07-01

Most analyses addressing the subject of why states choose to proliferate focus on external motivations, particularly the security dilemma, facing a country`s leaders. This paper concludes that, other factors, such as prestige, regime type and stability, and economic status, can have impact in determining proliferation outcomes. In the case of Newly Independent States of the former Soviet Union (NIS), the domestic problems generated by internal conflicts, arms remaining from the Cold War, excess defense industrial capacity, economic difficulties and the breakdown of central authority resulting in a loss of border control and corruption have all made the NIS an extremelymore » fertile ground for weapons proliferation. A more positive `rollback` situation has emerged in Latin America where both Argentina and Brazil have seemingly decided to forgo the acquisition of nuclear weapons and ballistic missiles. The US must understand the `strategic personality` of each potential proliferation. Not all state behavior can be explained in terms of the security dilemma. One must also keep in mind the complexity of possible motivations. Economic and technological assistance and cooperative efforts at institution-building hold great potential to combating proliferation.« less

Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells through the Toll-like receptor 4/nuclear factor-κB pathway.

PubMed

Jiang, Ninghong; Xie, Feng; Guo, Qisang; Li, Ming-Qing; Xiao, Jingjing; Sui, Long

2017-06-01

Toll-like receptor 4 is overexpressed in various tumors, including cervical carcinoma. However, the role of Toll-like receptor 4 in cervical cancer remains controversial, and the underlying mechanisms are largely elusive. Therefore, Toll-like receptor 4 in cervical cancer and related mechanisms were investigated in this study. Quantitative reverse transcription polymerase chain reaction and western blot analyses were used to detect messenger RNA and protein levels in HeLa, Caski, and C33A cells with different treatments. Proliferation was quantified using Cell Counting Kit-8. Cell cycle distribution and apoptosis were assessed by flow cytometry. Higher levels of Toll-like receptor 4 expression were found in human papillomavirus-positive cells compared to human papillomavirus-negative cells. Proliferation of HeLa and Caski cells was promoted in lipopolysaccharide-stimulated groups but suppressed in short hairpin RNA-transfected groups. Apoptosis rates were lower in lipopolysaccharide-stimulated groups relative to short hairpin RNA-transfected groups. In addition, G2-phase distribution was enhanced when Toll-like receptor 4 was downregulated. Moreover, the pNF-κBp65 level was positively correlated with the Toll-like receptor 4 level in HeLa and Caski cells, though when an nuclear factor-κB inhibitor was applied to lipopolysaccharide-stimulated groups, the patterns of proliferation and apoptosis were opposite to those of the lipopolysaccharide-stimulated groups without inhibitor treatment. In conclusion, these data suggest that Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells at least in part through the Toll-like receptor 4/nuclear factor-κB pathway, which may be correlated with the occurrence and development of cervical carcinoma.

Nuclear Proliferation: A Unit for Study.

ERIC Educational Resources Information Center

Fernekes, William R.

1990-01-01

Using Argentina as a sample case study, presents a classroom unit designed to explain the implications for world peace of nuclear weapons development. Employs a policy analysis model to make an indepth examination of the values underlying all government policy decisions. Includes unit topics and procedures for the exercise. (NL)

Meeting Summary of Kitchen Cabinet on Financial Due Diligence to Reduce Proliferation Risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hund, Gretchen; Weise, Rachel A.; Carr, Geoffrey A.

The U.S. Department of Energy’s Pacific Northwest National Laboratory convened the Kitchen Cabinet (KC) to facilitate a candid discussion about the role of financial institutions (FIs) in antiproliferation efforts to reduce nuclear proliferation risks by identifying suspicious business transactions and exports when making lending or insurance decisions. The meeting brought together a group of export control specialists, largely representatives from the Nuclear Suppliers Group (NSG) Participating Governments (PGs) and finance experts representing banks and insurance companies. By assembling a KC of experts, the group could understand what suspicious transactions look like from each other’s perspectives and better inform each ofmore » their operations. The goal was to develop red flags FIs could use to identify suspicious proliferation-related transactions and to help governments gain a clearer picture of proliferation using financial information.« less

Panel session on "safety, health and the environment: implications of nuclear power growth".

PubMed

Bilbao y León, Sama

2011-01-01

This paper summarizes the presentations and the insights offered by panelists John P. Winston, Robert Bernero, and Stephen LaMontagne during the Panel on Safety, Health and the Environment: Implications of Nuclear Power Growth that took place during the NCRP 2009 Annual Meeting. The paper describes the opportunities and the challenges faced in the areas of infrastructure development, radiation control, licensing and regulatory issues, and non-proliferation as a consequence of the forecasted growth in nuclear power capacity worldwide. Copyright © 2010 Health Physics Society

Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma.

PubMed

Ram, Babul Moni; Dolpady, Jayashree; Kulkarni, Rakesh; Usha, R; Bhoria, Usha; Poli, Usha Rani; Islam, Mojahidul; Trehanpati, Nirupma; Ramakrishna, Gayatri

2018-01-01

The calcineurin-NFAT signaling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signaling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity. The nuclear levels of both NFAT1 and NFAT3 remain unaltered implicating they have little role in cervical carcinogenesis. Similar to the in vitro studies, the HPV infected human squamous cell carcinoma specimens showed higher NFAT2 levels compared to the normal cervical epithelium. Depletion of NFAT2 by RNAi attenuated growth of SiHa cells. Overexpression of HPV16 oncoproteins viz, E6 and E7 increased NFAT2 expression levels and DNA binding activity, while knockdown of E6 by RNAi decreased the same. Briefly, we now report an activation of calcineurin-NFAT2 axis in cervical cancer and a novel role of HPV oncoprotein in facilitating NFAT2 dependent cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development.

PubMed

Ames, Kristina; Da Cunha, Dayse S; Gonzalez, Brenda; Konta, Marina; Lin, Feng; Shechter, Gabriel; Starikov, Lev; Wong, Sara; Bülow, Hannes E; Meléndez, Alicia

2017-03-20

The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16.2/ATG16L, atg-18/WIPI1/2, and atg-7/ATG7 are required for the late larval expansion of germline stem cell progenitors in the C. elegans gonad. We further show that BEC-1/BECN1/Beclin1 acts independently of the GLP-1/Notch or DAF-7/TGF-β pathways but together with the DAF-2/insulin IGF-1 receptor (IIR) signaling pathway to promote germline stem cell proliferation. Similar to DAF-2/IIR, BEC-1/BECN1/Beclin1, ATG-18/WIPI1/2, and ATG-16.2/ATG16L all promote cell-cycle progression and are negatively regulated by the phosphatase and tensin homolog DAF-18/PTEN. However, whereas BEC-1/BECN1/Beclin1 acts through the transcriptional regulator SKN-1/Nrf1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L exert their function through the DAF-16/FOXO transcription factor. In contrast, ATG-7 functions in concert with the DAF-7/TGF-β pathway to promote germline proliferation and is not required for cell-cycle progression. Finally, we report that BEC-1/BECN1/Beclin1 functions non-cell-autonomously to facilitate cell-cycle progression and stem cell proliferation. Our findings demonstrate a novel non-autonomous role for BEC-1/BECN1/Beclin1 in the control of stem cell proliferation and cell-cycle progression, which may have implications for the understanding and development of therapies against malignant cell growth in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells.

PubMed

Maillard, Virginie; Desmarchais, Alice; Durcin, Maeva; Uzbekova, Svetlana; Elis, Sebastien

2018-04-26

Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid (PUFA) belonging to a family of biologically active fatty acids (FA), which are known to have numerous health benefits. N-3 PUFAs affect reproduction in cattle, and notably directly affect follicular cells. In terms of reproduction in cattle, n-3 PUFA-enriched diets lead to increased follicle size or numbers. The objective of the present study was to analyze the effects of DHA (1, 10, 20 and 50 μM) on proliferation and steroidogenesis (parametric and/or non parametric (permutational) ANOVA) of bovine granulosa cells in vitro and mechanisms of action through protein expression (Kruskal-Wallis) and signaling pathways (non parametric ANOVA) and to investigate whether DHA could exert part of its action through the free fatty acid receptor 4 (FFAR4). DHA (10 and 50 μM) increased granulosa cell proliferation and DHA 10 μM led to a corresponding increase in proliferating cell nuclear antigen (PCNA) expression level. DHA also increased progesterone secretion at 1, 20 and 50 μM, and estradiol secretion at 1, 10 and 20 μM. Consistent increases in protein levels were also reported for the steroidogenic enzymes, cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), and of the cholesterol transporter steroidogenic acute regulatory protein (StAR), which are necessary for production of progesterone or androstenedione. FFAR4 was expressed in all cellular types of bovine ovarian follicles, and in granulosa cells it was localized close to the cellular membrane. TUG-891 treatment (1 and 50 μM), a FFAR4 agonist, increased granulosa cell proliferation and MAPK14 phosphorylation in a similar way to that observed with DHA treatment. However, TUG-891 treatment (1, 10 and 50 μM) showed no effect on progesterone or estradiol secretion. These data show that DHA stimulated proliferation and steroidogenesis of bovine

Developments in Assisting Countries in Implementing the IAEA Additional Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Killinger, Mark H.; Hansen, Linda H.; Cain, Ronald A.

In 2008, the U.S. Department of Energy (DOE) began assisting selected non-nuclear weapon states in planning and preparing for implementation of the International Atomic Energy Agency’s Additional Protocol (AP). Since then, the AP international implementation program has contributed to the substantial progress made by Vietnam, Thailand, Iraq, and Malaysia in preparing for entry-into-force of the AP. An overall engagement plan has been developed with components designed to train government AP implementing agencies, inform policy makers, conduct outreach to industry and universities, make AP reporting software available and useful, and plan a detailed approach for implementing the declaration and complementary accessmore » provisions of the AP. DOE recently began collaborating with Indonesia, which has already entered the AP into force, requiring a second method of engagement somewhat different from that taken with countries that have not entered the AP into force. The AP international implementation program, administered by the International Nuclear Safeguards and Engagement Program, is working more closely with DOE’s International Nonproliferation Export Control Program to ensure countries are aware of and prepared to implement the export/import provisions of the AP. As the AP implementation program matures and helps move countries closer to entry-into-force or improved AP implementation, it is identifying characteristics of a country’s “end-state” that indicate that DOE assistance is no longer required. The U.S. AP Implementation Act and Senate Resolution of Ratification require the Administration to report annually to Congress on measures taken to achieve the adoption of the AP in non-nuclear weapon states. DOE’s AP international implementation program is a significant part of these measures. This paper describes recent developments to increase the scope and effectiveness of the program.« less

Molecular targets and signaling pathways regulated by nuclear translocation of syndecan-1.

PubMed

Szatmári, Tünde; Mundt, Filip; Kumar-Singh, Ashish; Möbus, Lena; Ötvös, Rita; Hjerpe, Anders; Dobra, Katalin

2017-12-08

The cell-surface heparan sulfate proteoglycan syndecan-1 is important for tumor cell proliferation, migration, and cell cycle regulation in a broad spectrum of malignancies. Syndecan-1, however, also translocates to the cell nucleus, where it might regulate various molecular functions. We used a fibrosarcoma model to dissect the functions of syndecan-1 related to the nucleus and separate them from functions related to the cell-surface. Nuclear translocation of syndecan-1 hampered the proliferation of fibrosarcoma cells compared to the mutant lacking nuclear localization signal. The growth inhibitory effect of nuclear syndecan-1 was accompanied by significant accumulation of cells in the G0/G1 phase, which indicated a possible G1/S phase arrest. We implemented multiple, unsupervised global transcriptome and proteome profiling approaches and combined them with functional assays to disclose the molecular mechanisms that governed nuclear translocation and its related functions. We identified genes and pathways related to the nuclear compartment with network enrichment analysis of the transcriptome and proteome. The TGF-β pathway was activated by nuclear syndecan-1, and three genes were significantly altered with the deletion of nuclear localization signal: EGR-1 (early growth response 1), NEK11 (never-in-mitosis gene a-related kinase 11), and DOCK8 (dedicator of cytokinesis 8). These candidate genes were coupled to growth and cell-cycle regulation. Nuclear translocation of syndecan-1 influenced the activity of several other transcription factors, including E2F, NFκβ, and OCT-1. The transcripts and proteins affected by syndecan-1 showed a striking overlap in their corresponding biological processes. These processes were dominated by protein phosphorylation and post-translation modifications, indicative of alterations in intracellular signaling. In addition, we identified molecules involved in the known functions of syndecan-1, including extracellular matrix

UV fluorescence excitation spectroscopy as a non-invasive predictor of epidermal proliferation and clinical performance of cosmetic formulations

NASA Astrophysics Data System (ADS)

Maidhof, Robert; Liebel, Frank; Hwang, Cheng; Ruvolo, Eduardo; Lyga, John

2017-02-01

The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). These cells are continually shed from the outside and replaced from the inside in a process called desquamation which is controlled by two biological events - proliferation and differentiation. One method to non-invasively study biological changes in the skin is using fluorescence excitation spectroscopy. Several characteristic excitation-emission peaks occur in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in skin proliferation, cell turnover, epidermal thickening, and skin aging. We hypothesize that changes in this fluorescent signal could be used to assess the potential activity of cosmetic anti-aging compounds to deliver a benefit to skin. Previous work with retinol and glycolic acid, two commonly used actives that effect epidermal proliferation and exfoliation, has demonstrated an increase in F295 (attributed to tryptophan excitation fluorescence). In this study we present the results of a placebo controlled study that aims to correlate changes in F295 with biological performance (epidermal thickening and Ki67 expression).

Experience in implementation of «Nuclear Knowledge Management» course at the National Research Nuclear University MEPhI

NASA Astrophysics Data System (ADS)

Geraskin, N. I.; Kosilov, A. N.

