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Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

Description: Article on the targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids and the potential role in prevention and therapy of cancer.
Date: July 28, 2012
Creator: Shanmugam, Muthu K.; Nguyen, An H.; Kumar, Alan Prem; Tan, Benny K-H & Sethi, Gautam
Partner: UNT College of Arts and Sciences

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

Description: The Utility of Social Modeling for Proliferation Assessment project (PL09-UtilSocial) investigates the use of social and cultural information to improve nuclear proliferation assessments, including nonproliferation assessments, Proliferation Resistance (PR) assessments, safeguards assessments, and other related studies. These assessments often use and create technical information about a host State and its posture towards proliferation, the vulnerability of a nuclear energy system (NES) to an undesired event, and the effectiveness of safeguards. This objective of this project is to find and integrate social and technical information by explicitly considering the role of cultural, social, and behavioral factors relevant to proliferation; and to describe and demonstrate if and how social science modeling has utility in proliferation assessment. This report describes a modeling approach and how it might be used to support a location-specific assessment of the PR assessment of a particular NES. The report demonstrates the use of social modeling to enhance an existing assessment process that relies on primarily technical factors. This effort builds on a literature review and preliminary assessment performed as the first stage of the project and compiled in PNNL-18438. [ T his report describes an effort to answer questions about whether it is possible to incorporate social modeling into a PR assessment in such a way that we can determine the effects of social factors on a primarily technical assessment. This report provides: 1. background information about relevant social factors literature; 2. background information about a particular PR assessment approach relevant to this particular demonstration; 3. a discussion of social modeling undertaken to find and characterize social factors that are relevant to the PR assessment of a nuclear facility in a specific location; 4. description of an enhancement concept that integrates social factors into an existing, technically based nuclear facility assessment; 5. a discussion of a way to ...
Date: October 26, 2009
Creator: Coles, Garill A.; Brothers, Alan J.; Gastelum, Zoe N.; Olson, Jarrod & Thompson, Sandra E.
Partner: UNT Libraries Government Documents Department

Strengthening the foundations of proliferation assessment tools.

Description: Robust and reliable quantitative proliferation assessment tools have the potential to contribute significantly to a strengthened nonproliferation regime and to the future deployment of nuclear fuel cycle technologies. Efforts to quantify proliferation resistance have thus far met with limited success due to the inherent subjectivity of the problem and interdependencies between attributes that lead to proliferation resistance. We suggest that these limitations flow substantially from weaknesses in the foundations of existing methodologies--the initial data inputs. In most existing methodologies, little consideration has been given to the utilization of varying types of inputs--particularly the mixing of subjective and objective data--or to identifying, understanding, and untangling relationships and dependencies between inputs. To address these concerns, a model set of inputs is suggested that could potentially be employed in multiple approaches. We present an input classification scheme and the initial results of testing for relationships between these inputs. We will discuss how classifying and testing the relationship between these inputs can help strengthen tools to assess the proliferation risk of nuclear fuel cycle processes, systems, and facilities.
Date: September 1, 2007
Creator: Rexroth, Paul E.; Saltiel, David H.; Rochau, Gary Eugene; Cleary, Virginia D.; Ng, Selena (AREVA NC, Paris, France); Greneche, Dominique (AREVA NC, Paris, France) et al.
Partner: UNT Libraries Government Documents Department

Semantic-Aware Automatic Parallelization of Modern Applications Using High-Level Abstractions

Description: Automatic introduction of OpenMP for sequential applications has attracted significant attention recently because of the proliferation of multicore processors and the simplicity of using OpenMP to express parallelism for shared-memory systems. However, most previous research has only focused on C and Fortran applications operating on primitive data types. Modern applications using high-level abstractions, such as C++ STL containers and complex user-defined class types, are largely ignored due to the lack of research compilers that are readily able to recognize high-level object-oriented abstractions and leverage their associated semantics. In this paper, we use a source-to-source compiler infrastructure, ROSE, to explore compiler techniques to recognize high-level abstractions and to exploit their semantics for automatic parallelization. Several representative parallelization candidate kernels are used to study semantic-aware parallelization strategies for high-level abstractions, combined with extended compiler analyses. Preliminary results have shown that semantics of abstractions can help extend the applicability of automatic parallelization to modern applications and expose more opportunities to take advantage of multicore processors.
Date: December 21, 2009
Creator: Liao, C; Quinlan, D J; Willcock, J J & Panas, T
Partner: UNT Libraries Government Documents Department

Nonproliferation through international lab-to-lab technology cooperation

Description: At the Lawrence Livermore National Laboratory (LLNL) one of the fastest growing programs as a result of the end of the Cold War is the Nonproliferation, Arms Control, and International Security Directorate (NAI). Since the early 1990's NAI types of programs have grown from a small percentage of LLNL's budget to constitute one of its major programs. NAI's work includes developing instruments to detect chemicals and radiation, analyzing complex national defense problems, anticipating threats to the US, and providing personnel to support national and international efforts in crisis management and arms control. These functions support the US government in dealing with weapons-of-mass-destruction challenges� proliferation, terrorism, and nuclear-state instability. To combat the rapidly emerging chem-bio-terrorism threats, NAI is drawing on LLNL�s advanced technologies in bioscience, microfabrication, and computations to help the Department of Energy (DOE )provide major support to the US government. Half of NAI's effort is directed toward preventing proliferation before it starts, which is the mission of the Proliferation Prevention and Arms Control Program (PPAC). Until recently, our emphasis was on arms control. Now, arms control continues to be an important component while international cooperation and fissile material control are our dominant activities for the Department of Energy. Many of the post-Cold-War changes are highly visible, such as the elimination of nuclear testing by the United States, Russia, China and other major powers; agreements and continuing negotiations to dramatically reduce numbers of nuclear weapons; and increasing international focus on nonproliferation and counterterrorism. Other changes are less highly publicized but are no less significant. One such area is the increasing interactions between DOE Laboratory scientists and their counterparts in the nuclear weapons institutes of the former Soviet Union. Although the large majority of these Lab-to- Lab activities are currently with the FSU, that experience is leading to important and productive ...
Date: September 10, 1998
Creator: Dunlop, W H
Partner: UNT Libraries Government Documents Department

Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3

Description: Article on emodin inhibiting growth and inducing apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3.
Date: October 1, 2013
Creator: Subramaniam, Aruljothi; Shanmugam, Muthu K.; Ong, Tina H.; Li, Feng; Perumal, Ekambaram; Chen, Luxi et al.
Partner: UNT College of Arts and Sciences

PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION WORKING GROUP: METHODOLOGY AND APPLICATIONS

Description: We summarize the technical progress and accomplishments on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of Generation IV nuclear energy systems. We intend the results of the evaluations performed with the methodology for three types of users: system designers, program policy makers, and external stakeholders. The PR and PP Working Group developed the methodology through a series of demonstration and case studies. Over the past few years various national and international groups have applied the methodology to nuclear energy system designs as well as to developing approaches to advanced safeguards.
Date: November 14, 2012
Creator: A., Bari R.; Whitlock, J.; Therios, I.U. & Peterson, P.F.
Partner: UNT Libraries Government Documents Department

Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

Description: Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.
Date: January 1, 2010
Creator: Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia et al.
Partner: UNT Libraries Government Documents Department

ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

Description: Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.
Date: August 8, 2001
Creator: Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J & Brugge, Joan S
Partner: UNT Libraries Government Documents Department

The safeguards options study

Description: The Safeguards Options Study was initiated to aid the International Safeguards Division (ISD) of the DOE Office of Arms Control and Nonproliferation in developing its programs in enhanced international safeguards. The goal was to provide a technical basis for the ISD program in this area. The Safeguards Options Study has been a cooperative effort among ten organizations. These are Argonne National Laboratory, Brookhaven National Laboratory, Idaho National Engineering Laboratory, Lawrence Livermore National Laboratory, Los Alamos National Laboratory, Mound Laboratory, Oak Ridge National Laboratory, Pacific Northwest Laboratories, Sandia National Laboratories, and Special Technologies Laboratory. Much of the Motivation for the Safeguards Options Study is the recognition after the Iraq experience that there are deficiencies in the present approach to international safeguards. While under International Atomic Energy Agency (IAEA) safeguards at their declared facilities, Iraq was able to develop a significant weapons program without being noticed. This is because negotiated safeguards only applied at declared sites. Even so, their nuclear weapons program clearly conflicted with Iraq`s obligations under the Nuclear Nonproliferation Treaty (NPT) as a nonnuclear weapon state.
Date: April 1, 1995
Creator: Hakkila, E.A.; Mullen, M.F.; Olinger, C.T.; Stanbro, W.D.; Olsen, A.P.; Roche, C.T. et al.
Partner: UNT Libraries Government Documents Department

