Jack B. Campbell

Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation: Managing the Risks from Climate Extremes at the Local Level

Disasters are most acutely experienced at the local level (high agreement, robust evidence). The reality of disasters in terms of loss of life and property occurs in local places and to local people. These localized impacts can then cascade to have national and international consequences. In this chapter, local refers to a range of places, social groupings, experience, management, institutions, conditions, and sets of knowledge that exist at a sub-national scale. [5.1] Developing strategies for disaster risk management in the context of climate change requires a range of approaches, informed by and customized to specific local circumstances (high agreement, robust evidence). These differences and the context (national to global, urban to rural) in which they are situated shape local vulnerability and local impacts. [5.1] The impacts of climate extremes and weather events may threaten human security at the local level (high agreement, medium evidence). Vulnerability at the local level is attributed to social, political, and economic conditions and drivers including localized environmental degradation and climate change. Addressing disaster risk and climate extremes at the local level requires attention to much wider issues relating to sustainable development. [5.1] While structural measures provide some protection from disasters, they may also create a false sense of safety (high agreement, robust evidence). Such measures result in increased property development, heightened population density, and more disaster exposure. Current regulations and design levels for structural measures may be inadequate under conditions of climate change.

Molecular modeling of γ-lactam analogues of β-lactam antibacterial agents: synthesis and biological evaluation of selected penem and carbapenem analoques

Abstract Computational chemistry made possible the prediction of the three-dimensional structures of γ-lactam analogues of penems and carbapenems before the analogues were made. Molecular superpositioning showed that these novel structures with a 7β-acylamino side-chain present the pharmacophoric groups in close spatial similarity to the groups in biologically active cephalosporin and penicillin antibiotics. This suggests that 8-oxo-7-acylamino-1-azabicyclo[3.3.0]-oct-2-ene-2-carboxylates and the 4-thia-analogues can be accommodated in the same active sites of essential bacterial penicillin-binding proteins where cephalosporins and penicillins are recognized. The syntheses of these compounds are reported. The γ-lactams exhibit low, but detectable levels of antibacterial activity and suggest promise that substantial activity can be achieved with other γ-lactams.

Ly316340: A potent HIV-1 protease inhibitor containing a high affinity octahydrothienopyridine hydroxyethylamine isostere

Abstract Replacement of the decahydroisoquinoline group contained in Ro 31-8959 by a cis -octahydrothienopyridine moiety has provided a high affinity hydroxyethylamine isostere for use in HIV-1 protease inhibitors. Further gains in potency have been realized by incorporation of a sulfur atom into the P 1 benzyl group. Modification by a key P 2 ligand provided LY316440, a potent, orally absorbed inhibitor of HIV-1 protease.