2017-01-01

This paper describes the experience of teaching «Nuclear Knowledge Management» course at the National Research Nuclear University MEPhI (NRNU MEPhI). Currently, the course is implemented both in engineer and master degree programs and is attended by over 50 students. Goal, objectives and syllabus of the course are discussed in detail. A special attention is paid to practical exercises and final examination options in the case of small and large student groups. The course is supported by the Cyber Learning Platform for Nuclear Education and Training (CLP4NET), developed by the IAEA. The experience of NRNU MEPhI lecturers assisting in conducting the International School of Nuclear Knowledge Management, held annually in Trieste (Italy), is described with a special attention to the fact, that the course has passed the certification process at Academic Council of NRNU MEPhI. In 2014 and 2015 the course has been recognized as one of the best ones in NRNU MEPhI. Finally, perspectives of «Nuclear Knowledge Management» course are considered. They include increase of the course duration, introduction of the course into the learning process of other departments and institutions of the university, and transferring the course to other members of the Association «Consortium of ROSATOM supporting universities».

Localization of peroxisome proliferator-activated receptor in mouse and rat-tissues and demonstration of its nuclear translocation in transfected cv-1 cells.

PubMed

Huang, Q; Yeldandi, A; Alvares, K; Ide, H; Reddy, J; Rao, M

1995-02-01

Hepatocarcinogenesis in rodents induced by nongenotoxic peroxisome proliferators is postulated to be a receptor-mediated process. The peroxisome proliferator-activated receptors (PPAR) are members of the steroid hormone receptor superfamily, which participate in ligand-dependent transcriptional activation of peroxisomal fatty acid beta oxidation enzyme system genes in liver parenchymal cells of rats and mice. In order to study the tissue distribution and cellular localization of PPAR, we raised polyclonal antibodies against PPAR using a recombinant rat PPAR (rPPAR) expressed as a glutathione-S-transferase-rPPAR fusion protein. On immunoblot analysis the antibodies specifically recognized a 55 kDa PPAR protein in rat, mouse and human liver homogenates. Immunoblotting also showed that in the mouse and rat, PPAR is expressed in liver, kidney and heart, and only weakly in brain and testis. Immunohistochemical localization in the rat and mouse revealed that PPAR is highly expressed in perivenular (i.e., those surrounding hepatic vein) hepatocytes and very weakly in the cytoplasm of remaining hepatocytes. In the kidney, PPAR was visualized predominantly in the p(3) segments of proximal convoluted tubular epithelium. CV-1 cells transiently transfected with rPPAR cDNA construct showed predominant cytoplasmic fluorescence; treatment of these cells with ciprofibrate, a peroxisome proliferator, resulted in the nuclear translocation of PPAR signal.

P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Pengfei; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; Gao, Shen

2014-07-18

Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanismmore » by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lung tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.« less

Fascin Overexpression Promotes Cholangiocarcinoma RBE Cell Proliferation, Migration, and Invasion.

PubMed

Zhao, Haiying; Yang, Fuquan; Zhao, Wenyan; Zhang, Chunjv; Liu, Jingang

2016-04-01

Fascin is overexpressed in various tumor tissues and is closely related to tumor metastasis and invasion. However, the role of fascin in cholangiocarcinoma RBE cells has not been clearly reported. This study aimed to establish a cholangiocarcinoma cell line with stable and high expression of fascin to observe the effect of fascin on cell proliferation, migration, and invasion. A fascin overexpression vector, pcDNA3.1-Fascin, was constructed and transfected into the human cholangiocarcinoma RBE cell line. The results of real-time polymerase chain reaction, Western blot, and immunofluorescence indicated that fascin was steadily and highly expressed in RBE cells. The results of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and colony formation assay indicated that upregulated fascin expression could enhance cholangiocarcinoma cell proliferation. The results of wound healing assay and transwell assay indicated that fascin could promote cholangiocarcinoma cell migration and invasion, and a further study found that the nuclear factor-κB signaling pathway was activated after upregulation of fascin, whereas E-cadherin expression in these cells was significantly decreased. Additionally, E-cadherin expression was significantly increased after inhibiting nuclear factor-κB activity using inhibitor or small interfering RNA, and E-cadherin expression was decreased by fascin overexpression after nuclear factor-κB inhibition, suggesting that nuclear factor-κB signaling pathway was not involved in the regulation of E-cadherin by fascin. In summary, the results of this study demonstrated that fascin effectively promoted cholangiocarcinoma RBE cell proliferation, migration, and invasion. This study provides evidence for fascin as a potential target in the treatment of cholangiocarcinoma. © The Author(s) 2015.

miR-342-3p affects hepatocellular carcinoma cell proliferation via regulating NF-κB pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Liang; Zhang, Yubao, E-mail: zhyb880077@sina.com

2015-02-13

Recent research indicates that non-coding microRNAs (miRNAs) help regulate basic cellular processes in many types of cancer cells. We hypothesized that overexpression of miR-342-3p might affect proliferation of hepatocellular carcinoma (HCC) cells. After confirming overexpression of miR-342-3p with qRT-PCR, MTT assay showed that HCC cell proliferation was significantly inhibited by miR-342-3p, and that it significantly decreased BrdU-positive cell proliferation by nearly sixfold. Searching for targets using three algorithms we found that miR-342-3p is related to the NF-κB pathway and luciferase assay found that IKK-γ, TAB2 and TAB3 are miR-342-3p target genes. Results of western blot on extracted nuclear proteins ofmore » HepG2 and HCT-116 cells showed that miR-342-3p reduced and miR-342-3p-in increased p65 nuclear levels and qRT-PCR found that NF-κB pathway downstream genes were downregulated by miR-342-3p and upregulated by miR-342-3p-in, confirming that miR-342 targets NF-κB pathway. Overexpression of Ikk-γ, TAB2 and TAB3 partially rescued HCC cells proliferation inhibited by miR-342-3p. Using the GSE54751 database we evaluated expression from 10 HCC samples, which strongly suggested downregulation of miR-342-3p and we also found inverse expression between miR-342-3p and its targets IKK-γ, TAB2 and TAB3 from 71 HCC samples. Our results show that miR-342-3p has a significant role in HCC cell proliferation and is suitable for investigation of therapeutic targets. - Highlights: • MiR-342-3p suppresses hepatocellular carcinoma cell proliferation. • MiR-342-3p targets IKK-γ, TAB2 and TAB3 genes. • MiR-342-3p downregulates NF-kB signaling pathway. • MiR-342-3p is downregulated in clinical hepatocellular carcinoma samples. • The expression of miR-342-3p and its target gene is inversely related.« less

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2010-02-04

Terrorism in Pakistan: Sabotage of a Spent Fuel Cask or a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008; Martellini, 2008...measures to prevent unauthorized or accidental use of nuclear weapons, as well as contribute to physical security of storage facilities and personnel...strategic nuclear assets could be obtained by terrorists, or used by elements in the Pakistani government. Chair of the Joint Chiefs of Staff Admiral

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2009-07-30

Pakistan: Sabotage of a Spent Fuel Cask or a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008; Martellini, 2008. 79...that Pakistan’s strategic nuclear assets could be obtained by terrorists, or used by elements in the Pakistani government. Chair of the Joint Chiefs...that gave additional urgency to the program. Pakistan produced fissile material for its nuclear weapons using gas-centrifuge-based uranium

Pakistan’s Nuclear Weapons: Proliferation and Security Issues

DTIC Science & Technology

2010-10-07

Pakistan: Sabotage of a Spent Fuel Cask or a Commercial Irradiation Source in Transport ,” in Pakistan’s Nuclear Future, 2008; Martellini, 2008. 99...prevent unauthorized or accidental use of nuclear weapons, as well as contribute to physical security of storage facilities and personnel reliability... nuclear assets could be obtained by terrorists, or used by elements in the Pakistani government. Chair of the Joint Chiefs of Staff Admiral Michael

Off-Site Monitoring of Nuclear Fuel Reprocessing Plants for Nuclear Weapons Proliferation

DTIC Science & Technology

1980-01-01

of commercial nuclear power reactors by the collection of cesium and neodynium radionuclides and the use-of isotopic correlation techniques.Both...Both Goodwin (ref 1) and Clark (ref 2) investigated off-site monitoring of commercial nuclear power reactoze by the collection of cesium and neodynium...manner than that which is used for power production.Economical generation of electrical power requires a long sus- tained fission cycle whereas Pu-239

A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation and fibre differentiation.

PubMed

Dawes, L J; Shelley, E J; McAvoy, J W; Lovicu, F J

2018-04-01

Recent studies indicate an important role for the transcriptional co-activator Yes-associated protein (YAP), and its regulatory pathway Hippo, in controlling cell growth and fate during lens development; however, the exogenous factors that promote this pathway are yet to be identified. Given that fibroblast growth factor (FGF)-signaling is an established regulator of lens cell behavior, the current study investigates the relationship between this pathway and Hippo/YAP-signaling during lens cell proliferation and fibre differentiation. Rat lens epithelial explants were cultured with FGF2 to induce epithelial cell proliferation or fibre differentiation. Immunolabeling methods were used to detect the expression of Hippo-signaling components, Total and Phosphorylated YAP, as well as fibre cell markers, Prox-1 and β-crystallin. FGF-induced lens cell proliferation was associated with a strong nuclear localisation of Total-YAP and low-level immuno-staining for phosphorylated-YAP. FGF-induced lens fibre differentiation was associated with a significant increase in cytoplasmic phosphorylated YAP (inactive state) and enhanced expression of core Hippo-signaling components. Inhibition of YAP with Verteporfin suppressed FGF-induced lens cell proliferation and ablated cell elongation during lens fibre differentiation. Inhibition of either FGFR- or MEK/ERK-signaling suppressed FGF-promoted YAP nuclear translocation. Here we propose that FGF promotes Hippo/YAP-signaling during lens cell proliferation and differentiation, with FGF-induced nuclear-YAP expression playing an essential role in promoting the proliferation of lens epithelial cells. An FGF-induced switch from proliferation to differentiation, hence regulation of lens growth, may play a key role in mediating Hippo suppression of YAP transcriptional activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of open source information and commercial satellite imagery for nuclear nonproliferation regime compliance verification by a community of academics

NASA Astrophysics Data System (ADS)

Solodov, Alexander

The proliferation of nuclear weapons is a great threat to world peace and stability. The question of strengthening the nonproliferation regime has been open for a long period of time. In 1997 the International Atomic Energy Agency (IAEA) Board of Governors (BOG) adopted the Additional Safeguards Protocol. The purpose of the protocol is to enhance the IAEA's ability to detect undeclared production of fissile materials in member states. However, the IAEA does not always have sufficient human and financial resources to accomplish this task. Developed here is a concept for making use of human and technical resources available in academia that could be used to enhance the IAEA's mission. The objective of this research was to study the feasibility of an academic community using commercially or publicly available sources of information and products for the purpose of detecting covert facilities and activities intended for the unlawful acquisition of fissile materials or production of nuclear weapons. In this study, the availability and use of commercial satellite imagery systems, commercial computer codes for satellite imagery analysis, Comprehensive Test Ban Treaty (CTBT) verification International Monitoring System (IMS), publicly available information sources such as watchdog groups and press reports, and Customs Services information were explored. A system for integrating these data sources to form conclusions was also developed. The results proved that publicly and commercially available sources of information and data analysis can be a powerful tool in tracking violations in the international nuclear nonproliferation regime and a framework for implementing these tools in academic community was developed. As a result of this study a formation of an International Nonproliferation Monitoring Academic Community (INMAC) is proposed. This would be an independent organization consisting of academics (faculty, staff and students) from both nuclear weapon states (NWS) and

Command and Control in New Nuclear States: Implications for Stability

DTIC Science & Technology

1994-06-01

dangerous" scenario being one of nuclear proliferation "well- managed by the current nuclear powers."’’ Inside of Mearsheimer’s paradigm for peace and...expanded (but managed ) nuclear proliferation would tend to equalize military power amoung states and thus bolster stratigic stability generally. B...31Ashton B. Carter, John D. Steinbruner and Charles A. Zraket, ed., Managing Nuclear Orerations, (Washington, DC: Brookings,1987), 1. 32Webster’s New

An introduction to implementation science for the non-specialist.

PubMed

Bauer, Mark S; Damschroder, Laura; Hagedorn, Hildi; Smith, Jeffrey; Kilbourne, Amy M

2015-09-16

The movement of evidence-based practices (EBPs) into routine clinical usage is not spontaneous, but requires focused efforts. The field of implementation science has developed to facilitate the spread of EBPs, including both psychosocial and medical interventions for mental and physical health concerns. The authors aim to introduce implementation science principles to non-specialist investigators, administrators, and policymakers seeking to become familiar with this emerging field. This introduction is based on published literature and the authors' experience as researchers in the field, as well as extensive service as implementation science grant reviewers. Implementation science is "the scientific study of methods to promote the systematic uptake of research findings and other EBPs into routine practice, and, hence, to improve the quality and effectiveness of health services." Implementation science is distinct from, but shares characteristics with, both quality improvement and dissemination methods. Implementation studies can be either assess naturalistic variability or measure change in response to planned intervention. Implementation studies typically employ mixed quantitative-qualitative designs, identifying factors that impact uptake across multiple levels, including patient, provider, clinic, facility, organization, and often the broader community and policy environment. Accordingly, implementation science requires a solid grounding in theory and the involvement of trans-disciplinary research teams. The business case for implementation science is clear: As healthcare systems work under increasingly dynamic and resource-constrained conditions, evidence-based strategies are essential in order to ensure that research investments maximize healthcare value and improve public health. Implementation science plays a critical role in supporting these efforts.

The Inadvertent Effect of Assurance on Nuclear Proliferation

DTIC Science & Technology

2013-02-14

those of the author and do not reflect the official policy or position of the US government, the Department of Defense, or Air University. In...umbrella and a state’s normative desire to be viewed and treated favorably by the international community dissuades nuclear weapons development.2...desire to be viewed and treated favorably by the international community dissuades nuclear weapons development.24 Tatsumi and Schoff suggest the best

The role of nuclear energy in mitigating greenhouse warming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krakowski, R.A.

1997-12-31

A behavioral, top-down, forced-equilibrium market model of long-term ({approximately} 2,100) global energy-economics interactions has been modified with a bottom-up nuclear energy model and used to construct consistent scenarios describing future impacts of civil nuclear materials flows in an expanding, multi-regional (13) world economy. The relative measures and tradeoffs between economic (GNP, tax impacts, productivity, etc.), environmental (greenhouse gas accumulations, waste accumulation, proliferation risk), and energy (resources, energy mixes, supply-side versus demand-side attributes) interactions that emerge from these analyses are focused herein on advancing understanding of the role that nuclear energy (and other non-carbon energy sources) might play in mitigating greenhousemore » warming. Two ostensibly opposing scenario drivers are investigated: (a) demand-side improvements in (non-price-induced) autonomous energy efficiency improvements; and (b) supply-side carbon-tax inducements to shift energy mixes towards reduced- or non-carbon forms. In terms of stemming greenhouse warming for minimal cost of greenhouse-gas abatement, and with the limitations of the simplified taxing schedule used, a symbiotic combination of these two approaches may offer advantages not found if each is applied separately.« less

Influence of long-term, high-dose dexamethasone administration on proliferation and apoptosis in porcine hepatocytes.

