Project Specific Risk Consideration from a Portfolio Perspective

Abstract While many companies utilize advanced systems for quantifying and normalizing geologic risks, and some have standardized above ground risk characterization, relatively few use this information effectively when assessing risks at a corporate portfolio or aggregate level. Detailed project assessments are often distilled into expected value representations when combined at a corporate level, leaving the company exposed to potential risk concentrations and aggregate performance variability. This paper demonstrates an approach to assessing value and risks at a portfolio level when the underlying components contain opportunity specific and potentially unique risk drivers. Identifying critical risks at the corporate portfolio level and translating this information into efficient data compilation requests and allocation decisions requires a structured and disciplined approach. While the techniques in describing geological and above ground risks at a project level are commonly applied and portfolio aggregations of projects are routinely conducted, the tripping point for many organizations is in effectively leveraging the detailed stochastic information at a portfolio level. Gaining insights at the aggregate level and maintaining the appropriate perspective on these uncertainties can yield significant value to organizations as they mitigate risks and adjust plans to exploit opportunities. Many of the techniques used to quantify ‘portfolio risk’, such as efficient frontier risk measures, multi-objective scoring, or combined approaches fail in terms of providing decision makers with tangible and practical guidance as to the real impact of specific decisions on objectives. This paper codifies an approach that makes it possible to align the degree of acceptable corporate level uncertainties (risk) with the underlying, project level descriptions. This basic methodology may be employed and expanded to a wide range of asset types and diverse portfolio sets, independent of company size or complexity. A portfolio model was constructed, with individual projects described with varying degrees of uncertainty detail. This provides a clear example of the methodology while demonstrating the relative importance of project specific uncertainties as these are translated into an aggregate corporate view. The simple analytic structure described in this paper may be scaled to represent much more complex uncertainty environments and more diverse assets as required. The value in properly capturing project specific uncertainties and maintaining these descriptions when assessing portfolio value and risks is quantified for the examples depicted.</jats:p

Crystal engineering: a case study using the 24 kDa fragment of the DNA gyrase B subunit from <i>Escherichia coli</i>

Site-directed mutagenesis was used to determine the efficacy of changing surface residues to improve crystal quality. Nine mutants of the 24 kDa fragment of the Escherichia coli DNA gyrase B subunit were produced, changing residues on the protein's surface. The mutations changed either the charge or the polarity of the wild-type amino acid. It was found that single amino-acid changes on the surface could have a dramatic effect on the crystallization properties of the protein and generally resulted in an improvement in the number of crystal-screen hits as well as an improvement in crystal quality. It is concluded that crystal engineering is a valuable tool for protein crystallography.</jats:p

Microseed matrix screening for optimization in protein crystallization: what have we learned?

Since the introduction of MMS in 2004, a number of reports (Obmolova et al., 2010a; Persson et al., 2010; Newman et al., 2011) have confirmed that it is a viable optimization alternative. It can produce high quality crystals from poor starting points that are not amenable to the classical optimization strategies. Here we review some recent developments in our own and others' work with MMS. On the basis of the successes from MMS, we offer recommendations for wider applications of MMS to crystallization problem

Organophotocatalytic radical-polar cross-coupling of styrene boronic acids and redox-active esters

Funding: AstraZeneca; EPSRC - EP/W007517; Leverhulme Trust - RF-2022-014.We report the development of a radical-polar cross-coupling reaction using styrene boronic acids and redox-active esters under organophotoredox catalysis. The reaction proceeds through a formal polarity-mismatched radical addition. The use of an organic photocatalyst enabled very low loadings of the electron-shuttle additive and accelerated reaction times compared to established processes. The scope of the reaction is explored, and the utility of the products is demonstrated.Publisher PDFPeer reviewe

Organophotocatalytic radical-polar cross-coupling of styrene boronic acids and redox-active esters

We report the development of a radical-polar cross-coupling reaction using styrene boronic acids and redox-active esters under organophotoredox catalysis. The reaction proceeds through a formal polarity-mismatched radical addition. The use of an organic photocatalyst enabled very low loadings of the electron-shuttle additive and accelerated reaction times compared to established processes. The scope of the reaction is explored, and the utility of the products is demonstrated

Crystal engineering: deletion mutagenesis of the 24 kDa fragment of the DNA gyrase B subunit from <i>Staphylococcus aureus</i>

The 24 kDa fragment of DNA gyrase B from Staphylococcus aureus was expressed in Escherichia coli and purified for crystallization. Crystals of the wild-type protein grew in the presence of cyclothialidine but proved difficult to reproduce. In order to improve the crystallization, the flexible regions of the protein were deleted by mutagenesis. The mutant proteins were analyzed by differential scanning calorimetry and the most stable mutants produced crystals. It was possible to reproducibly grow in the microbatch system single well defined crystals which belonged to the space group C2 and diffracted isotropically to approximately 2 Å resolution.</jats:p

Huperzia acerosa (Sw.) Holub.

Honduras, Lempira, Celaque National Park. LAT (14°32' N); LONG (88°40' W); ALT (2100). "Bosque secundario de cinco años de edad. Cerca el Campamento de Don Tómas.