Stability of string defects in models of non-Abelian symmetry breaking

In this paper we describe a new type of topological defect, called a homilia string, which is stabilized via interactions with the string network. Using analytical and numerical techniques, we investigate the stability and dynamics of homilia strings, and show that they can form stable electroweak strings. In SU(2)xU(1) models of symmetry breaking the intersection of two homilia strings is identified with a sphaleron. Due to repulsive forces, the homilia strings seperate, resulting in sphaleron annihilation. It is shown that electroweak homilia string loops cannot stabilize as vortons, which circumvents the adverse cosmological problems associated with stable loops. The consequences for GUT scale homilia strings are also discussed.Comment: 15 pages, revtex, with 8 figures. Submitted to PR

Stability of a spherical flame ball in a porous medium

Gaseous flame balls and their stability to symmetric disturbances are studied numerically and asymptotically, for large activation temperature, within a porous medium that serves only to exchange heat with the gas. Heat losses to a distant ambient environment, affecting only the gas, are taken to be radiative in nature and are represented using two alternative models. One of these treats the heat loss as being constant in the burnt gases and linearizes the radiative law in the unburnt gas (as has been studied elsewhere without the presence of a solid). The other does not distinguish between burnt and unburnt gas and is a continuous dimensionless form of Stefan's law, having a linear part that dominates close to ambient temperatures and a fourth power that dominates at higher temperatures.Numerical results are found to require unusually large activation temperatures in order to approach the asymptotic results. The latter involve two branches of solution, a smaller and a larger flame ball, provided heat losses are not too high. The two radiative heat loss models give completely analogous steady asymptotic solutions, to leading order, that are also unaffected by the presence of the solid which therefore only influences their stability. For moderate values of the dimensionless heat-transfer time between the solid and gas all flame balls are unstable for Lewis numbers greater than unity. At Lewis numbers less than unity, part of the branch of larger flame balls becomes stable, solutions with the continuous radiative law being stable over a narrower range of parameters. In both cases, for moderate heat-transfer times, the stable region is increased by the heat capacity of the solid in a way that amounts, simply, to decreasing an effective Lewis number for determining stability, just as if the heat-transfer time was zero

Human factors and ergonomics systems-based tools for understanding and addressing global problems of the twenty-first century

Sustainability is a systems problem with humans as integral elements of the system. However, sustainability problems usually have a broader scope than socio-technical systems and therefore, require additional considerations. This requires a fuller integration of complex systems understanding into the systems analysis toolset currently available to human factors and ergonomics. In this paper, we outline these complex systems requirements necessary to tackle global problems such as sustainability and then assess how three common systems analysis tools (i.e. Accimap, System Theoretic Accident Mapping and Processes, and Cognitive Work Analysis) stand up against these revised criteria. This assessment is then further explored through applying two of these tools (i.e. Accimap and System Theoretic Accident Mapping and Processes) to a transnational food integrity system problem. This case study shows that no single systems analysis method can be used in isolation to help identify key insights for intervention and that new methods may need to be developed or existing methods need to be adapted to understand these dynamic, adaptive systems. The implications for the further development of systems analysis tools are discussed

A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties

INTRODUCTION: Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored. METHODS: A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(−)immunophenotype and tumorigenicity at limiting dilution. RESULTS: While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(−)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth. CONCLUSIONS: These results establish GTCpFE as a prototype for novel ASA-and fumarate-based anti-inflammatory drugs that: (i) are capable of targeting CSCs, and (ii) may be developed as chemopreventive or therapeutic agents in breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1868-7) contains supplementary material, which is available to authorized users