PubMed

Mikiewicz, Mateusz; Otrocka-Domagała, Iwona; Paździor-Czapula, Katarzyna; Rotkiewicz, Tadeusz

2017-06-01

The aim of this study was to examine the influence of long-term, high-dose dexamethasone administration on the liver, with particular emphasis on hepatocyte proliferation and apoptosis, using a swine model. The study included 48 large, female Polish breed pigs aged 3months (weighing ca. 30kg) divided into groups I (control; n=24) and II (dexamethasone; n=24) that receiving intra-muscular injections of monosodium phosphate dexamethasone for 29days. The pigs were euthanized on days subsequent to the experiment. Immediately after the euthanasia, the pig livers were sampled, fixed, and processed routinely for histopathology, histochemistry, and immunohistochemistry (for proliferating cell nuclear antigen, Bcl-2, and caspase-3). Apoptosis was visualized by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL). Dexamethasone administration gradually caused hepatocyte glycogen degeneration and finally lipid degeneration, accompanied by sinusoid and central vein dilatation and nuclear chromatin condensation. The proliferating cell nuclear antigen index, mean number of argyrophilic nucleolar organizer regions and proliferation index of argyrophilic nucleolar organizer regions were lower, while Bcl-2 expression was higher in group II compared with group I. The results from this study suggest that safe high-dose dexamethasone administration time is difficult to establish. Long-term, high-dose dexamethasone administration can cause pronounced morphological changes in hepatocytes by diminishing their transcriptional and proliferation activity but also protects them from apoptosis by potentially affecting Bcl-2 expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overexpression of ZIC5 promotes proliferation in non-small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Qi; Shi, Run; Wang, Xin

Background: Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths. It is therefore urgent that we identify new molecular targets to help cure NSCLC patients. Here, we identified ZIC5 as a potential novel oncogene. Methods: We detected the expression of ZIC5 in tumor and normal tissues of NSCLC patients using quantitative real-time PCR and explored its clinical appearance. We then knocked down ZIC5 to observe changes in NSCLC cell proliferation and metastasis. Nude mouse xenograft models were established to measure ZIC5's function in vivo. Results: Our results revealed that ZIC5 was expressed at dramatically higher levels inmore » NSCLC tumor tissues than in normal tissues. High levels of ZIC5 expression were associated with a higher primary tumor grade. ZIC5 expression was significantly inhibited by small interfering RNA. After silencing ZIC5, the metastatic capacity of NSCLC cells was clearly lower. Knocking down ZIC5 significantly inhibited the proliferation of NSCLC cells, causing the cell cycle to be arrested in G2 phase. Xenograft tumor models showed that knocking down ZIC5 also inhibited tumor growth in vivo. Q-PCR and western blot analysis revealed that ZIC5 expression was closely associated with CCNB1 and CDK1 complex expression, while other cell cycle-related genes showed no significant correlation with ZIC5. Conclusions: Our experiment show that ZIC5 is highly upregulated in NSCLC tumor tissues and suggest that ZIC5 may act as an oncogene by influencing CCNB1 and CDK1 complex expression. ZIC5 may therefore be a potential biomarker and therapeutic target for NSCLC patients.« less

Overview of nuclear energy: Present and projected use

NASA Astrophysics Data System (ADS)

Stanculescu, Alexander

2012-06-01

Several factors will influence the contribution of nuclear energy to the future energy mix. Among them, the most important are the degree of global commitment to greenhouse gas reduction, continued vigilance in safety and safeguards, technological advances, economic competitiveness and innovative financing arrangements for new nuclear power plant constructions, the implementation of nuclear waste disposal, and, last but not least, public perception, information and education. The paper presents an overview of the current nuclear energy situation, possible development scenarios, of reactor technology, and of non-electric applications of nuclear energy.

Implementation and Sustainability of the Russian Federation Ministry of Defense Nuclear Personnel Reliability Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

LataPhD, Vasiliy; Coates, Cameron W

2010-01-01

Through a cooperative effort between the US Department of Energy and the Russian Federation (RF) Ministry of Defense (MOD) a Personnel Reliability Program (PRP) for the nuclear handlers within the RF MOD is at the stage of implementation. Sustaining the program is of major significance for long term success. This paper will discuss the elements of the RF PRP and the equipment needs for implementation. Program requirements, documentation needs, training, and assurances of appropriate equipment use will be addressed.

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha}more » co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.« less

Effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer.

PubMed

Cai, Yong; Sheng, Zhao-Ying; Chen, Yun; Bai, Chong

2014-01-01

To explore the effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer (NSCLC). NSCNC cell line A549 was selected to explore the effect of Withaferin A on A549 cellular proliferation, apoptosis and the PI3K/Akt signal pathway capable of regulating tumor biological behavior by assessment of cellular proliferation, cellular apoptotic rates and cellular cycling as well as by immuno-blotting. Withaferin A could inhibit A549 cellular proliferation and the control rate was dosage-dependent (P<0.05), which also increased time-dependently with the same dosage of Withaferin A (P<0.05). The apoptotic indexes in A549 cells treated with 0, 2.5, 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A for 48 h were significantly different (P<0.05). In addition, the apoptotic rates of each group in both early and advanced stages were higher than those in 0 μmol·L-1 (P<0.05), which were evidently higher after 48 h than those after 24 h (P<0.05). A549 cells treated by Withaferin A for 48 h were markedly lower in Bcl-2 level and obviously higher in Bax and cleaved caspase-3 levels than those treated by 0 μmol·L-1 Withaferin A (P<0.05), and there were significant differences among 5, 10 and 20 μmol·L-1 Withaferin A (P<0.05). The ratios of A549 cells treated by Withaferin A for 48 h in G0/G1 stage were higher than those in 0 μmol·L-1 , while those in S and G2/M stages were obviously lower than those in G2/M stage, and there were significant differences in 5.0, 10.0 and 20.0 μmol·L-1 Withaferin A (P<0.05). Additionally, p-Akt/Akt values were in reverse association with dosage, and the differences were significant (P<0.05). Withaferin A can inhibit the proliferation and apoptosis of A549 cells by suppressing activation of the PI3K/Akt pathways.

Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

PubMed

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

2016-03-01

The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL). The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. We demonstrated that Kpnβ1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways.

PubMed

Wu, Dong-Dong; Gao, Ying-Ran; Li, Tao; Wang, Da-Yong; Lu, Dan; Liu, Shi-Yu; Hong, Ya; Ning, Hui-Bin; Liu, Jun-Ping; Shang, Jia; Shi, Jun-Feng; Wei, Jian-She; Ji, Xin-Ying

2018-05-02

PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

Aberrant activation of M phase proteins by cell proliferation-evoking carcinogens after 28-day administration in rats.

PubMed

Yafune, Atsunori; Taniai, Eriko; Morita, Reiko; Hayashi, Hitomi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2013-06-07

We have previously reported that hepatocarcinogens increase liver cells expressing p21(Cip1), a G1 checkpoint protein and M phase proteins after 28-day treatment in rats. This study aimed to identify early prediction markers of carcinogens available in many target organs after 28-day treatment in rats. Immunohistochemical analysis was performed on Ki-67, p21(Cip1) and M phase proteins [nuclear Cdc2, phospho-Histone H3 (p-Histone H3), Aurora B and heterochromatin protein 1α (HP1α)] with carcinogens targeting different organs. Carcinogens targeting thyroid (sulfadimethoxine; SDM), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole; BHA), glandular stomach (catechol; CC), and colon (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and chenodeoxycholic acid) were examined using a non-carcinogenic toxicant (caprolactam) and carcinogens targeting other organs as negative controls. All carcinogens increased Ki-67(+), nuclear Cdc2(+), p-Histone H3(+) or Aurora B(+) carcinogenic target cells, except for both colon carcinogens, which did not increase cell proliferation. On the other hand, p21(Cip1+) cells increased with SDM and CC. HP1α responded only to BHA. Results revealed carcinogens evoking cell proliferation concurrently induced cell cycle arrest at M phase or showing chromosomal instability reflecting aberration in cell cycle regulation, irrespective of target organs, after 28-day treatment. Therefore, M phase proteins may be early prediction markers of carcinogens evoking cell proliferation in many target organs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp

DOE PAGES

Altieri, Amanda S.; Ladner, Jane E.; Li, Zhuo; ...

2016-05-03

Here, proliferating cell nuclear antigen (PCNA) forms a trimeric ring that encircles duplex DNA and acts as an anchor for a number of proteins involved in DNA metabolic processes. PCNA has two structurally similar domains (I and II) linked by a long loop (inter-domain connector loop, IDCL) on the outside of each monomer of the trimeric structure that makes up the DNA clamp. All proteins that bind to PCNA do so via a PCNA-interacting peptide (PIP) motif that binds near the IDCL. A small protein, called TIP, binds to PCNA and inhibits PCNA-dependent activities although it does not contain amore » canonical PIP motif. The X-ray crystal structure of TIP bound to PCNA reveals that TIP binds to the canonical PIP interaction site, but also extends beyond it through a helix that relocates the IDCL. TIP alters the relationship between domains I and II within the PCNA monomer such that the trimeric ring structure is broken, while the individual domains largely retain their native structure. Small angle X-ray scattering (SAXS) confirms the disruption of the PCNA trimer upon addition of the TIP protein in solution and together with the X-ray crystal data, provides a structural basis for the mechanism of PCNA inhibition by TIP.« less

The relationship between apoptosis and the expression of proliferating cell nuclear antigen and the clinical stages in gastric carcinoma.

PubMed

Tao, K; Chen, D; Tian, Y; Lu, X; Yang, X

2000-01-01

The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5 +/- 3.7)% and (49.8 +/- 15.9)% respectively, and the rate of AI/PI was 0.13 +/- 0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P < 0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage II to IV (P < 0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

The impact of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature terminology in the routine diagnosis of thyroid tumours.

PubMed

Jaconi, M; Manzoni, M; Pincelli, A I; Giardini, V; Scardilli, M; Smith, A; Fellegara, G; Pagni, F

2017-12-01

Due to the recent proposal of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice. A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically-treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III-IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC-like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1). In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC-like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low-risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations. © 2017 John Wiley & Sons Ltd.

The cell proliferation antigen Ki-67 organises heterochromatin

PubMed Central

Sobecki, Michal; Mrouj, Karim; Camasses, Alain; Parisis, Nikolaos; Nicolas, Emilien; Llères, David; Gerbe, François; Prieto, Susana; Krasinska, Liliana; David, Alexandre; Eguren, Manuel; Birling, Marie-Christine; Urbach, Serge; Hem, Sonia; Déjardin, Jérôme; Malumbres, Marcos; Jay, Philippe; Dulic, Vjekoslav; Lafontaine, Denis LJ; Feil, Robert; Fisher, Daniel

2016-01-01

Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression. DOI: http://dx.doi.org/10.7554/eLife.13722.001 PMID:26949251

[Estimation of cost-saving for reducing radioactive waste from nuclear medicine facilities by implementing decay in storage (DIS) in Japan].

PubMed

Kida, Tetsuo; Hiraki, Hitoshi; Yamaguchi, Ichirou; Fujibuchi, Toshioh; Watanabe, Hiroshi

2012-01-01

DIS has not yet been implemented in Japan as of 2011. Therefore, even if risk was negligible, medical institutions have to entrust radioactive temporal waste disposal to Japan Radio Isotopes Association (JRIA) in the current situation. To decide whether DIS should be implemented in Japan or not, cost-saving effect of DIS was estimated by comparing the cost that nuclear medical facilities pay. By implementing DIS, the total annual cost for all nuclear medical facilities in Japan is estimated to be decreased to 30 million yen or less from 710 million yen. DIS would save 680 million yen (96%) per year.

Worldwide Report, Nuclear Development and Proliferation

DTIC Science & Technology

1984-12-19

Growth 29 Atucha Employees Issue Demands 20 BRAZIL Uranium Enrichment Program To Begin Feb 1985 (0 ESTADO DE SAO PAULO, 6 Nov 84) 31 Nuclear...Program in ’Decisive Period’ (Jose Roberto Arruda; 0 ESTADO DE SAO PAULO, 18 Nov 84) 33 Future Enrichment Plant Construction in Ceara Announced (0...ESTADO DE SAO PAULO, 20 Oct 84) 35 - b PERU Editorial Questions Status of Several IPEN Programs (FOLHA DE SAO PAULO, 14 Oct 84) 36 Briefs

NRF2 Mediates Neuroblastoma Proliferation and Resistance to Retinoic Acid Cytotoxicity in a Model of In Vitro Neuronal Differentiation.

PubMed

de Miranda Ramos, Vitor; Zanotto-Filho, Alfeu; de Bittencourt Pasquali, Matheus Augusto; Klafke, Karina; Gasparotto, Juciano; Dunkley, Peter; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

2016-11-01

Retinoic acid (RA) morphogenetic properties have been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells' proliferation rate and increased cells' sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated nuclear factor erythroid 2-like factor 2 (NRF2) activation by RA. None of these effects were obtained with Trolox ® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of the ERK 1/2 and PI3K/AKT pathways revealed to be equally required to promote NRF2 activation and necessary for RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments; thus, this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols.

Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

PubMed

An, Shucai; Soe, Kyaw; Akamatsu, Maki; Hishikawa, Yoshitaka; Koji, Takehiko

2012-11-01

Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70% partial hepatectomy (PH) in rats fed with rat chow with 3% carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-κB) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-κB, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.

