Bayesian analysis of wildlife age-at-harvest data

SUMMARY: State and federal natural resource management agencies often collect age-structured harvest data. These data represent finite realizations of stochastic demographic and sampling processes and have long been used by biologists to infer population trends. However, different sources of data have been combined in ad hoc ways and these methods usually failed to incorporate sampling error. In this article, we propose a "hidden process" (or state-space) model for estimating abundance, survival, recovery rate, and recruitment from age-at-harvest data that incorporate both demographic and sampling stochasticity. To this end, a likelihood for age-at-harvest data is developed by embedding a population dynamics model within a model for the sampling process. Under this framework, the identification of abundance parameters can be achieved by conducting a joint analysis with an auxiliary data set. We illustrate this approach by conducting a Bayesian analysis of age-at-harvest and mark-recovery data from black bears (Ursus americanus) in Pennsylvania. Using a set of reasonable prior distributions, we demonstrate a substantial increase in precision when posterior summaries of abundance are compared to a bias-corrected Lincoln-Petersen estimator. Because demographic processes link consecutive abundance estimates, we also obtain a more realistic biological picture of annual changes in abundance. Because age-at-harvest data are often readily obtained, we argue that this type of analysis provides a valuable strategy for wildlife population monitoring.     

Substituted dipiperidine alcohols as potent CCR2 antagonists

The synthesis and biological evaluation of a series of substituted dipiperidine alcohols are described. Structure-activity relationship studies led to the discovery of potent CCR2 antagonists displaying IC(50) values in the nanomolar or subnanomolar range. The cinnamoyl compounds had higher binding affinities than the corresponding urea analogs.     

Bradykinin B1 receptor antagonists: an alpha-hydroxy amide with an improved metabolism profile

A series of carbo- and heterocyclic alpha-hydroxy amide-derived bradykinin B1 antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl alpha-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways.     

Design and synthesis of hydroxy-alkynoic acids and their methyl esters as novel activators of BK channels

Physiological and pharmacological agents that activate large conductance, voltage-, and calcium-gated potassium (BK) channels located in the smooth muscle are effective vasodilators. Thus, activators of smooth muscle BK channels may be potential therapeutic tools to treat cardiovascular disease associated with vasoconstriction and/or impaired dilation, such as cerebrovascular spasm and constriction. We previously showed that lithocholic acid (LC) and other cholane derivatives activated smooth muscle BK channels and, thus, caused endothelium-independent cerebral artery dilation. However, clinical use of these cholane derivatives could be limited by the actions of these steroids, such as elevation of intracellular calcium and induction of apoptosis. Using LC as template, we designed and synthesized a series of hydroxy-alkynoic acids and corresponding methyl esters, as putative, non-steroid BK channel activators. Indeed, the newly synthesized compounds effectively and reversibly activated rat cerebrovascular myocyte BK channel at concentrations similar to those found effective with LC. Among all the novel compounds tested, C-10 hydroxy-alkynoic acid methyl ester appears to be the most effective activator of vascular myocyte BK channels.     

Contrasting impacts of a native and an invasive exotic shrub on flood‐plain succession

Abstract. Question: How do Coriaria arborea, an N‐fixing native shrub, and Buddleja davidii, a non‐N‐fixing exotic shrub, affect N:P stoichiometry in plants and soils during early stages of primary succession on a flood‐plain? Location: Kowhai River Valley, northeast South Island, New Zealand. Methods: We measured soil and foliar nutrient concentrations, light levels, plant community composition and the above‐ground biomass of Coriaria and Buddleja in four successional stages: open, young, vigorous and mature. Results: Coriaria occurred at low density but dominated above‐ground biomass by the vigorous stage. Buddleja occurred at 5.3 ± 1.0 stems/m² in the young stage and reached a maximum biomass of 520–535 g.m^‐2 during the young and vigorous stages. Mineral soil N increased with above‐ground Coriaria biomass (r²= 0.45), but did not vary with Buddleja biomass. In contrast, soil P increased with Buddleja biomass (r²= 0.35), but not with Coriaria biomass. In early successional stages, 70–80% of the species present were exotic, but this declined to about 15% by the mature stage. Exotic plant species richness declined with increasing Coriaria biomass, but no other measures of diversity varied with either Coriaria or Buddleja biomass. Conclusion: These results demonstrate that Buddleja dominates early succession and accumulates P whereas Coriaria dominates later succession and accumulates N. A key ecosystem effect of the invasive exotic Buddleja is alteration of soil N:P stoichiometry.     

Microbial Responses to Microgravity and Other Low-Shear Environments

Microbial adaptation to environmental stimuli is essential for survival. While several of these stimuli have been studied in detail, recent studies have demonstrated an important role for a novel environmental parameter in which microgravity and the low fluid shear dynamics associated with microgravity globally regulate microbial gene expression, physiology, and pathogenesis. In addition to analyzing fundamental questions about microbial responses to spaceflight, these studies have demonstrated important applications for microbial responses to a ground-based, low-shear stress environment similar to that encountered during spaceflight. Moreover, the low-shear growth environment sensed by microbes during microgravity of spaceflight and during ground-based microgravity analogue culture is relevant to those encountered during their natural life cycles on Earth. While no mechanism has been clearly defined to explain how the mechanical force of fluid shear transmits intracellular signals to microbial cells at the molecular level, the fact that cross talk exists between microbial signal transduction systems holds intriguing possibilities that future studies might reveal common mechanotransduction themes between these systems and those used to sense and respond to low-shear stress and changes in gravitation forces. The study of microbial mechanotransduction may identify common conserved mechanisms used by cells to perceive changes in mechanical and/or physical forces, and it has the potential to provide valuable insight for understanding mechanosensing mechanisms in higher organisms. This review summarizes recent and future research trends aimed at understanding the dynamic effects of changes in the mechanical forces that occur in microgravity and other low-shear environments on a wide variety of important microbial parameters.     

Sample Size Determination for Grouped Exponential Observations: A Cost Function Approach

Calculating the required sample size for a desired power at a given type I error level, we often assume that we know the exact time of all subject responses whenever they occur during our study period. It is very common, however, in practice that we only monitor subjects periodically and, therefore, we know only whether responses occur or not during an interval. This paper includes a quantitative discussion of the effect resulting from data grouping or interval censoring on the required sample size when we have two treatment groups. Furthermore, with the goal of exploring the optimum in the number of subjects, the number of examinations per subject for test responses, and the total length of a study time period, this paper also provides a general guideline about how to determine these to minimize the total cost of a study for a desired power at a given α-level. A specified linear cost function that incorporates the costs of obtaining subjects, periodic examinations for test responses of subjects, and the total length of a study period, is assumed, primarily for illustrative purpose.     

In vivo effects of human dialyzable leukocyte lysate: III. Modulation of the spleen cell proliferative response to antigen by components of leukocyte dialysates and an initial characterization of an ampliative nucleoside

The augmentative effects of isolated components of human dialyzable leukocyte lysates upon the proliferative response to antigen were investigated. Sequential Sephadex G-25 and Bio-Gel P-4 chromatography separated five distinct fractions which, 24 hr after injection into Keyhole limpet hemacyanin (KLH)-sensitive mice, either augmented or suppressed the in vitro spleen cell proliferative response to KLH. An amplifier molecule was isolated from one of the augmentative fractions by high-pressure, reverse-phase liquid chromatography. Preliminary structural analysis of the amplifier component indicated a nucleoside structure, similar to—but possibly distinct from—thymidine.