Quantitative Analysis of Diepoxybutane Damage within the Chicken β-globin Domain

In industrial polymer and synthetic rubber production facilities, workers are exposed to 1,3-butadiene. This compound is converted in vivo to 1,2,3,4-diepoxybutane (DEB) and has been linked to increased incidences of cancer in these individuals. Carcinogenesis has been attributed to formation of DEB induced DNA interstrand cross-links. Previous studies have demonstrated that DEB cross-links deoxyguanosine residues within 5'-GNC sequences in synthetic DNA, in restriction fragments, and in defined sequence nucleosomes. The current study utilized the polymerase chain reaction (PCR) to examine DEB damage frequencies within nuclear genes, found within "open" regions of chromatin, as compared to regions of unexpressed sequence that reside in tightly packed, "closed" chromatin, to more closely model DEB reactivity in vivo. These initial studies have been performed in chicken liver homogenates. Preliminarily, we have found a dose-dependent DEB lesion-forming response within "open" chromatin. DEB appears to have little-to-no effect upon regions of "closed" chromatin.

Mapping of Diepoxybutane Damage in the Cytochrome b Domain of Mitochondrial DNA and the β-globin Domain of Nuclear Chicken DNA Using Quantitative PCR

Diepoxybutane (DEB), a known industrial carcinogen, reacts with DNA primarily at the N7 position of deoxyguanosine residues and creates interstrand cross-links at the sequence 5'-GNC. Since N7-N7 cross-links cause DNA to fragment upon heating, quantative polymerase chain reaction (QPCR) is being used in this experiment to measure the amount of DEB damage (lesion frequency) with three different targets-mitochondrial (unpackaged), open chromatin region, and closed chromatin region. Initial measurements of DEB damage within these three targets were not consistent because the template DNA was not the limiting reagent in the PCR. Follow-up PCR trials using a limiting amount of DNA are still in progress although initial experimentation looks promising. Sequencing of these three targets to confirm the primer targets has only been successfully performed for the closed chromatin target and does not match the sequence from NIH used to design that primer pair. Further sequencing trials need to be conducted on all three targets to assure that a mitochondrial, open chromatin, and closed chromatin region are actually being amplified in this experimental series.

The Long Game: Hamas, The IRA, and the Politics of Radicalization in Palestine and Northern Ireland

The value of a comparative study of the two conflicts stems from a remarkable similarity in the structural organization of political violence by its most influential practitioners: the IRA and Hamas. At the core, I have merely tried my best to approach a beguiling question in a fresh, dynamic way. The stultifying discourse of conflict that serves as lingua franca for the Israeli‐Palestinian issue has largely reduced strategic debate to how best the conflict can be managed – not ended. Prime Minister Benjamin Netanyahu’s focus on “economic peace” and unwillingness to commit to a two‐state solution – the consensus that has governed peacemaking for decades – belies such thinking. The Clinton Administration’s cadre of Mideast negotiators operated amidst the most rapid institutionalization of Palestinian democracy in history ‐ yet remained obsessed with Israeli‐Arab “confidence‐building” measures, doing little to legitimize the gains of Oslo. So long as Palestinians continue to view the creation of Israel as “al‐Nakba” – the catastrophe – whilst successive Israeli governments refuse to grant their aspirations any legitimacy, there can be no progress. Peace requires empathy, a substantial compromise in the context of internecine conflict. The “long war” both conflicts have become mandates an equally expansive, broad‐based and labor‐intensive approach – a demanding process that can only be called The Long Game.