Peroxisome proliferator-activated receptor {alpha}-independent peroxisome proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Xiuguo; Tanaka, Naoki; Nakajima, Takero

2006-08-11

Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR{alpha}-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPAR{alpha} dependence in the assay system. Surprisingly, a novel type of PPAR{alpha}-independent peroxisome proliferation and enlargement was uncovered in PPAR{alpha}-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11{alpha}, might be associated with the PPAR{alpha}-independent peroxisome proliferation at least in part.

Proliferation Control Regimes: Background and Status

DTIC Science & Technology

2006-12-26

developing a national capability to conduct forensic analysis of evidence from bio-crimes and terrorism. Given the difficulty of differentiating between...North Korea in 2004 galvanized the international community to examine strengthening implementation of national export controls and interdiction ... interdiction of WMD-related equipment shipments at sea, on land, and by air. President Bush announced the Proliferation Security Initiative (PSI) on May 31

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis

PubMed Central

Mehdi, Muhammad Zain; Nagi, Abdul Hanan; Naseem, Nadia

2016-01-01

ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis.

PubMed

Mehdi, Muhammad Zain; Nagi, Abdul Hanan; Naseem, Nadia

2016-01-01

Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they

Implementing quantum logic gates with gradient ascent pulse engineering: principles and practicalities.

PubMed

Rowland, Benjamin; Jones, Jonathan A

2012-10-13

We briefly describe the use of gradient ascent pulse engineering (GRAPE) pulses to implement quantum logic gates in nuclear magnetic resonance quantum computers, and discuss a range of simple extensions to the core technique. We then consider a range of difficulties that can arise in practical implementations of GRAPE sequences, reflecting non-idealities in the experimental systems used.

Non-Nuclear Testing of Compact Reactor Technologies at NASA MSFC

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Pearson, J. Boise; Godfroy, Thomas J.

2011-01-01

Safe, reliable, compact, autonomous, long-life fission systems have numerous potential applications, both terrestrially and in space. Technologies and facilities developed in support of these systems could be useful to a variety of concepts. At moderate power levels, fission systems can be designed to operate for decades without the need for refueling. In addition, fast neutron damage to cladding and structural materials can be maintained at an acceptable level. Nuclear design codes have advanced to the stage where high confidence in the behavior and performance of a system can be achieved prior to initial testing. To help ensure reactor affordability, an optimal strategy must be devised for development and qualification. That strategy typically involves a combination of non-nuclear and nuclear testing. Non-nuclear testing is particularly useful for concepts in which nuclear operating characteristics are well understood and nuclear effects such as burnup and radiation damage are not likely to be significant. To be mass efficient, a SFPS must operate at higher coolant temperatures and use different types of power conversion than typical terrestrial reactors. The primary reason is the difficulty in rejecting excess heat to space. Although many options exist, NASA s current reference SFPS uses a fast spectrum, pumped-NaK cooled reactor coupled to a Stirling power conversion subsystem. The reference system uses technology with significant terrestrial heritage while still providing excellent performance. In addition, technologies from the SFPS system could be applicable to compact terrestrial systems. Recent non-nuclear testing at NASA s Early Flight Fission Test Facility (EFF-TF) has helped assess the viability of the reference SFPS and evaluate methods for system integration. In July, 2011 an Annular Linear Induction Pump (ALIP) provided by Idaho National Laboratory was tested at the EFF-TF to assess performance and verify suitability for use in a10 kWe technology

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

Application of a Virtual Reactivity Feedback Control Loop in Non-Nuclear Testing of a Fast Spectrum Reactor

NASA Technical Reports Server (NTRS)

Bragg-Sitton, Shannon M.; Forsbacka, Matthew

2004-01-01

For a compact, fast-spectrum reactor, reactivity feedback is dominated by core deformation at elevated temperature. Given the use of accurate deformation measurement techniques, it is possible to simulate nuclear feedback in non-nuclear electrically heated reactor tests. Implementation of simulated reactivity feedback in response to measured deflection is being tested at the NASA Marshall Space Flight Center Early Flight Fission Test Facility (EFF-TF). During tests of the SAFE-100 reactor prototype, core deflection was monitored using a high resolution camera. "virtual" reactivity feedback was accomplished by applying the results of Monte Carlo calculations (MCNPX) to core deflection measurements; the computational analysis was used to establish the reactivity worth of van'ous core deformations. The power delivered to the SAFE-100 prototype was then dusted accordingly via kinetics calculations, The work presented in this paper will demonstrate virtual reactivity feedback as core power was increased from 1 kilowatt(sub t), to 10 kilowatts(sub t), held approximately constant at 10 kilowatts (sub t), and then allowed to decrease based on the negative thermal reactivity coefficient.

Human peroxisome proliferator-activated receptor mRNA and protein expression during development

EPA Science Inventory

The peroxisome proliferator-activated receptors (PPAR) are nuclear hormone receptors that regulate lipid and glucose homeostasis and are important in reproduction and development. PPARs are targets ofpharmaceuticals and are also activated by environmental contaminants, including ...

An analysis of international nuclear fuel supply options

NASA Astrophysics Data System (ADS)

Taylor, J'tia Patrice

. The material movement module is the largest of the three, and the two other modules that assess nonproliferation and economics of the options are dependent on its output. Proliferation resistance measures from literature are modified and incorporated in MEPAT. The module to assess the nonproliferation of the supply options allows the user to specify defining attributes for the fuel cycle processes, and determines significant quantities of materials as well as measures of proliferation resistance. The measure is dependent on user-input and material information. The economics module allows the user to specify costs associated with different processes and other aspects of the fuel cycle. The simulation tool then calculates economic measures that relate the cost of the fuel cycle to electricity production. The second part of this dissertation consists of an examination of four scenarios of fuel supply option using MEPAT. The first is a simple scenario illustrating the modules and basic functions of MEPAT. The second scenario recreates a fuel supply study reported earlier in literature, and compares MEPAT results with those reported earlier for validation. The third, and a rather realistic, scenario includes four nuclear programs with one program entering the nuclear energy market. The fourth scenario assesses the reactor options available to the Hashemite Kingdom of Jordan, which is currently assessing available options to introduce nuclear power in the country. The methodology developed and implemented in MEPAT to analyze the material, proliferation and economics of nuclear fuel supply options is expected to help simplify and assess different reactor and fuel options available to utilities, government agencies and international organizations.

The Nuclear Posture Review (NPR) : are we safer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brune, Nancy E.

2010-07-01

Nuclear Posture Review (NPR) is designed to make world safer by reducing the role of U.S. nuclear weapons and reducing the salience of nuclear weapons. U.S. also seeks to maintain a credible nuclear deterrent and reinforce regional security architectures with missile defenses and other conventional military capabilities. But recent studies suggest that nuclear proliferation is a direct response to the perceived threat of U.S. conventional capabilities not U.S. nuclear stockpile. If this is true, then the intent of the NPR to reduce the role and numbers of nuclear weapons and strengthen conventional military capabilities may actually make the world lessmore » safe. First stated objective of NPR is to reduce the role and numbers of U.S. nuclear weapons, reduce the salience of nuclear weapons and move step by step toward eliminating them. Second stated objective is a reaffirmation of U.S. commitment to maintaining a strong deterrent which forms the basis of U.S. assurances to allies and partners. The pathway - made explicit throughout the NPR - for reducing the role and numbers of nuclear weapons while maintaining a credible nuclear deterrent and reinforcing regional security architectures is to give conventional forces and capabilities and missile defenses (e.g. non-nuclear elements) a greater share of the deterrence burden.« less

miR-543 is up-regulated in gefitinib-resistant non-small cell lung cancer and promotes cell proliferation and invasion via phosphatase and tensin homolog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Mingjun; Chen, Wei; Yu, Hongmei

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-543 is up-regulated in gefitinib-resistant non-small cell lung cancer (NSCLC) patients comparing gefitinib-sensitive ones. It promotes NSCLC cell proliferation by negatively regulates its target gene PTEN. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-543 mimics. Transwell assay showed that miR-543 mimics promotes the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-543 directly binds to the 3'untranslated region of PTEN, and western blotting showed thatmore » miR-543 suppresses the expression of PTEN at the protein level. This study indicates that miR-543 promotes proliferation and invasion of NSCLC cell lines by PTEN. The miR-543 may represent a potential therapeutic target for gefitinib-resistant NSCLC intervention. - Highlights: • miR-543 is highly expressed in gefitinib-resistant NSCLC. • miR-543 promotes the proliferation and invasion of NSCLC cells. • miR-543 inhibitors inhibits the proliferation and invasion of NSCLC cells. • miR-543 targets 3′ UTR of PTEN in NSCLC cells. • miR-543 inhibits PTEN in NSCLC cells.« less

Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells

PubMed Central

Hanson, Lindsey; Zhao, Wenting; Lou, Hsin-Ya; Lin, Ziliang Carter; Lee, Seok Woo; Chowdary, Praveen; Cui, Yi; Cui, Bianxiao

2016-01-01

The mechanical stability and deformability of the cell nucleus are crucial to many biological processes, including migration, proliferation and polarization. In vivo, the cell nucleus is frequently subjected to deformation on a variety of length and time scales, but current techniques for studying nuclear mechanics do not provide access to subnuclear deformation in live functioning cells. Here we introduce arrays of vertical nanopillars as a new method for the in situ study of nuclear deformability and the mechanical coupling between the cell membrane and the nucleus in live cells. Our measurements show that nanopillar-induced nuclear deformation is determined by nuclear stiffness, as well as opposing effects from actin and intermediate filaments. Furthermore, the depth, width and curvature of nuclear deformation can be controlled by varying the geometry of the nanopillar array. Overall, vertical nanopillar arrays constitute a novel approach for non-invasive, subcellular perturbation of nuclear mechanics and mechanotransduction in live cells. PMID:25984833

Dose-related cell proliferation in medaka (Oryzias latipes) after N-nitrosodiethylamine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortego, L.S.; Hawkins, W.E.; Walker, W.W.

1994-12-31

Cell proliferation is important in toxic and carcinogenic mechanisms. Carcinogens such as N-nitrosodiethylamine (DEN) that cause necrotizing injury stimulate cell proliferation as part of an injury-repair mechanism. A stimulus to cell division in an organ with a low rate of cell division, such as the liver, may initiate or enhance the carcinogenicity of a chemical. The authors examined the effect of DEN exposure on cell proliferation in the liver of medaka (Oryzias latipes). Two age groups (6 and 56 days post-hatch) were exposed to DEN continuously at 5 doses (0.0, 2.5, 5.0, 10.0, and 20.0 ppm) for 28 days. Cellmore » proliferation was measured using the proliferating cell nuclear antigen (PCNA) assay two months post-initiation of DEN exposure. The assay involves monoclonal antibody detection of PCNA, an auxiliary protein of DNA polymerase delta which is, expressed during cell division. Results suggested that cell proliferation paralleled the DEN dose and that age at initiation of exposure did not affect this relationship. The increase in cell proliferation appeared to be a sustained response from that initiated during DEN exposure. The study suggests that cell proliferation in medaka is an important component in carcinogenesis and is related to carcinogen exposure dose.« less

Immunohistochemical study of p53 and proliferating cell nuclear antigen expression in odontogenic keratocyst and periapical cyst.

PubMed

Sajeevan, Thara Purath; Saraswathi, Tillai Rajasekaran; Ranganathan, Kannan; Joshua, Elizabeth; Rao, Uma Devi K

2014-07-01

p53 protein is a product of p53 gene, which is now classified as a tumor suppressor gene. The gene is a frequent target for mutation, being seen as a common step in the pathogenesis of many human cancers. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and plays a critical role in initiation of cell proliferation. The aim of this study is to assess and compare the expression of p53 and PCNA in lining epithelium of odontogenic keratocyst (OKC) and periapical cyst (PA). A total of 20 cases comprising 10 OKC and 10 PA were included in retrospective study. Three paraffin section of 4 μm were cut, one was used for routine hematoxylin and eosin stain, while the other two were used for immunohistochemistry. Statistical analysis was performed using Chi-square test. The level of staining and intensity were assessed in all these cases. OKC showed PCNA expression in all cases (100%), whereas in perapical cyst only 60% of cases exhibited PCNA staining. (1) OKC showed p53 expression in 6 cases (60%) whereas in PA only 10% of the cases exhibited p53 staining. Chi-square test showed PCNA staining intensity was more significant than p53 in OKC. (2) The staining intensity of PA using p53, PCNA revealed that PCNA stating intensity was more significant than p53. OKC shows significant proliferative activity than PA using PCNA and p53. PCNA staining was more intense when compared with p53 in both OKC and PA.

Comparative analysis of cell proliferation ratio in plaque and erosive oral lichen planus: An immunohistochemical study.

PubMed

Redder, C Pramod; Pandit, Siddharth; Desai, Dinkar; Kandagal, V Suresh; Ingaleshwar, Pramod S; Shetty, Sharan J; Vibhute, Nupura

2014-05-01

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S-phase of the cell cycle. Detection of this protein represents a useful marker of the proliferation status of lesions. This study has been carried out to evaluate the cell proliferation rate in oral lichen planus (OLP) and comparison between plaque and erosive lichen planus, which indicates the potential for malignant transformation. This study was comprised of 64 cases of histologically proven lichen planus, out of which 32 cases of plaque and erosive each was taken. Two sections were taken from each, one for H and E staining to verify histological diagnosis according to Eisenberg criteria, other sections were stained according to super sensitive polymer horse radish peroxidise method for identifying immunohistochemical expression of PCNA. Data were statistically analyzed by Tukey high-range statistical domain test. Statistically significant P value was considered <0.05. In two types of lichen planus, erosive type (66.86%) showed higher expression of PCNA followed by plaque (17.07%). Overall, P value was <0.001, which was statistically significant. It indicates that proliferation activity is more in erosive lichen planus followed by plaque type, which ultimately results in increased rate of malignant transformation. PCNA is a good nuclear protein marker to evaluate the proliferation status of OLP. Out of the two types of lichen planus, erosive type possesses more proliferative ratio and chances of malignant change is more in this type. It emphasizes the importance of long-term follow-up with erosive type when compared with plaque type.

78 FR 67289 - Continuation of the National Emergency With Respect to the Proliferation of Weapons of Mass...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... economy of the United States posed by the proliferation of nuclear, biological, and chemical weapons (weapons of mass destruction) and the means of delivering such weapons. On July 28, 1998, the President... November 7, 2013 Continuation of the National Emergency With Respect to the Proliferation of Weapons of...