CMC Participation in the Regional Centre for Strategic Studies (RCSS) Workshop: Defense, Technology and Cooperative Security in South Asia

Description: As an ongoing part of the collaborative efforts between the Cooperative Monitoring Center (CMC) at Sandia National Laboratories, the United States Arms Control and Disarmament Agency (ACDA), and U.S. Department of Energy (DOE), staff from the CMC served as faculty in conducting a workshop in Shanghai, China. Sponsor of the workshop was the Regional Centre for Strategic Studies (RCSS) based in Colombo, Sri Lanka. The workshop included participants from throughout South Asia and China. The CMC presented four sessions related to the role of monitoring technologies in promoting regional security and building confidence among nations. Participation in these workshops supports U.S. efforts to further regional cooperation and promote arms control, nonproliferation and other cooperative securily measures and supplements efforts funded by DOE and ACDA over the past four years. The RCSS Shanghai meeting permitted a continued CMC involvement in regionally conducted training for anew generation of leaders in government, the military, and academia throughout South Asia and China. Nuclear issues are clearly a dominant South Asian concern since the nuclear tests of May 1998. However, there remains a strong interest in identifying opportunities for increased trade and reduced tensions in other areas. The RCSS and other regional organizations are enthusiastic about continued CMC involvement in future regional courses.
Date: November 1, 1998
Creator: Biringer, K.L. & Olsen, J.
Partner: UNT Libraries Government Documents Department

Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

Description: This Preliminary Assessment draft report will present the results of a literature search and preliminary assessment of the body of research, analysis methods, models and data deemed to be relevant to the Utility of Social Modeling for Proliferation Assessment research. This report will provide: 1) a description of the problem space and the kinds of information pertinent to the problem space, 2) a discussion of key relevant or representative literature, 3) a discussion of models and modeling approaches judged to be potentially useful to the research, and 4) the next steps of this research that will be pursued based on this preliminary assessment. This draft report represents a technical deliverable for the NA-22 Simulations, Algorithms, and Modeling (SAM) program. Specifically this draft report is the Task 1 deliverable for project PL09-UtilSocial-PD06, Utility of Social Modeling for Proliferation Assessment. This project investigates non-traditional use of social and cultural information to improve nuclear proliferation assessment, including nonproliferation assessment, proliferation resistance assessments, safeguards assessments and other related studies. These assessments often use and create technical information about the State’s posture towards proliferation, the vulnerability of a nuclear energy system to an undesired event, and the effectiveness of safeguards. This project will find and fuse social and technical information by explicitly considering the role of cultural, social and behavioral factors relevant to proliferation. The aim of this research is to describe and demonstrate if and how social science modeling has utility in proliferation assessment.
Date: June 1, 2009
Creator: Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J. & Thompson, Sandra E.
Partner: UNT Libraries Government Documents Department

Rethinking the NPT

Description: The Treaty on the Nonproliferation of Nuclear Weapons (NPT), with over 160 parties, is the most widely adhered to arms control treaty in history, but it has been criticized throughout its existence. In 1995, it is confronting a fateful decision on its extension and its application to today`s world. In many ways it it unfortunate that fundamental questions about the treaty and its role in the post-Cold War world are not being addressed. The environment in which the NPT emerged and flourished has changed fundamentally, including the collapse of one of the founding members, the USSR. Iraq, Iran, and North Korea weapon development programs have raised important questions about its effectiveness. Also, the NPT, with its discrimination between nuclear weapon states (NWSs) and nonnuclear weapon states (NNWSs), is now being questioned and alternatives such as a revival of the Baruch Plan are being put forward, moreover, the NPT has not been the chosen international policy path for dealing with chemical and biological weapons. The paper outlines the history of international policy on nuclear weapons and their proliferation from the 1940`s to today. If the NPT does survive in 1995, can it be strengthened? The full range of issues on NPTs extension will be debated endlessly, but vigilance is necessary, the treaty will have to be tended over time or it will wither and die.
Date: February 1, 1995
Creator: Pilat, J. F.
Partner: UNT Libraries Government Documents Department

Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

Description: Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.
Date: June 26, 2008
Creator: Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J. & Radisky, Derek C.
Partner: UNT Libraries Government Documents Department

Graph algorithms in the titan toolkit.

