Permanents, Pfaffian orientations, and even directed circuits

Given a 0-1 square matrix A, when can some of the 1's be changed to -1's in such a way that the permanent of A equals the determinant of the modified matrix? When does a real square matrix have the property that every real matrix with the same sign pattern (that is, the corresponding entries either have the same sign or are both zero) is nonsingular? When is a hypergraph with n vertices and n hyperedges minimally nonbipartite? When does a bipartite graph have a "Pfaffian orientation"? Given a digraph, does it have no directed circuit of even length? Given a digraph, does it have a subdivision with no even directed circuit? It is known that all of the above problems are equivalent. We prove a structural characterization of the feasible instances, which implies a polynomial-time algorithm to solve all of the above problems. The structural characterization says, roughly speaking, that a bipartite graph has a Pfaffian orientation if and only if it can be obtained by piecing together (in a specified way) planar bipartite graphs and one sporadic nonplanar bipartite graph.Comment: 47 pages, published versio

Risk measurement: an introduction to value at risk

This paper is a self-contained introduction to the concept and methodology of "value at risk," which is a new tool for measuring an entity's exposure to market risk. We explain the concept of value at risk, and then describe in detail the three methods for computing it: historical simulation; the variance-covariance method; and Monte Carlo or stochastic simulation. We then discuss the advantages and disadvantages of the three methods for computing value at risk. Finally, we briefly describe some alternative measures of market risk.Risk and Uncertainty,

Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa

Optimization of resource allocation can explain the temporal dynamics and honesty of sexual signals

In species in which males are free to dynamically alter their allocation to sexual signaling over the breeding season, the optimal investment in signaling should depend on both a male’s state and the level of competition he faces at any given time. We developed a dynamic optimization model within a game‐theoretical framework to explore the resulting signaling dynamics at both individual and population levels and tested two key model predictions with empirical data on three‐spined stickleback (Gasterosteus aculeatus) males subjected to dietary manipulation (carotenoid availability): (1) fish in better nutritional condition should be able to maintain their signal for longer over the breeding season, resulting in an increasingly positive correlation between nutritional status and signal (i.e., increasing signal honesty), and (2) female preference for more ornamented males should thus increase over the breeding season. Both predictions were supported by the experimental data. Our model shows how such patterns can emerge from the optimization of resource allocation to signaling in a competitive situation. The key determinants of the honesty and dynamics of sexual signaling are the condition dependency of male survival, the initial frequency distribution of nutritional condition in the male population, and the cost of signaling

Modelling individual variability in cognitive development

Investigating variability in reasoning tasks can provide insights into key issues in the study of cognitive development. These include the mechanisms that underlie developmental transitions, and the distinction between individual differences and developmental disorders. We explored the mechanistic basis of variability in two connectionist models of cognitive development, a model of the Piagetian balance scale task (McClelland, 1989) and a model of the Piagetian conservation task (Shultz, 1998). For the balance scale task, we began with a simple feed-forward connectionist model and training patterns based on McClelland (1989). We investigated computational parameters, problem encodings, and training environments that contributed to variability in development, both across groups and within individuals. We report on the parameters that affect the complexity of reasoning and the nature of ‘rule’ transitions exhibited by networks learning to reason about balance scale problems. For the conservation task, we took the task structure and problem encoding of Shultz (1998) as our base model. We examined the computational parameters, problem encodings, and training environments that contributed to variability in development, in particular examining the parameters that affected the emergence of abstraction. We relate the findings to existing cognitive theories on the causes of individual differences in development

Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions

Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis

Preclinical osteoarthritis (OA) models are often employed in studies investigating disease-modifying OA drugs (DMOADs). In this study we present a comprehensive, longitudinal evaluation of OA pathogenesis in a rat model of OA, including histologic and biochemical analyses of articular cartilage degradation and assessment of subchondral bone sclerosis. Male Sprague-Dawley rats underwent joint destabilization surgery by anterior cruciate ligament transection and partial medial meniscectomy. The contralateral joint was evaluated as a secondary treatment, and sham surgery was performed in a separate group of animals (controls). Furthermore, the effects of walking on a rotating cylinder (to force mobilization of the joint) on OA pathogenesis were assessed. Destabilization-induced OA was investigated at several time points up to 20 weeks after surgery using Osteoarthritis Research Society International histopathology scores, in vivo micro-computed tomography (CT) volumetric bone mineral density analysis, and biochemical analysis of type II collagen breakdown using the CTX II biomarker. Expression of hypertrophic chondrocyte markers was also assessed in articular cartilage. Cartilage degradation, subchondral changes, and subchondral bone loss were observed as early as 2 weeks after surgery, with considerable correlation to that seen in human OA. We found excellent correlation between histologic changes and micro-CT analysis of underlying bone, which reflected properties of human OA, and identified additional molecular changes that enhance our understanding of OA pathogenesis. Interestingly, forced mobilization exercise accelerated OA progression. Minor OA activity was also observed in the contralateral joint, including proteoglycan loss. Finally, we observed increased chondrocyte hypertrophy during pathogenesis. We conclude that forced mobilization accelerates OA damage in the destabilized joint. This surgical model of OA with forced mobilization is suitable for longitudinal preclinical studies, and it is well adapted for investigation of both early and late stages of OA. The time course of OA progression can be modulated through the use of forced mobilization