Experience and advantages in implementation of educational program in network form at Department «Closed nuclear fuel cycle Technologies» of National Research Nuclear University «MEPhI»

NASA Astrophysics Data System (ADS)

Beygel‧, A. G.; Kutsenko, K. V.; Lavrukhin, A. A.; Magomedbekov, E. P.; Pershukov, V. A.; Sofronov, V. L.; Tyupina, E. A.; Zhiganov, A. N.

2017-01-01

The experience of implementation of the basic educational program of magistracy on direction «Nuclear Physics and Technologies» in a network form is presented. Examples of joint implementation of the educational process with employers organizations, other universities and intranet mobility of students are given.

U.S.-Russian cooperation in nuclear disarmament and nonproliferation

NASA Astrophysics Data System (ADS)

Podvig, Pavel

2010-02-01

The United States and Russia, the two largest nuclear powers, have a special obligation to provide leadership in nuclear disarmament and in strengthening the nuclear non-proliferation regime. In the past year the two countries made an effort to restart the arms control process by concluding a new treaty that would bring their legal disarmament obligations in line with the realities of their post-cold war relationships. The process of negotiating deeper nuclear reductions in the new environment turned out to be rather difficult, since the approaches that the countries used in the past are not well suited to dealing with issues like conversion of strategic nuclear delivery systems to conventional missions, tactical nuclear weapons, or dismantlement of nuclear warheads. This presentation considers the recent progress in U.S.-Russian arms control process and outlines the key issues at the negotiations. It also considers prospects for further progress in bilateral nuclear disarmament and issues that will be encountered at later stages of the process. The author argues that success of the arms reductions will depend on whether the United States and Russia will be able to build an institutional framework for cooperation on a range of issues - from traditional arms control to securing nuclear materials and from missile defense to strengthening the international nuclear safeguards. )

Nuclear programs in India and Pakistan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mian, Zia

India and Pakistan launched their respective nuclear programs in the 1940s and 1950s with considerable foreign technical support, especially from the United States Atoms for Peace Program. The technology and training that was acquired served as the platform for later nuclear weapon development efforts that included nuclear weapon testing in 1974 and in 1998 by India, and also in 1998 by Pakistan - which had illicitly acquired uranium enrichment technology especially from Europe and received assistance from China. As of 2013, both India and Pakistan were continuing to produce fissile material for weapons, in the case of India also formore » nuclear naval fuel, and were developing a diverse array of ballistic and cruise missiles. International efforts to restrain the South Asian nuclear build-up have been largely set aside over the past decade as Pakistani support became central for the U.S. war in Afghanistan and as U.S. geopolitical and economic interests in supporting the rise of India, in part as a counter to China, led to India being exempted both from U.S non-proliferation laws and international nuclear trade guidelines. In the absence of determined international action and with Pakistan blocking the start of talks on a fissile material cutoff treaty, nuclear weapon programs in South Asia are likely to keep growing for the foreseeable future.« less

Nuclear programs in India and Pakistan

NASA Astrophysics Data System (ADS)

Mian, Zia

2014-05-01

India and Pakistan launched their respective nuclear programs in the 1940s and 1950s with considerable foreign technical support, especially from the United States Atoms for Peace Program. The technology and training that was acquired served as the platform for later nuclear weapon development efforts that included nuclear weapon testing in 1974 and in 1998 by India, and also in 1998 by Pakistan - which had illicitly acquired uranium enrichment technology especially from Europe and received assistance from China. As of 2013, both India and Pakistan were continuing to produce fissile material for weapons, in the case of India also for nuclear naval fuel, and were developing a diverse array of ballistic and cruise missiles. International efforts to restrain the South Asian nuclear build-up have been largely set aside over the past decade as Pakistani support became central for the U.S. war in Afghanistan and as U.S. geopolitical and economic interests in supporting the rise of India, in part as a counter to China, led to India being exempted both from U.S non-proliferation laws and international nuclear trade guidelines. In the absence of determined international action and with Pakistan blocking the start of talks on a fissile material cutoff treaty, nuclear weapon programs in South Asia are likely to keep growing for the foreseeable future.

A non-invasive implementation of a mixed domain decomposition method for frictional contact problems

NASA Astrophysics Data System (ADS)

Oumaziz, Paul; Gosselet, Pierre; Boucard, Pierre-Alain; Guinard, Stéphane

2017-11-01

A non-invasive implementation of the Latin domain decomposition method for frictional contact problems is described. The formulation implies to deal with mixed (Robin) conditions on the faces of the subdomains, which is not a classical feature of commercial software. Therefore we propose a new implementation of the linear stage of the Latin method with a non-local search direction built as the stiffness of a layer of elements on the interfaces. This choice enables us to implement the method within the open source software Code_Aster, and to derive 2D and 3D examples with similar performance as the standard Latin method.

OCT despeckling via weighted nuclear norm constrained non-local low-rank representation

NASA Astrophysics Data System (ADS)

Tang, Chang; Zheng, Xiao; Cao, Lijuan

2017-10-01

As a non-invasive imaging modality, optical coherence tomography (OCT) plays an important role in medical sciences. However, OCT images are always corrupted by speckle noise, which can mask image features and pose significant challenges for medical analysis. In this work, we propose an OCT despeckling method by using non-local, low-rank representation with weighted nuclear norm constraint. Unlike previous non-local low-rank representation based OCT despeckling methods, we first generate a guidance image to improve the non-local group patches selection quality, then a low-rank optimization model with a weighted nuclear norm constraint is formulated to process the selected group patches. The corrupted probability of each pixel is also integrated into the model as a weight to regularize the representation error term. Note that each single patch might belong to several groups, hence different estimates of each patch are aggregated to obtain its final despeckled result. Both qualitative and quantitative experimental results on real OCT images show the superior performance of the proposed method compared with other state-of-the-art speckle removal techniques.

Non-malignant thyroid disease after exposure to radioactive elements during nuclear explosion: a neglected issue.

PubMed

Wiwanitkit, Viroj

2012-01-01

Recent nuclear explosion in Japan led to a great concern regarding its detrimental effects on health. As obtained data imply the increased risk of thyroid cancer, the prevention is widely suggested. Also the adverse effect of leaked radioactive elements can lead to non-malignant thyroid disease, which is neglected. In this article, non-malignant thyroid disease after exposure to radioactive elements during nuclear explosion was reviewed and discussed.

76 FR 80305 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... the Atomic Energy Act of 1954, as amended, and the Nuclear Non- Proliferation Act of 1978, as amended... the Nuclear Non-Proliferation Act of 1978, as amended. Dated: December 16, 2011. Ellen O. Tauscher...

The Nuclear Nonproliferation Treaty in Context

NASA Astrophysics Data System (ADS)

Davenport, Kelsey

2017-01-01

The 1968 Nuclear Nonproliferation Treaty (NPT) is the cornerstone of multilateral efforts to prevent the spread of nuclear weapons and promote efforts toward complete disarmament. In the grand bargain of the NPT, states foreswore pursuit of nuclear weapons in exchange for access to nuclear technology and limited nuclear arsenals to the five states (China, France, Russia, the United Kingdom and the United States) that tested such weapons before the NPT's conception. Now in its seventh decade, the NPT regime is embraced by the vast majority of the world's nations and is viewed as a critical element of international security. However, despite past successes in halting efforts in several states to pursue nuclear weapons, near universal adherence, and only one withdrawal (North Korea), the NPT regime is at a critical crossroads. The treaty has proven unable to adapt to new challenges, such as emerging technologies that threaten operational strategic realities, the devolution of state authority to non-state actors and institutions, and growing dissatisfaction with slow pace of nuclear disarmament. Additionally, the treaty leaves open critical questions, including whether or not state parties have the `right' to pursue technologies that allow for domestic production of fuels for nuclear reactors and if modernization programs for nuclear warheads are inconsistent with the treaty. If these questions remain unresolved, the international community will find itself ill prepared to confront emerging proliferation challenges and the NPT, the linchpin of international nonproliferation and disarmament efforts, may begin to erode.

Mode of action framework analysis for receptor-mediated toxicity: the Peroxisome Proliferator-Activated Receptor alpha (PPARα) as a case study

EPA Science Inventory

Therapeutic hypolipidemic agents and industrial chemicals that cause peroxisome proliferation and induce liver tumors in rodents activate the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα). Research has elucidated the cellular and molecular events by w...

Non-plane-wave Hartree-Fock states and nuclear homework potentials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutierrez, G.; Plastino, A.; de Llano, M.

1979-12-01

It is shown that non-plane-wave single-particle Hartree-Fock orbitals giving rise to a ''spin-density-wave-like'' structure give lower energy than plane waves beyond a certain relatively low density in both nuclear and neutron matter with homework pair potentials v/sub 1/ and v/sub 2/.

Rethinking the Unthinkable: Selective Proliferation and US Nuclear Strategy

DTIC Science & Technology

2011-06-01

Equally commendable are the efforts of the SAASS librarian Sandhya "Sandy" Malladi and the SAASS secretaries Sheila McKitt and Kelly Rhodes. These...Nuclear Deterrence and Global Security in Transition, 177. 20 Barry R . Schneider, Future War and Counterproliferation: US Military Responses to Nbc...develop states prepared to conduct themselves as nuclear weapons 42 Barre R . Seguin, "Why Did Poland Choose the F-16?," The Marshall Center

Overview of DOE-NE Proliferation and Terrorism Risk Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadasivan, Pratap

2012-08-24

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

Proteasome dynamics between proliferation and quiescence stages of Saccharomyces cerevisiae.

PubMed

Yedidi, Ravikiran S; Fatehi, Amatullah K; Enenkel, Cordula

The ubiquitin-proteasome system (UPS) plays a critical role in cellular protein homeostasis and is required for the turnover of short-lived and unwanted proteins, which are targeted by poly-ubiquitination for degradation. Proteasome is the key protease of UPS and consists of multiple subunits, which are organized into a catalytic core particle (CP) and a regulatory particle (RP). In Saccharomyces cerevisiae, proteasome holo-enzymes are engaged in degrading poly-ubiquitinated substrates and are mostly localized in the nucleus during cell proliferation. While in quiescence, the RP and CP are sequestered into motile and reversible storage granules in the cytoplasm, called proteasome storage granules (PSGs). The reversible nature of PSGs allows the proteasomes to be transported back into the nucleus upon exit from quiescence. Nuclear import of RP and CP through nuclear pores occurs via the canonical pathway that includes the importin-αβ heterodimer and takes advantage of the Ran-GTP gradient across the nuclear membrane. Dependent on the growth stage, either inactive precursor complexes or mature holo-enzymes are imported into the nucleus. The present review discusses the dynamics of proteasomes including their assembly, nucleo-cytoplasmic transport during proliferation and the sequestration of proteasomes into PSGs during quiescence. [Formula: see text].

Implementation of generalized quantum measurements for unambiguous discrimination of multiple non-orthogonal coherent states.

PubMed

Becerra, F E; Fan, J; Migdall, A

2013-01-01

Generalized quantum measurements implemented to allow for measurement outcomes termed inconclusive can perform perfect discrimination of non-orthogonal states, a task which is impossible using only measurements with definitive outcomes. Here we demonstrate such generalized quantum measurements for unambiguous discrimination of four non-orthogonal coherent states and obtain their quantum mechanical description, the positive-operator valued measure. For practical realizations of this positive-operator valued measure, where noise and realistic imperfections prevent perfect unambiguous discrimination, we show that our experimental implementation outperforms any ideal standard-quantum-limited measurement performing the same non-ideal unambiguous state discrimination task for coherent states with low mean photon numbers.

Non-Formal Education Implementations in Turkey: Issues and Latest Challenges

ERIC Educational Resources Information Center

Bilir, Mehmet

2007-01-01

The aim of this article is to analyse the latest implementations and issues raised in Turkish non-formal education from a historical perspective in Turkey. The high population rate and lack of adequate educational opportunities for adults and migration from rural areas to urban areas caused many educational, social and cultural problems in…

Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.

PubMed

Piqueras, Laura; Reynolds, Andrew R; Hodivala-Dilke, Kairbaan M; Alfranca, Arántzazu; Redondo, Juan M; Hatae, Toshihisa; Tanabe, Tadashi; Warner, Timothy D; Bishop-Bailey, David

2007-01-01

The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-beta/delta in endothelial cells remains unclear. Interestingly, the selective PPARbeta/delta ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPARbeta/delta in endothelial cell proliferation and angiogenesis. Western blot analysis indicated PPARbeta/delta was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPARbeta/delta target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPARbeta/delta. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation. PPARbeta/delta is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders.

SkyNet: A Modular Nuclear Reaction Network Library

NASA Astrophysics Data System (ADS)

Lippuner, Jonas; Roberts, Luke F.

2017-12-01

Almost all of the elements heavier than hydrogen that are present in our solar system were produced by nuclear burning processes either in the early universe or at some point in the life cycle of stars. In all of these environments, there are dozens to thousands of nuclear species that interact with each other to produce successively heavier elements. In this paper, we present SkyNet, a new general-purpose nuclear reaction network that evolves the abundances of nuclear species under the influence of nuclear reactions. SkyNet can be used to compute the nucleosynthesis evolution in all astrophysical scenarios where nucleosynthesis occurs. SkyNet is free and open source, and aims to be easy to use and flexible. Any list of isotopes can be evolved, and SkyNet supports different types of nuclear reactions. SkyNet is modular so that new or existing physics, like nuclear reactions or equations of state, can easily be added or modified. Here, we present in detail the physics implemented in SkyNet with a focus on a self-consistent transition to and from nuclear statistical equilibrium to non-equilibrium nuclear burning, our implementation of electron screening, and coupling of the network to an equation of state. We also present comprehensive code tests and comparisons with existing nuclear reaction networks. We find that SkyNet agrees with published results and other codes to an accuracy of a few percent. Discrepancies, where they exist, can be traced to differences in the physics implementations.

Overexpression of PHRF1 attenuates the proliferation and tumorigenicity of non-small cell lung cancer cells.

