Decision Analysis with Geographically Varying Outcomes: Preference Models and Illustrative Applications

DRMI Working Paper SeriesThe series is intended to convey the preliminary results of [DRMI] ongoing research. The research described in these papers is preliminary and has not completed the usual review process for Institute publications. We welcome feedback from readers and encourage you to convey your comments and criticisms directly to the authors

Multiple attribute scenarios, bounded probabilities, and threats of nuclear theft

A method is presented for developing descriptions of future scenarios and using expert judgment to assess bounds on the probabilities of these scenarios. Multiple attributes are used to describe the important features of the scenarios, and the scenarios are defined as collections of different possible levels of the attributes. Experts assess either numerical values or bounds on various unconditional and conditional probabilities for different attribute levels. These are used to establish constraints for a series of linear programs which are solved to determine the highest and lowest possible probabilities for each scenario. An application is presented to the assessment of potential threats against nuclear material safeguards systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23794/1/0000032.pd

First-Step Mutations for Adaptation at Elevated Temperature Increase Capsid Stability in a Virus

The relationship between mutation, protein stability and protein function plays a central role in molecular evolution. Mutations tend to be destabilizing, including those that would confer novel functions such as host-switching or antibiotic resistance. Elevated temperature may play an important role in preadapting a protein for such novel functions by selecting for stabilizing mutations. In this study, we test the stability change conferred by single mutations that arise in a G4-like bacteriophage adapting to elevated temperature. The vast majority of these mutations map to interfaces between viral coat proteins, suggesting they affect protein-protein interactions. We assess their effects by estimating thermodynamic stability using molecular dynamic simulations and measuring kinetic stability using experimental decay assays. The results indicate that most, though not all, of the observed mutations are stabilizing

A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document

A comparative perspective on the evolution of tamarin and marmoset social systems

Tamarins and marmosets (callitrichids) present an unusual opportunity for study of the determinants of primate social systems, because both the mating and infant care patterns of callitrichids are variable, even within individual populations. In this paper, I briefly describe three characteristics of callitrichid social systems that distinguish them from most other primates: extensive male parental care, helping by nonreproductive individuals, and variable mating patterns. I then discuss the evolution of these characteristics and of the frequent twinning exhibited by callitrichids. I suggest that an ancestor of modern callitrichids gave birth to a single offspring at a time, mated monogamously, and had significant paternal care. The idea that males of this ancestral form must have provided paternal care, even though only single infants were born, derives from a comparison of litter/mother weight ratios in modern primate species. Twinning perhaps then evolved because of a combination of dwarfing in the callitrichid lineage, leading to higher litter/mother weight ratios, and a high infant mortality rate, and because the extensive paternal care already present facilitated the raising of twins. I propose that the helping behavior of older offspring may have coevolved with twinning, because helpers would have increased the chances of survival of twins, and the presence of twins would have increased the benefits of helping. Finally, the high costs of raising twins and the variability of group compositions, especially the fact that some groups would not have had older offspring to serve as helpers, may have selected for facultative polyandry in saddle-back tamarins ( Saguinus fuscicollis ) and perhaps in other callitrichid species. Both helping and cooperative polyandry have been extensively studied in bird species, and I apply some of the conclusions of these studies to the discussion of the evolution of callitrichid social systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44556/1/10764_2005_Article_BF02193696.pd

The effect of dietary restriction on reproduction: a meta-analytic perspective

Background: Dietary restriction (DR), a reduction in the amount of food or particular nutrients eaten, is the most consistent environmental manipulation to extend lifespan and protect against age related diseases. Current evolutionary theory explains this effect as a shift in the resolution of the trade-off between lifespan and reproduction. However, recent studies have questioned the role of reproduction in mediating the effect of DR on longevity and no study has quantitatively investigated the effect of DR on reproduction across species. Results: Here we report a comprehensive comparative meta-analysis of the effect of DR on reproduction. In general, DR reduced reproduction across taxa, but several factors moderated this effect. The effect of DR on reproduction was greater in well-studied model species (yeast, nematode worms, fruit flies and rodents) than non-model species. This mirrors recent results for longevity and, for reproduction, seems to result from a faster rate of decline with decreasing resources in model species. Our results also suggested that not all reproductive traits are affected equally by DR. High and moderate cost reproductive traits suffered a significant reduction with DR, but low cost traits, such as ejaculate production, did not. Although the effect of DR on reproduction was stronger in females than males, this sex difference reduced to near zero when accounting for other co-factors such as the costliness of the reproductive trait. Thus, sex differences in the effect of DR on longevity may be due to a failure to expose males to as complete a range of the costs of reproduction as females. Conclusions: We suggest that to better understand the generality of the effect of DR, future studies should attempt to address the cause of the apparent model species bias and ensure that individuals are exposed to as many of the costs of reproduction as possible. Furthermore, our meta-analytic approach reveals a general shortage of DR studies that record reproduction, particularly in males, as well as a lack of direct side-by-side comparisons of the effect of DR on males and females

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations