The Pricing of Embedded Options in Real Estate Lease Contracts

Leases and rental agreements often have options attached or embedded in them. These options sometimes depend on a number of economic variables such as the consumer price index (CPI), a real estate index and/or the value of real estate underlying the agreement. The evaluation of these options often involves the solution or approximation to a partial differential equation (PDE). This study analyzes the appropriate PDEs which model the situation where the lessee is granted an option to either purchase the property or to renew the lease at a price (rent) indexed to the CPI or some other readily measured economic variable. The PDEs that result from the usual contingent claim asset-pricing framework are derived and numerically solved using the finite difference method with absorbing boundaries. The value of an embedded option to renew a five year lease on class A office space in each of the ternty-five markets for which the National Real Estate Index reports quarterly rental data is estimated. An evaluation of the model’s "Greeks" confirm that the model conforms to financial intuition which provides support for the accuracy of the estimates.

The Study of Intercommunion 1951-1971 : Evidence of a Hermeneutical Shift in Faith and Order

The thesis of this paper is that the approach to the problem of intercommunion taken by the Commission on Faith and Order demonstrates a foundational change in the hermeneutical approach taken by the Commission in doing theology. This conclusion is suggested as an answer to the question: What caused the shift in Faith and Order\u27s study and discussion of intercommunion from one that seeks agreement among doctrinal differences and difficulties to a pluralistic approach which embraces all perspectives as complimentary and mutually affirming? The significance of the hermeneutical shift is this: the seeming theological convergence on intercommunion has come at the expense of churches seeking agreement in truth. Differences in doctrine regarding the Lord\u27s Supper were once thought to be divisive and the challenge was seen to be how they may be corrected and overcome by churches together seeking that truth. Now, however, the differences in doctrine and practice, though they still exist between churches, are no longer held to be church dividing, at least from the perspective of the Commission on Faith and Order as it has developed its position on intercommunion

Taste Disagreements and Predicates of Personal Taste

In my dissertation, I explore the role of taste disagreements in the debate about the semantics of predicates of personal taste. Linguistic data derived from examples of gustatory disagreement often plays a major role in deciding the correct semantics of taste. I claim that, contrary to the trend in the recent literature, taste disagreements should not play any part in this debate. I argue that the data can be accommodated independently of the semantics by a theory of the purpose of “subjective” disagreements, such as taste disagreements. In support of this claim, I develop such a theory—one that includes an appeal to distinctively gustatory norms. I demonstrate how this theory can be applied equally well to the two major competing semantic theories—relativism and contextualism—to explain taste disagreements. If I am correct, this discovery represents a substantial contribution to the dialectic because it offers philosophers and linguists decisive motivation to discontinue their reliance on disagreement data in the debate about the semantics of taste

Pathways of Distinction Analysis: A New Technique for Multi–SNP Analysis of GWAS Data

Genome-wide association studies (GWAS) have become increasingly common due to advances in technology and have permitted the identification of differences in single nucleotide polymorphism (SNP) alleles that are associated with diseases. However, while typical GWAS analysis techniques treat markers individually, complex diseases (cancers, diabetes, and Alzheimers, amongst others) are unlikely to have a single causative gene. Thus, there is a pressing need for multi–SNP analysis methods that can reveal system-level differences in cases and controls. Here, we present a novel multi–SNP GWAS analysis method called Pathways of Distinction Analysis (PoDA). The method uses GWAS data and known pathway–gene and gene–SNP associations to identify pathways that permit, ideally, the distinction of cases from controls. The technique is based upon the hypothesis that, if a pathway is related to disease risk, cases will appear more similar to other cases than to controls (or vice versa) for the SNPs associated with that pathway. By systematically applying the method to all pathways of potential interest, we can identify those for which the hypothesis holds true, i.e., pathways containing SNPs for which the samples exhibit greater within-class similarity than across classes. Importantly, PoDA improves on existing single–SNP and SNP–set enrichment analyses, in that it does not require the SNPs in a pathway to exhibit independent main effects. This permits PoDA to reveal pathways in which epistatic interactions drive risk. In this paper, we detail the PoDA method and apply it to two GWAS: one of breast cancer and the other of liver cancer. The results obtained strongly suggest that there exist pathway-wide genomic differences that contribute to disease susceptibility. PoDA thus provides an analytical tool that is complementary to existing techniques and has the power to enrich our understanding of disease genomics at the systems-level

Casitas B-lineage lymphoma linker helix mutations found in myeloproliferative neoplasms affect conformation

Background: Casitas B-lineage lymphoma (Cbl or c-Cbl) is a RING ubiquitin ligase that negatively regulates protein tyrosine kinase (PTK) signalling. Phosphorylation of a conserved residue (Tyr371) on the linker helix region (LHR) between the substrate-binding and RING domains is required to ubiquitinate PTKs, thereby flagging them for degradation. This conserved Tyr is a mutational hotspot in myeloproliferative neoplasms. Previous studies have revealed that select point mutations in Tyr371 can potentiate transformation in cells and mice but not all possible mutations do so. To trigger oncogenic potential, Cbl Tyr371 mutants must perturb the LHR-substrate-binding domain interaction and eliminate PTK ubiquitination. Although structures of native and pTyr371-Cbl are available, they do not reveal how Tyr371 mutations affect Cbl’s conformation. Here, we investigate how Tyr371 mutations affect Cbl’s conformation in solution and how this relates to Cbl’s ability to potentiate transformation in cells. Results: To explore how Tyr371 mutations affect Cbl’s properties, we used surface plasmon resonance to measure Cbl mutant binding affinities for E2 conjugated with ubiquitin (E2–Ub), small angle X-ray scattering studies to investigate Cbl mutant conformation in solution and focus formation assays to assay Cbl mutant transformation potential in cells. Cbl Tyr371 mutants enhance E2–Ub binding and cause Cbl to adopt extended conformations in solution. LHR flexibility, RING domain accessibility and transformation potential are associated with the extent of LHR-substrate-binding domain perturbation affected by the chemical nature of the mutation. More disruptive mutants like Cbl Y371D or Y371S are more extended and the RING domain is more accessible, whereas Cbl Y371F mimics native Cbl in solution. Correspondingly, the only Tyr371 mutants that potentiate transformation in cells are those that perturb the LHR-substrate-binding domain interaction. Conclusions: c-Cbl’s LHR mutations are only oncogenic when they disrupt the native state and fail to ubiquitinate PTKs. These findings provide new insights into how LHR mutations deregulate c-Cbl

A general strategy for discovery of inhibitors and activators of RING and U-box E3 ligases with ubiquitin variants

RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2∼Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes

The nucleotide-binding site of Aquifex aeolicus LpxC

The structure of UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) in complex with UDP is reported. The complex allows for a description of how the enzyme recognizes and binds a nucleotide moiety and enables the construction of an LpxC-substrate model