PubMed

Wang, Yadong; Wang, Haiyu; Pan, Teng; Li, Li; Li, Jiangmin; Yang, Haiyan

2016-09-27

The aim of this study was to investigate the potential role of PHRF1 in lung tumorigenesis. Western blot analysis was used to detect the expression of proteins. Quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, soft agar assay and tumor formation assay in nude mice were applied. Cell cycle distribution was analyzed by flow cytometry. The lower level of PHRF1 mRNA was observed in human lung cancer tissues than that in paracancerous tissues. The decreased expression of PHRF1 protein was observed in H1299 and H1650 cell lines than that in 16HBE and BEAS-2B cell lines. The decreased expression of PHRF1 protein was observed in malignant 16HBE cells compared to control cells. The reduced expression of PHRF1 protein was observed in mice lung tissues treated with BaP than that in control group. Overexpression of PHRF1 inhibited H1299 cell proliferation, colony formation in vitro and growth of tumor xenograft in vivo, and arrested cell cycle in G1 phase. The decreased expression of TGIF and c-Myc proteins and the increased expression of p21 protein were observed in H1299-PHRF1 cells compared with H1299-pvoid cells. In conclusion, our findings suggest that overexpression of PHRF1 attenuated the proliferation and tumorigenicity of non-small cell lung cancer cell line of H1299.

5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis

PubMed Central

2012-01-01

Background Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has a high mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT) allowed to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and survival of NSCLC. Methods siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used. Results The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung cancer cell lines with 4-azasteroids did not significantly inhibit proliferation. Conclusions In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained proliferation of NSCLC cell lines. PMID:22257483

5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis.

PubMed

Kapp, Friedrich G; Sommer, Anette; Kiefer, Thomas; Dölken, Gottfried; Haendler, Bernard

2012-01-18

Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has a high mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT) allowed to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and survival of NSCLC. siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used. The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung cancer cell lines with 4-azasteroids did not significantly inhibit proliferation. In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained proliferation of NSCLC cell lines.

Long non-coding RNA Gm2199 rescues liver injury and promotes hepatocyte proliferation through the upregulation of ERK1/2.

PubMed

Gao, Qiang; Gu, Yunyan; Jiang, Yanan; Fan, Li; Wei, Zixiang; Jin, Haobin; Yang, Xirui; Wang, Lijuan; Li, Xuguang; Tai, Sheng; Yang, Baofeng; Liu, Yan

2018-05-22

Long non-coding RNAs (lncRNAs) are a new class of regulators of various human diseases. This study was designed to explore the potential role of lncRNAs in experimental hepatic damage. In vivo hepatic damage in mice and in vitro hepatocyte damage in AML12 and NCTC1469 cells were induced by carbon tetrachloride (CCl 4 ) treatments. Expression profiles of lncRNAs and mRNAs were analyzed by microarray. Bioinformatics analyses were conducted to predict the potential functions of differentially expressed lncRNAs with respect to hepatic damage. Overexpression of lncRNA Gm2199 was achieved by transfection of the pEGFP-N1-Gm2199 plasmid in vitro and adeno-associated virus-Gm2199 in vivo. Cell proliferation and viability was detected by cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assay. Protein and mRNA expressions of extracellular signal-regulated kinase-1/2 (ERK1/2) were detected by western blot and quantitative real-time reverse-transcription PCR (qRT-PCR). Microarray analysis identified 190 and 148 significantly differentially expressed lncRNAs and mRNAs, respectively. The analyses of lncRNA-mRNA co-expression and lncRNA-biological process networks unraveled potential roles of the differentially expressed lncRNAs including Gm2199 in the pathophysiological processes leading to hepatic damage. Gm2199 was downregulated in both damaged livers and hepatocyte lines. Overexpression of Gm2199 restored the reduced proliferation of damaged hepatocyte lines and increased the expression of ERK1/2. Overexpression of Gm2199 also promoted the proliferation and viability of normal hepatocyte lines and increased the level of p-ERK1/2. Overexpression of Gm2199 in vivo also protected mouse liver injury induced by CCl 4 , evidenced by more proliferating hepatocytes, less serum alanine aminotransferase, less serum aspartate aminotransferase, and decreased hepatic hydroxyproline. The ability of Gm2199 to maintain hepatic proliferation capacity indicates it as a novel anti-liver damage

Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells.

PubMed

Müller, Maike; Raabe, Oksana; Addicks, Klaus; Wenisch, Sabine; Arnhold, Stefan

2011-03-01

In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

Promoting Intercultural Competency in the Nuclear Workplace

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachner K. M.

Intercultural preparedness training is a staple of many workplaces that require international competence, including government, business, and non-profits. Even highly experienced diplomats are often advised to attend training sessions on this topic. Intercultural preparedness training promises to be especially relevant and useful for professionals working in the field of nuclear nonproliferation, including in the application of international nuclear safeguards. This paper outlines the fundamental philosophies underlying a training program that will benefit professionals in the nuclear arena, whether practitioners of nonproliferation or other sub-fields relying on international cooperation and collaboration, and how such a training program might be implemented efficiently.

lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1.

PubMed

Yu, L; Fang, F; Lu, S; Li, X; Yang, Y; Wang, Z

2017-05-01

Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a potential target for NSCLC treatment.

The United Arab Emirates Nuclear Program and Proposed U.S. Nuclear Cooperation

DTIC Science & Technology

2009-12-23

reactors deployed” in the UAE. Some Members of Congress had welcomed the UAE government’s stated commitments not to pursue proliferation-sensitive...for the planned nuclear reactor or on handling spent reactor fuel. (...continued) May...firms and the UAE related to the UAE’s proposed nuclear program has already taken place. In August 2008, Virginia’s Thorium Power Ltd. signed two

Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells.

PubMed

Hodroj, Dana; Serhal, Kamar; Maiorano, Domenico

2017-09-03

The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation. In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore. Here we review recent findings related to an additional Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated during collision between transcription and replication, and upon DNA damage. Activation of a DNA damage response pathway dependent upon the ATR kinase, a major regulator of replication fork progression, stimulates translocation of the Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA double strand breaks only in proliferating cells. Overall these observations put forward Ddx19 as an important novel mediator of the crosstalk between transcription and replication.

Intelligence briefing on smuggling of nuclear material and the role of international crime organizations, and on the proliferation of cruise and ballistic missiles. Hearing before the Committee on Armed Services, United States Senate, One Hundred Fourth Congress, First Session, January 31, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The hearing addresses nuclear smuggling and the role of international crime organizations in the proliferation of cruise and ballistic missiles. The demise of the Soviet Union has weakened the control in Russia over nuclear materials. Statements of government officials are included along with documents submitted for the record.

PUBLIC HEARING TRANSCRIPT: FEDERAL NON-NUCLEAR ENERGY RESEARCH AND DEVELOPMENT PROGRAM

EPA Science Inventory

This document presents the proceedings of three days of public hearings on the Federal Non-nuclear Energy Research and Development Program. The document is presented in three sections: (1) Future Energy Patterns and Levels of Coal Use, (2) Solar Energy and Conservation, and (3) O...

The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells.

PubMed

Luo, Xia; Yin, Ping; Coon V, John S; Cheng, You-Hong; Wiehle, Ronald D; Bulun, Serdar E

2010-05-15

To evaluate the effects of selective P receptor (PR) modulator CDB4124 on cell proliferation and apoptosis in cultured human uterine leiomyoma smooth muscle (LSM) cells and control myometrial smooth muscle (MSM) cells in matched uteri. Laboratory research. Academic medical center. Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related symptoms. Treatment of primary LSM and MSM cells with CDB4124 (10(-8)-10(-6) M) or vehicle for 24, 48, or 72 hours. Western blot for protein expression of proliferating cell nuclear antigen, cleaved polyadenosine 5'-diphosphate-ribose polymerase, Bcl-2, and Krüppel-like transcription factor 11; 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate viable cell numbers; and real-time polymerase chain reaction (PCR) to quantify messenger RNA (mRNA) levels. Treatment with CDB4124 significantly decreased levels of the proliferation marker proliferating cell nuclear antigen, the number of viable LSM cells, and the antiapoptotic protein Bcl-2. On the other hand, treatment with CDB4124 increased levels of the apoptosis marker cleaved polyadenosine 5'-diphosphate-ribose polymerase and the tumor suppressor Krüppel-like transcription factor 11 in a dose- and time-dependent manner in LSM cells. In matched MSM cells, however, CDB4124 did not affect cell proliferation or apoptosis. CDB4124 selectively inhibits proliferation and induces apoptosis in LSM but not in MSM cells. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cell Proliferation and Epidermal Growth Factor Signaling in Non-small Cell Lung Adenocarcinoma Cell Lines Are Dependent on Rin1

PubMed Central

Tomshine, Jin C.; Severson, Sandra R.; Wigle, Dennis A.; Sun, Zhifu; Beleford, Daniah A. T.; Shridhar, Vijayalakshmi; Horazdovsky, Bruce F.

2009-01-01

Rin1 is a Rab5 guanine nucleotide exchange factor that plays an important role in Ras-activated endocytosis and growth factor receptor trafficking in fibroblasts. In this study, we show that Rin1 is expressed at high levels in a large number of non-small cell lung adenocarcinoma cell lines, including Hop62, H650, HCC4006, HCC827, EKVX, HCC2935, and A549. Rin1 depletion from A549 cells resulted in a decrease in cell proliferation that was correlated to a decrease in epidermal growth factor receptor (EGFR) signaling. Expression of wild type Rin1 but not the Rab5 guanine nucleotide exchange factor-deficient Rin1 (Rin1Δ) complemented the Rin1 depletion effects, and overexpression of Rin1Δ had a dominant negative effect on cell proliferation. Rin1 depletion stabilized the cell surface levels of EGFR, suggesting that internalization was necessary for robust signaling in A549 cells. In support of this conclusion, introduction of either dominant negative Rab5 or dominant negative dynamin decreased A549 proliferation and EGFR signaling. These data demonstrate that proper internalization and endocytic trafficking are critical for EGFR-mediated signaling in A549 cells and suggest that up-regulation of Rin1 in A549 cell lines may contribute to their proliferative nature. PMID:19570984

An implementation of the look-ahead Lanczos algorithm for non-Hermitian matrices, part 1

NASA Technical Reports Server (NTRS)

Freund, Roland W.; Gutknecht, Martin H.; Nachtigal, Noel M.

1990-01-01

The nonsymmetric Lanczos method can be used to compute eigenvalues of large sparse non-Hermitian matrices or to solve large sparse non-Hermitian linear systems. However, the original Lanczos algorithm is susceptible to possible breakdowns and potential instabilities. We present an implementation of a look-ahead version of the Lanczos algorithm which overcomes these problems by skipping over those steps in which a breakdown or near-breakdown would occur in the standard process. The proposed algorithm can handle look-ahead steps of any length and is not restricted to steps of length 2, as earlier implementations are. Also, our implementation has the feature that it requires roughly the same number of inner products as the standard Lanczos process without look-ahead.

Edwin I. Hatch nuclear plant implementation of improved technical specifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahler, S.R.; Pendry, D.

1994-12-31

Edwin I. Hatch nuclear plant consists of two General Electric boiling water reactor/4 units, with a common control room and a common refueling floor. In March 1993, Hatch began conversion of both units` technical specifications utilizing NUREG 1433. The technical specifications amendment request was submitted February 25, 1994. Issuance is scheduled for October 21, 1994, with implementation on March 15, 1994. The current unit-1 technical specifications are in the {open_quotes}custom{close_quotes} format, and the unit-2 technical specifications are in the old standard format. Hatch previously relocated the fire protection and radiological technical specifications requirements. The Hatch conversion will provide consistency betweenmore » the two units, to the extent practicable.« less

Atypical nuclear localization of VIP receptors in glioma cell lines and patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbarin, Alice; Séité, Paule; Godet, Julie

Highlights: • The VIP receptor VPAC1 contains a putative NLS signal. • VPAC1 is predominantly nuclear in GBM cell lines but not VPAC2. • Non-nuclear VPAC1/2 protein expression is correlated with glioma grade. • Nuclear VPAC1 is observed in 50% of stage IV glioma (GBM). - Abstract: An increasing number of G protein-coupled receptors, like receptors for vasoactive intestinal peptide (VIP), are found in cell nucleus. As VIP receptors are involved in the regulation of glioma cell proliferation and migration, we investigated the expression and the nuclear localization of the VIP receptors VPAC1 and VPAC2 in this cancer. First, bymore » applying Western blot and immunofluorescence detection in three human glioblastoma (GBM) cell lines, we observed a strong nuclear staining for the VPAC1 receptor and a weak nuclear VPAC2 receptor staining. Second, immunohistochemical staining of VPAC1 and VPAC2 on tissue microarrays (TMA) showed that the two receptors were expressed in normal brain and glioma tissues. Expression in the non-nuclear compartment of the two receptors significantly increased with the grade of the tumors. Analysis of nuclear staining revealed a significant increase of VPAC1 staining with glioma grade, with up to 50% of GBM displaying strong VPAC1 nuclear staining, whereas nuclear VPAC2 staining remained marginal. The increase in VPAC receptor expression with glioma grades and the enhanced nuclear localization of the VPAC1 receptors in GBM might be of importance for glioma progression.« less

Branches of the NF-κB signaling pathway regulate proliferation of oval cells in rat liver regeneration.

PubMed

Zhao, W M; Qin, Y L; Niu, Z P; Chang, C F; Yang, J; Li, M H; Zhou, Y; Xu, C S

2016-03-24

The NF-kB (nuclear factor kB) pathway is involved in the proliferation of many cell types. To explore the mechanism of the NF-kB signaling pathway underlying the oval cell proliferation during rat liver regeneration, the Rat Genome 230 2.0 Array was used to detect expression changes of NF-kB signaling pathway-related genes in oval cells. The results revealed that the expression levels of many genes in the NF-kB pathway were significantly changed. This included 48 known genes and 16 homologous genes, as well as 370 genes and 85 homologous genes related to cell proliferation. To further understand the biological significance of these changes, an expression profile function was used to analyze the potential biological processes. The results showed that the NF-kB pathway promoted oval cell proliferation mainly through three signaling branches; the tumor necrosis factor alpha branch (TNF-a pathway), the growth factor branch, and the chemokine branch. An integrated statistics method was used to define the key genes in the NF-kB pathway. Seven genes were identified to play vital roles in the NF-kB pathway. To confirm these results, the protein content, including two key genes (TNF and FGF11) and two non-key genes (CCL2 and TNFRSF12A), were analyzed using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The results were generally consistent with those of the array data. To conclude, three branches and seven key genes were involved in the NF-kB signaling pathway that regulates oval cell proliferation during rat liver regeneration.

