567 research outputs found

    Analysis of brain adrenergic receptors in dopamine-ÎČ-hydroxylase knockout mice

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    The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-ÎČ-hydroxylase (DBH). Mice with a homozygous deletion of DBH (Dbh−/−) have a selective and complete absence of norepinephrine. The purpose of this study was to assess the expression of alpha-1, alpha-2 and beta adrenergic receptors (α1-AR, α2-AR and ÎČ-AR) in the postnatal absence of norepinephrine by comparing noradrenergic receptors in Dbh−/− mice with those in Dbh heterozygotes (Dbh+/−), which have normal levels of norepinephrine throughout life. The densities of α1-AR, α2-AR and ÎČ-AR were assayed with [3H]prazosin, [3H]RX21002 and [125I]-iodo-pindolol autoradiography, respectively. The α2-AR agonist high affinity state was examined with [125I]-paraiodoclonidine autoradiography and α2-AR functionality by α2-AR agonist-stimulated [35S] GTPÎłS autoradiography. The density of α1-AR in Dbh−/− mice was similar to Dbh+/− mice in most brain regions, with an up-regulation in the hippocampus. Modest decreases in α2-AR were found in septum, hippocampus and amygdala, but these were not reflected in α2-AR functionality. The density of ÎČ-AR was up-regulated to varying degrees in many brain regions of Dbh−/− mice compared to the heterozygotes. These findings indicate that regulation of noradrenergic receptors by endogenous norepinephrine depends on receptor type and neuroanatomical region

    Using Performance Forecasting to Accelerate Elasticity

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    Cloud computing facilitates dynamic resource provisioning. The automation of resource management, known as elasticity, has been subject to much research. In this context, monitoring of a running service plays a crucial role, and adjustments are made when certain thresholds are crossed. On such occasions, it is common practice to simply add or remove resources. In this paper we investigate how we can predict the performance of a service to dynamically adjust allocated resources based on predictions. In other words, instead of “repairing” because a threshold has been crossed, we attempt to stay ahead and allocate an optimized amount of resources in advance. To do so, we need to have accurate predictive models that are based on workloads. We present our approach, based on the Universal Scalability Law, and discuss initial experiments

    Developmental dynamics of two bipotent thymic epithelial progenitor types

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    T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. Here we combine scRNA-seq and a new CRISPR–Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity

    Phylogenetic and molecular analysis of hydrogen-producing green algae

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    A select set of microalgae are reported to be able to catalyse photobiological H2 production from water. Based on the model organism Chlamydomonas reinhardtii, a method was developed for the screening of naturally occurring H2-producing microalgae. By purging algal cultures with N2 in the dark and subsequent illumination, it is possible to rapidly induce photobiological H2 evolution. Using NMR spectroscopy for metabolic profiling in C. reinhardtii, acetate, formate, and ethanol were found to be key compounds contributing to metabolic variance during the assay. This procedure can be used to test algal species existing as axenic or mixed cultures for their ability to produce H2. Using this system, five algal isolates capable of H2 production were identified in various aquatic systems. A phylogenetic tree was constructed using ribosomal sequence data of green unicellular algae to determine if there were taxonomic patterns of H2 production. H2-producing algal species were seen to be dispersed amongst most clades, indicating an H2-producing capacity preceded evolution of the phylum Chlorophyta

    Habituated, Tolerant, or Salt-conditioned Mountain Goats and Human Safety

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    Interactions between humans and wildlife include a number of consumptive and non-consumptive forms. In some cases, the increased demand for wildlife viewing can precipitate new human–wildlife conflicts. Mountain goats (Oreamnos americanus; goats) are native to a number of North American mountain ranges from southeastern Alaska to southwestern Montana, USA. Goat habitat typically consists of steep terrain and cold weather habitats, which has left them particularly vulnerable to climate change. Their alpine environments also make them vulnerable to disturbance by aircraft and land-based motorized human activity. We reviewed and characterized situations in which goats in close proximity to humans on foot may become a nuisance or dangerous to people. We identify how such interactions might occur, focusing on the array of intensity observed in different settings. We summarize and evaluate interventions that have been attempted and may warrant additional research. Goats that tolerate people along hiking trails, perhaps through a habituation-like process, can typically be kept at a safe distance simply by shouting, clapping hands, or vigorous gestures. Goats that have learned to associate people with a salt reward (e.g., typically urine deposited on the ground, less frequently sweat obtained directly by licking) are more likely to be successfully hazed by tossing small stones, hitting the animal in the flank or rear. Salt-conditioned goats sometimes come within touching distance of humans; we strongly advise against prodding or poking these animals with sharp objects such as trekking poles. The recreating public that ventures into goat habitat is the ultimate source of these conflicts. Education, compliance, and possibly some infrastructure improvements can lessen the potential for conflicts and provide new and safer opportunities to view goats

    Spatial interactions in agent-based modeling

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    Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution of economic activities, - out of equilibrium. The Eurace@Unibi Model, an agent-based macroeconomic model with spatial structure, is used to illustrate the potential of such an approach for spatial policy analysis.Comment: 26 pages, 5 figures, 105 references; a chapter prepared for the book "Complexity and Geographical Economics - Topics and Tools", P. Commendatore, S.S. Kayam and I. Kubin, Eds. (Springer, in press, 2014

    Simple mindreading abilities predict complex theory of mind: developmental delay in autism spectrum disorders

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    Theory of Mind (ToM) is impaired in individuals with Autism Spectrum Disorders (ASD). The aims of this study were to: i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and ii) to assess if a ToM simple test known as Eyes-test could predict performance on the more advanced ToM task, i.e. Comic Strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD
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