Description: Graph algorithms are a key component in a wide variety of intelligence analysis activities. The Graph-Based Informatics for Non-Proliferation and Counter-Terrorism project addresses the critical need of making these graph algorithms accessible to Sandia analysts in a manner that is both intuitive and effective. Specifically we describe the design and implementation of an open source toolkit for doing graph analysis, informatics, and visualization that provides Sandia with novel analysis capability for non-proliferation and counter-terrorism.
Date: October 1, 2009
Creator: McLendon, William Clarence, III & Wylie, Brian Neil
Partner: UNT Libraries Government Documents Department

Effects of Peripheral Nerve Injury on the Cells of the Dorsal Root Ganglion: a Role for Primary Cilia

Description: Primary cilia are ubiquitous sensory organelles found on most cell types including cells of the dorsal root ganglia (DRG). The DRG are groups of peripheral neurons that relay sensory information from the periphery to the CNS. Other cell types in the DRG include a type of glial cell, the satellite glial cells (SGCs). The SGCs surround the DRG neurons and, with the neurons, form functional sensory units. Currently are no reports describing the numbers of DRG cells that have cilia. We found that 26% of the SGCs had primary cilia. The incidence of cilia on neurons varied with neuron size, a property that roughly correlates with physiological characteristics. We found that 29% of the small, 16% of the medium and 5% of the large neurons had primary cilia. Primary cilia have been shown to have a role in cell proliferation in a variety of cell types. In some of the cells the cilia mediate the proliferative effects of Sonic hedgehog (Shh). In the CNS, Shh signaling through primary cilia affects proliferation during development as well as following injury, but no studies have looked at this function in the PNS. The SGCs and neurons of the DRG undergo complex changes following peripheral nerve injury such as axotomy. One marked change seen after axotomy is SGC proliferation and at later stages, neuronal death. We found that following axotomy there is a significant increase in the percentage of SGCs with primary cilia. We also found a significant increase in the percentage of medium-sized neurons with primary cilia. In other experiments we tested the idea that Shh plays a role in SGC proliferation. When Shh signaling was blocked following axotomy we found decreased proliferation of SGCs. This is the first report of a change in the percentage of cells with cilia following injury in ...
Date: December 2012
Creator: Smith, Sarah K.
Partner: UNT Libraries

Self-organization of engineered epithelial tubules by differential cellular motility

Description: Patterning of developing tissues arises from a number of mechanisms, including cell shape change, cell proliferation, and cell sorting from differential cohesion or tension. Here, we reveal that differences in cell motility can also lead to cell sorting within tissues. Using mosaic engineered mammary epithelial tubules, we found that cells sorted depending on their expression level of the membrane-anchored collagenase matrix metalloproteinase (MMP)-14. These rearrangements were independent of the catalytic activity of MMP14 but absolutely required the hemopexin domain. We describe a signaling cascade downstream of MMP14 through Rho kinase that allows cells to sort within the model tissues. Cell speed and persistence time were enhanced by MMP14 expression, but only the latter motility parameter was required for sorting. These results indicate that differential directional persistence can give rise to patterns within model developing tissues.
Date: February 4, 2009
Creator: Mori, Hidetoshi; Gjorevski, Nikolce; Inman, Jamie L; Bissell, Mina J & Nelson, Celeste M
Partner: UNT Libraries Government Documents Department

Novel Method for Growing Te-Inclusion-Free CZT

Description: The authors propose a new method for growth of detector-grade CdZnTe (CZT) with reduced concentration and sizes of Te inclusions. The method is designed to impede the formation of Te-rich inclusions in crystals due to the use of new CZT growth method and a unique ampoule design.
Date: June 17, 2008
Creator: Bolotnikov, A.
Partner: UNT Libraries Government Documents Department

HEU to LEU conversion and blending facility: Metal blending alternative to produce LEU oxide for disposal

Description: US DOE is examining options for disposing of surplus weapons-usable fissile materials and storage of all weapons-usable fissile materials. The nuclear material is converted to a form more proliferation- resistant than the original form. Blending HEU (highly enriched uranium) with less-enriched uranium to form LEU has been proposed as a disposition option. Five technologies are being assessed for blending HEU. This document provides data to be used in environmental impact analysis for the HEU-LEU disposition option that uses metal blending with an oxide waste product. It is divided into: mission and assumptions, conversion and blending facility descriptions, process descriptions and requirements, resource needs, employment needs, waste and emissions from plant, hazards discussion, and intersite transportation.
Date: September 1, 1995
Partner: UNT Libraries Government Documents Department