Safeguards Guidance Document for Designers of Commercial Nuclear Facilities: International Nuclear Safeguards Requirements and Practices For Uranium Enrichment Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robert Bean; Casey Durst

2009-10-01

This report is the second in a series of guidelines on international safeguards requirements and practices, prepared expressly for the designers of nuclear facilities. The first document in this series is the description of generic international nuclear safeguards requirements pertaining to all types of facilities. These requirements should be understood and considered at the earliest stages of facility design as part of a new process called “Safeguards-by-Design.” This will help eliminate the costly retrofit of facilities that has occurred in the past to accommodate nuclear safeguards verification activities. The following summarizes the requirements for international nuclear safeguards implementation at enrichmentmore » plants, prepared under the Safeguards by Design project, and funded by the U.S. Department of Energy (DOE) National Nuclear Security Administration (NNSA), Office of NA-243. The purpose of this is to provide designers of nuclear facilities around the world with a simplified set of design requirements and the most common practices for meeting them. The foundation for these requirements is the international safeguards agreement between the country and the International Atomic Energy Agency (IAEA), pursuant to the Treaty on the Non-proliferation of Nuclear Weapons (NPT). Relevant safeguards requirements are also cited from the Safeguards Criteria for inspecting enrichment plants, found in the IAEA Safeguards Manual, Part SMC-8. IAEA definitions and terms are based on the IAEA Safeguards Glossary, published in 2002. The most current specification for safeguards measurement accuracy is found in the IAEA document STR-327, “International Target Values 2000 for Measurement Uncertainties in Safeguarding Nuclear Materials,” published in 2001. For this guide to be easier for the designer to use, the requirements have been restated in plainer language per expert interpretation using the source documents noted. The safeguards agreement is

New Non-Intrusive Inspection Technologies for Nuclear Security and Nonproliferation

NASA Astrophysics Data System (ADS)

Ledoux, Robert J.

2015-10-01

Comprehensive monitoring of the supply chain for nuclear materials has historically been hampered by non-intrusive inspection systems that have such large false alarm rates that they are impractical in the flow of commerce. Passport Systems, Inc. (Passport) has developed an active interrogation system which detects fissionable material, high Z material, and other contraband in land, sea and air cargo. Passport's design utilizes several detection modalities including high resolution imaging, passive radiation detection, effective-Z (EZ-3D™) anomaly detection, Prompt Neutrons from Photofission (PNPF), and Nuclear Resonance Fluorescence (NRF) isotopic identification. These technologies combine to: detect fissionable, high-Z, radioactive and contraband materials, differentiate fissionable materials from high-Z shielding materials, and isotopically identify actinides, Special Nuclear Materials (SNM), and other contraband (e.g. explosives, drugs, nerve agents). Passport's system generates a 3-D image of the scanned object which contains information such as effective-Z and density, as well as a 2-D image and isotopic and fissionable information for regions of interest.

Non-nuclear Testing of Reactor Systems in the Early Flight Fission Test Facilities (EFF-TF)

NASA Technical Reports Server (NTRS)

VanDyke, Melissa; Martin, James

2004-01-01

The Early Flight Fission-Test Facility (EFF-TF) can assist in the &sign and development of systems through highly effective non-nuclear testing of nuclear systems when technical issues associated with near-term space fission systems are "non-nuclear" in nature (e.g. system s nuclear operations are understood). For many systems. thermal simulators can he used to closely mimic fission heat deposition. Axial power profile, radial power profile. and fuel pin thermal conductivity can be matched. In addition to component and subsystem testing, operational and lifetime issues associated with the steady state and transient performance of the integrated reactor module can be investigated. Instrumentation at the EFF-TF allows accurate measurement of temperature, pressure, strain, and bulk core deformation (useful for accurately simulating nuclear behavior). Ongoing research at the EFF-TF is geared towards facilitating research, development, system integration, and system utilization via cooperative efforts with DOE laboratories, industry, universities, and other NASA centers. This paper describes the current efforts for the latter portion of 2003 and beginning of 2004.

Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric oxide on cell proliferation and programmed cell death.

PubMed

Trulsson, Lena M; Gasslander, Thomas; Svanvik, Joar

2004-10-01

The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-kappaB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of N(omega)-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-kappaB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [(3)H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor kappaB (NF-kappaB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-kappaB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-kappaB activation seems not to inhibit apoptosis nor promote cell proliferation.

Spectral implementation of some quantum algorithms by one- and two-dimensional nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Das, Ranabir; Kumar, Anil

2004-10-01

Quantum information processing has been effectively demonstrated on a small number of qubits by nuclear magnetic resonance. An important subroutine in any computing is the readout of the output. "Spectral implementation" originally suggested by Z. L. Madi, R. Bruschweiler, and R. R. Ernst [J. Chem. Phys. 109, 10603 (1999)], provides an elegant method of readout with the use of an extra "observer" qubit. At the end of computation, detection of the observer qubit provides the output via the multiplet structure of its spectrum. In spectral implementation by two-dimensional experiment the observer qubit retains the memory of input state during computation, thereby providing correlated information on input and output, in the same spectrum. Spectral implementation of Grover's search algorithm, approximate quantum counting, a modified version of Berstein-Vazirani problem, and Hogg's algorithm are demonstrated here in three- and four-qubit systems.

Involvement of glutathione/glutathione S-transferase antioxidant system in butyrate-inhibited vascular smooth muscle cell proliferation.

PubMed

Ranganna, Kasturi; Mathew, Omana P; Yatsu, Frank M; Yousefipour, Zivar; Hayes, Barbara E; Milton, Shirlette G

2007-11-01

Vascular smooth muscle cell (VSMC) proliferation is an important etiological factor in vascular proliferative diseases such as primary atherosclerosis, hypertension, arterial and in-stent restenosis, and transplant vasculopathy. Our studies established that butyrate, a bacterial fermentation product of dietary fiber and a chromatin modulator, is a potent inhibitor of VSMC proliferation. The cardiovascular health benefits of a high-fiber diet, the principle source of butyrate in the body, have been known for a long time, however, very little is known about the antiatherogenic potential of butyrate. Because oxidative stress plays an important role in the pathogenesis of atherosclerosis, we examined involvement of the glutathione/glutathione S-transferase (GST) antioxidant system in butyrate's inhibition of VSMC proliferation. Treatment of proliferating VSMCs with butyrate leads to the induction of several GSTs. Interestingly, our study also demonstrated the nuclear localization of GST-P1 (GST-7-7), which is considered to be a cytosolic protein; this was demonstrated using immunostaining and was corroborated by western blotting. Also, the butyrate-induced antiproliferative action, and the induction of GST-P1 and its nuclear localization are downregulated when butyrate is withdrawn. Furthermore, assessment of intracellular glutathione levels reveals their augmentation by butyrate. Conversely, butyrate treatment reduces the levels of reactive oxygen species in VSMCs. Collectively, the butyrate-treatment-related increase in glutathione content, the reduction in reactive oxygen species, the upregulation of GST and the nuclear localization of GST-P1 in growth-arrested VSMCs imply that butyrate's antiproliferative action involves modulation of the cellular redox state. Thus, induction of the glutathione/GST antioxidant system appears to have other regulatory role(s) besides detoxification and regulation of the cellular redox state, for example, cell-cycle control and cell

Cell proliferation of Paramecium tetraurelia under simulated microgravity

NASA Astrophysics Data System (ADS)

Sawai, S.; Mogami, Y.; Baba, S. A.

Paramecium is known to proliferate faster under microgravity in space and slower under hypergravity Experiments using axenic culture medium have demonstrated that the hypergravity affected directly on the proliferation of Paramecium itself Kato et al 2003 In order to assess the mechanisms underlying the physiological effects of gravity on cell proliferation Paramecium tetraurelia was grown under simulated microgravity performed by clinorotation and the time course of the proliferation was investigated in detail on the basis of the logistic analysis P tetraurelia was cultivated in a closed chamber in which cells were confined without air babbles reducing the shear stresses and turbulence under the rotation The chamber is made of quartz and silicone rubber film the former is for the optically-flat walls for the measurement of cell density by means of a non-invasive laser optical-slice method and the latter for gas exchange Because the closed chamber has an inner dimension of 3 times 3 times 60 mm Paramecium does not accumulate at the top of the chamber despite its negative gravitactic behavior We measured the cell density at regular time intervals without breaking the configuration of the chamber and analyzed the proliferation parameters by fitting the data to a logistic equation Clinorotation had the effects of reducing the proliferation of P tetraurelia It reduced both the saturation cell density and the maximum proliferation rate although it had little effect on the

IMPROVED TECHNNOLOGY TO PREVENT ILLICIT TRAFFICKING IN NUCLEAR MATERIALS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, J H

2005-07-20

The proliferation of nuclear, chemical, and biological weapons (collectively known as weapons of mass destruction, or WMD) and the potential acquisition and use of WMD against the world by terrorists are extremely serious threats to international security. These threats are complex and interrelated. There are myriad routes to weapons of mass destruction--many different starting materials, material sources, and production processes. There are many possible proliferators--threshold countries, rogue states, state-sponsored or transnational terrorists groups, domestic terrorists, and even international crime organizations. Motives for acquiring and using WMD are similarly wide ranging--from a desire to change the regional power balance, deny accessmore » to a strategic area, or alter international policy to extortion, revenge, or hate. Because of the complexity of this threat landscape, no single program, technology, or capability--no silver bullet--can solve the WMD proliferation and terrorism problem. An integrated program is needed that addresses the WMD proliferation and terrorism problem from end to end, from prevention to detection, reversal, and response, while avoiding surprise at all stages, with different activities directed specifically at different types of WMD and proliferators. Radiation detection technologies are an important tool in the prevention of proliferation. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. The radiation properties of nuclear materials, particularly highly enriched uranium (HEU), make the detection of smuggled nuclear materials technically difficult. A number of efforts are under way to devise improved detector materials and instruments and to identify novel signatures that could be detected. Key applications of this work include monitoring for radioactive

Temporal high-pass non-uniformity correction algorithm based on grayscale mapping and hardware implementation

NASA Astrophysics Data System (ADS)

Jin, Minglei; Jin, Weiqi; Li, Yiyang; Li, Shuo

2015-08-01

In this paper, we propose a novel scene-based non-uniformity correction algorithm for infrared image processing-temporal high-pass non-uniformity correction algorithm based on grayscale mapping (THP and GM). The main sources of non-uniformity are: (1) detector fabrication inaccuracies; (2) non-linearity and variations in the read-out electronics and (3) optical path effects. The non-uniformity will be reduced by non-uniformity correction (NUC) algorithms. The NUC algorithms are often divided into calibration-based non-uniformity correction (CBNUC) algorithms and scene-based non-uniformity correction (SBNUC) algorithms. As non-uniformity drifts temporally, CBNUC algorithms must be repeated by inserting a uniform radiation source which SBNUC algorithms do not need into the view, so the SBNUC algorithm becomes an essential part of infrared imaging system. The SBNUC algorithms' poor robustness often leads two defects: artifacts and over-correction, meanwhile due to complicated calculation process and large storage consumption, hardware implementation of the SBNUC algorithms is difficult, especially in Field Programmable Gate Array (FPGA) platform. The THP and GM algorithm proposed in this paper can eliminate the non-uniformity without causing defects. The hardware implementation of the algorithm only based on FPGA has two advantages: (1) low resources consumption, and (2) small hardware delay: less than 20 lines, it can be transplanted to a variety of infrared detectors equipped with FPGA image processing module, it can reduce the stripe non-uniformity and the ripple non-uniformity.

ACCIDENTS AND UNSCHEDULED EVENTS ASSOCIATED WITH NON-NUCLEAR ENERGY RESOURCES AND TECHNOLOGY

EPA Science Inventory

Accidents and unscheduled events associated with non-nuclear energy resources and technology are identified for each step in the energy cycle. Both natural and anthropogenic causes of accidents or unscheduled events are considered. Data concerning these accidents are summarized. ...

The arms race and nuclear war

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barash, D.P.

Addressing the history, physics, biology, economics, politics, psychology, and ethics of nuclear armaments, the author provides a survey of diverse facets of the nuclear controversy. The study encompasses such key areas as nuclear hardware and technology; the short- and long-term effects of nuclear weapons; strategic doctrine, deterrence and defense policy; the arms race, arms control, and nuclear proliferation; and the economic impact, psychology, and ethics of nuclear armaments. A ''Policy Issues'' section, presenting both the advocate and opponent sides of the debate, is included with each chapter.

Non-local classical optical correlation and implementing analogy of quantum teleportation

PubMed Central

Sun, Yifan; Song, Xinbing; Qin, Hongwei; Zhang, Xiong; Yang, Zhenwei; Zhang, Xiangdong

2015-01-01

This study reports an experimental realization of non-local classical optical correlation from the Bell's measurement used in tests of quantum non-locality. Based on such a classical Einstein–Podolsky–Rosen optical correlation, a classical analogy has been implemented to the true meaning of quantum teleportation. In the experimental teleportation protocol, the initial teleported information can be unknown to anyone and the information transfer can happen over arbitrary distances. The obtained results give novel insight into quantum physics and may open a new field of applications in quantum information. PMID:25779977

On The Export Control Of High Speed Imaging For Nuclear Weapons Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, Scott Avery; Altherr, Michael Robert

Since the Manhattan Project, the use of high-speed photography, and its cousins flash radiography1 and schieleren photography have been a technological proliferation concern. Indeed, like the supercomputer, the development of high-speed photography as we now know it essentially grew out of the nuclear weapons program at Los Alamos2,3,4. Naturally, during the course of the last 75 years the technology associated with computers and cameras has been export controlled by the United States and others to prevent both proliferation among non-P5-nations and technological parity among potential adversaries among P5 nations. Here we revisit these issues as they relate to high-speed photographicmore » technologies and make recommendations about how future restrictions, if any, should be guided.« less

Nucleoplasmic calcium regulates cell proliferation through legumain.

PubMed

Andrade, Viviane; Guerra, Mateus; Jardim, Camila; Melo, Flavia; Silva, Wamberto; Ortega, Jose M; Robert, Marie; Nathanson, Michael H; Leite, Fatima

2011-09-01

Nucleoplasmic Ca(2+) regulates cell growth in the liver, but the proteins through which this occurs are unknown. We used Rapid Subtraction Hybridization (RaSH) to subtract genes in SKHep1 liver cells expressing the Ca(2+) buffer protein parvalbumin (PV) targeted to the nucleus, from genes in cells expressing a mutated form of nuclear-targeted PV which has one of two Ca(2+)-binding sites inactivated. The subtraction permitted the selection of genes whose expression was affected by a small alteration in nuclear Ca(2+) concentration. The asparaginyl endopeptidase legumain (LGMN) was identified in this screening. When Ca(2+) was buffered in the nucleus of SKHep1 cells, LGMN mRNA was decreased by 97%, in part by a transcriptional mechanism, and decreased expression at the protein level was observed by immunoblot and immunofluorescence. Treatment with hepatocyte growth factor increased LGMN expression. Knockdown of LGMN by siRNA decreased proliferation of SKHep1 cells by ∼50% as measured both by BrdU uptake and mitotic index, although an inhibitor of LGMN activity did not affect BrdU incorporation. A significant reduction in the fraction of cells in G2/M phase was seen as well. This was associated with increases in the expression of cyclins A and E. Furthermore, LGMN expression was increased in hepatocellular carcinoma cells relative to normal hepatocytes in the same specimens. These findings suggest a new role for LGMN and provide evidence that nuclear Ca(2+) signals regulate cell proliferation in part through the modulation of LGMN expression. Increased expression of LGMN may be involved in liver carcinogenesis. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Nitric oxide regulates stretch-induced proliferation in C2C12 myoblasts.

PubMed

Soltow, Quinlyn A; Lira, Vitor A; Betters, Jenna L; Long, Jodi H D; Sellman, Jeff E; Zeanah, Elizabeth H; Criswell, David S

2010-09-01

Mechanical stretch of skeletal muscle activates nitric oxide (NO) production and is an important stimulator of satellite cell proliferation. Further, cyclooxygenase (COX) activity has been shown to promote satellite cell proliferation in response to stretch. Since COX-2 expression in skeletal muscle can be regulated by NO we sought to determine if NO is required for stretch-induced myoblast proliferation and whether supplemental NO can counter the effects of COX-2 and NF-kappaB inhibitors. C2C12 myoblasts were cultured for 24 h, then switched to medium containing either the NOS inhibitor, L-NAME (200 microM), the COX-2 specific inhibitor NS-398 (100 microM), the NF-kappaB inhibiting antioxidant, PDTC (5 mM), the nitric oxide donor, DETA-NONOate (10-100 microM) or no supplement (control) for 24 h. Subgroups of each treatment were exposed to 1 h of 15% cyclic stretch (1 Hz), and were then allowed to proliferate for 24 h before fixing. Proliferation was measured by BrdU incorporation during the last hour before fixing, and DAPI stain. Stretch induced a twofold increase in nuclear number compared to control, and this effect was completely inhibited by L-NAME, NS-398 or PDTC (P < 0.05). Although DETA-NONOate (10 microM) did not affect basal proliferation, the NO-donor augmented the stretch-induced increase in proliferation and rescued stretch-induced proliferation in NS-398-treated cells, but not in PDTC-treated cells. In conclusion, NO, COX-2, and NF-kappaB are necessary for stretch-induced proliferation of myoblasts. Although COX-2 and NF-kappaB are both involved in basal proliferation, NO does not affect basal growth. Thus, NO requires the synergistic effect of stretch in order to induce muscle cell proliferation.

BET bromodomain proteins are required for glioblastoma cell proliferation.

PubMed

Pastori, Chiara; Daniel, Mark; Penas, Clara; Volmar, Claude-Henry; Johnstone, Andrea L; Brothers, Shaun P; Graham, Regina M; Allen, Bryce; Sarkaria, Jann N; Komotar, Ricardo J; Wahlestedt, Claes; Ayad, Nagi G

2014-04-01

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM). We performed NanoString analysis of GBM tumor samples and controls to identify novel therapeutic targets. Several cell proliferation assays of GBM cell lines and stem cells were used to analyze the efficacy of the drug I-BET151 relative to temozolomide (TMZ) or cell cycle inhibitors. Lastly, we performed xenograft experiments to determine the efficacy of I-BET151 in vivo. We demonstrate that BRD2 and BRD4 RNA are significantly overexpressed in GBM, suggesting that BET protein inhibition may be an effective means of reducing GBM cell proliferation. Disruption of BRD4 expression in glioblastoma cells reduced cell cycle progression. Similarly, treatment with the BET protein inhibitor I-BET151 reduced GBM cell proliferation in vitro and in vivo. I-BET151 treatment enriched cells at the G1/S cell cycle transition. Importantly, I-BET151 is as potent at inhibiting GBM cell proliferation as TMZ, the current chemotherapy treatment administered to GBM patients. Since I-BET151 inhibits GBM cell proliferation by arresting cell cycle progression, we propose that BET protein inhibition may be a viable therapeutic option for GBM patients suffering from TMZ resistant tumors.

BET bromodomain proteins are required for glioblastoma cell proliferation

PubMed Central

Pastori, Chiara; Daniel, Mark; Penas, Clara; Volmar, Claude-Henry; Johnstone, Andrea L; Brothers, Shaun P; Graham, Regina M; Allen, Bryce; Sarkaria, Jann N; Komotar, Ricardo J; Wahlestedt, Claes; Ayad, Nagi G

2014-01-01

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM). We performed NanoString analysis of GBM tumor samples and controls to identify novel therapeutic targets. Several cell proliferation assays of GBM cell lines and stem cells were used to analyze the efficacy of the drug I-BET151 relative to temozolomide (TMZ) or cell cycle inhibitors. Lastly, we performed xenograft experiments to determine the efficacy of I-BET151 in vivo. We demonstrate that BRD2 and BRD4 RNA are significantly overexpressed in GBM, suggesting that BET protein inhibition may be an effective means of reducing GBM cell proliferation. Disruption of BRD4 expression in glioblastoma cells reduced cell cycle progression. Similarly, treatment with the BET protein inhibitor I-BET151 reduced GBM cell proliferation in vitro and in vivo. I-BET151 treatment enriched cells at the G1/S cell cycle transition. Importantly, I-BET151 is as potent at inhibiting GBM cell proliferation as TMZ, the current chemotherapy treatment administered to GBM patients. Since I-BET151 inhibits GBM cell proliferation by arresting cell cycle progression, we propose that BET protein inhibition may be a viable therapeutic option for GBM patients suffering from TMZ resistant tumors. PMID:24496381

Validating the disruption of proliferating cell nuclear antigen interactions in the development of targeted cancer therapeutics.

PubMed

Smith, Shanna J; Hickey, Robert J; Malkas, Linda H

2016-01-01

Human DNA replication and repair is a highly coordinated process involving the specifically timed actions of numerous proteins and enzymes. Many of these proteins require interaction with proliferating cell nuclear antigen (PCNA) for activation within the process. The interdomain connector loop (IDCL) of PCNA provides a docking site for many of those proteins, suggesting that this region is critically important in the regulation of cellular function. Previous work in this laboratory has demonstrated that a peptide mimicking a specific region of the IDCL (caPeptide) has the ability to disrupt key protein-protein interactions between PCNA and its binding partners, thereby inhibiting DNA replication within the cells. In this study, we confirm the ability of the caPeptide to disrupt DNA replication function using both intact cell and in vitro DNA replication assays. Further, we were able to demonstrate that treatment with caPeptide results in a decrease of polymerase δ activity that correlates with the observed decrease in DNA replication. We have also successfully developed a surface plasmon resonance (SPR) assay to validate the disruption of the PCNA-pol δ interaction with caPeptide.

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

PubMed Central

Albi, Elisabetta; Perrella, Giuseppina; Lazzarini, Andrea; Cataldi, Samuela; Lazzarini, Remo; Floridi, Alessandro; Ambesi-Impiombato, Francesco Saverio; Curcio, Francesco

2014-01-01

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein. PMID:24979136

Nuclear translocation of glutathione S-transferase {pi} is mediated by a non-classical localization signal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawakatsu, Miho; Goto, Shinji, E-mail: sgoto@nagasaki-u.ac.jp; Yoshida, Takako

2011-08-12

Highlights: {yields} Nuclear translocation of GST{pi} is abrogated by the deletion of the last 16 amino acid residues in the carboxy-terminal region, indicating that residues 195-208 of GST{pi} are required for nuclear translocation. {yields} The lack of a contiguous stretch of positively charged amino acid residues within the carboxy-terminal region of GST{pi}, suggests that the nuclear translocation of GST{pi} is mediated by a non-classical nuclear localization signal. {yields} An in vitro transport assay shows that the nuclear translocation of GST{pi} is dependent on cytosolic factors and ATP. -- Abstract: Glutathione S-transferase {pi} (GST{pi}), a member of the GST family ofmore » multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST{pi} is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST{pi} appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST{pi} was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST{pi}195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST{pi} depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST{pi}, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.« less

Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p.

PubMed

Yang, Bin; Gao, Ge; Wang, Zhixin; Sun, Daju; Wei, Xin; Ma, Yanan; Ding, Youpeng

2018-06-08

Long non-coding RNAs (lncRNAs) are a class of ncRNAs with > 200 nucleotides in length that regulate gene expression. The HOXA transcript at the distal tip (HOTTIP) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOTTIP in prostate cancer (PCa) remain unknown. The aim of the present study was to evaluate the expression and function of HOTTIP in PCa. In the present study, we analyzed HOTTIP expression levels of 86 PCa patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown or overexpression of HOTTIP was performed to explore its roles in cell proliferation, migration, invasion, and cell cycle. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOTTIP and miR-216a-5p in PCa cells. Our results found that HOTTIP was up-regulated in human primary PCa tissues with lymph node metastasis. Knockdown of HOTTIP inhibited PCa cell proliferation, migration and invasion. Overexpression of HOTTIP promoted cell proliferation, migration and invasion of PCa cells. Bioinformatics online programs predicted that HOTTIP sponge miR-216a-5p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOTTIP could negatively regulate the expression of miR-216a-5p in PCa cells. Above all, knockdown of HOTTIP could represent a rational therapeutic strategy for PCa. ©2018 The Author(s).

Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals

PubMed Central

Vogeler, Susanne; Galloway, Tamara S.; Isupov, Michail

2017-01-01

Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor’s functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor’s ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT). Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l), all-trans retinoic acid (ATRA) (0.06 mg/L) and perfluorooctanoic acid (20 mg/L) showed high effects on development (>74% abnormal developed D-shelled larvae), while rosiglitazone (40 mg/L) showed no effect. The results are discussed in relation to a putative direct (TBT) disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests either a

78 FR 9929 - Current Traumatic Brain Injury State Implementation Partnership Grantees; Non-Competitive One...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... Traumatic Brain Injury State Implementation Partnership Grantees; Non-Competitive One-Year Extension Funds...). ACTION: Notice of Non-Competitive One-Year Extension Funds for Current Traumatic Brain Injury (TBI) State... initially authorized by the Traumatic Brain Injury Act of 1996 (Pub. L. 104-166) and was most recently...

Non-equilibrium radiation nuclear reactor

NASA Technical Reports Server (NTRS)

Thom, K.; Schneider, R. T. (Inventor)

1978-01-01

An externally moderated thermal nuclear reactor is disclosed which is designed to provide output power in the form of electromagnetic radiation. The reactor is a gaseous fueled nuclear cavity reactor device which can operate over wide ranges of temperature and pressure, and which includes the capability of processing and recycling waste products such as long-lived transuranium actinides. The primary output of the device may be in the form of coherent radiation, so that the reactor may be utilized as a self-critical nuclear pumped laser.

Implementing Stakeholders' Access to Expertise: Experimenting on Nuclear Installations' Safety Cases - 12160

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilli, Ludivine; Charron, Sylvie

2012-07-01

In 2009 and 2010, the Institute for Nuclear Safety and Radiation Protection (IRSN) led two pilot actions dealing with nuclear installations' safety cases. One concerned the periodical review of the French 900 MWe nuclear reactors, the other concerned the decommissioning of a workshop located on the site of Areva's La Hague fuel-reprocessing plant site in Northwestern France. The purpose of both these programs was to test ways for IRSN and a small number of stakeholders (Non-Governmental Organizations (NGOs) members, local elected officials, etc.) to engage in technical discussions. The discussions were intended to enable the stakeholders to review future applicationsmore » and provide valuable input. The test cases confirmed there is a definite challenge in successfully opening a meaningful dialogue to discuss technical issues, in particular the fact that most expertise reports were not public and the conflict that exists between the contrary demands of transparency and confidentiality of information. The test case also confirmed there are ways to further improvement of stakeholders' involvement. (authors)« less

Export Control Guide: Loose Parts Monitoring Systems for Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langenberg, Donald W.

2012-12-01

This report describes a typical LPMS, emphasizing its application to the RCS of a modern NPP. The report also examines the versatility of AE monitoring technology by describing several nuclear applications other than loose parts monitoring, as well as some non-nuclear applications. In addition, LPMS implementation requirements are outlined, and LPMS suppliers are identified. Finally, U.S. export controls applicable to LPMSs are discussed.

DICOM image quantification secondary capture (DICOM IQSC) integrated with numeric results, regions, and curves: implementation and applications in nuclear medicine

NASA Astrophysics Data System (ADS)

Cao, Xinhua; Xu, Xiaoyin; Voss, Stephan

2017-03-01

In this paper, we describe an enhanced DICOM Secondary Capture (SC) that integrates Image Quantification (IQ) results, Regions of Interest (ROIs), and Time Activity Curves (TACs) with screen shots by embedding extra medical imaging information into a standard DICOM header. A software toolkit of DICOM IQSC has been developed to implement the SC-centered information integration of quantitative analysis for routine practice of nuclear medicine. Primary experiments show that the DICOM IQSC method is simple and easy to implement seamlessly integrating post-processing workstations with PACS for archiving and retrieving IQ information. Additional DICOM IQSC applications in routine nuclear medicine and clinic research are also discussed.

Nuclear threat in the post cold-war era. Monograph