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Does habitat stability structure intraspecific genetic diversity? It’s complicated...
Regional phylogeographic studies have long been conducted in the southeastern United States for a variety of species. With some exceptions, many of these studies focus on single species or single clades of organisms, and those considering multiple species tend to focus on deep historical breaks causing differentiation. However, in many species more recent factors may be influencing genetic diversity. To understand the roles of historic and contemporary processes in structuring genetic diversity, we reanalyzed existing genetic data from Southeast of North America using approaches gleaned from phylogeographic and landscape genetic literature that were implemented across species including AMOVAs, PCoAs, Species Distribution Modelling, and tests of isolation by distance, environment, and habitat instability. Genetic variance was significantly partitioned by ecoregions, watersheds, and across phylogeographic breaks in the majority of species. Similarly, genetic variation was significantly associated with some combination of geographic or environmental distance or habitat instability in most species. Patterns of genetic variation were largely idiosyncratic across species. While habitat instability over time is significantly correlated with genetic diversity in some species, it appears generally less important than isolation by geographic or environmental distance. Our results suggest that many factors, both historical and contemporary, impact genetic diversity within a species, and more so, that these patterns aren’t always similar in closely related species. This supports the importance of species- specific factors and cautions against assumptions that closely related species will respond to historical and contemporary forces in similar ways
Gas Condensation in the Galactic Halo
Using adaptive mesh refinement (AMR) hydrodynamic simulations of vertically
stratified hot halo gas, we examine the conditions under which clouds can form
and condense out of the hot halo medium to potentially fuel star formation in
the gaseous disk. We find that halo clouds do not develop from linear isobaric
perturbations. This is a regime where the cooling time is longer than the
Brunt-Vaisala time, confirming previous linear analysis. We extend the analysis
into the nonlinear regime by considering mildly or strongly nonlinear
perturbations with overdensities up to 100, also varying the initial height,
the cloud size, and the metallicity of the gas. Here, the result depends on the
ratio of cooling time to the time required to accelerate the cloud to the sound
speed (similar to the dynamical time). If the ratio exceeds a critical value
near unity, the cloud is accelerated without further cooling and gets disrupted
by Kelvin-Helmholtz and/or Rayleigh-Taylor instabilities. If it is less than
the critical value, the cloud cools and condenses before disruption. Accreting
gas with overdensities of 10-20 is expected to be marginally unstable; the
cooling fraction will depend on the metallicity, the size of the incoming
cloud, and the distance to the galaxy. Locally enhanced overdensities within
cold streams have a higher likelihood of cooling out. Our results have
implications on the evolution of clouds seeded by cold accretion that are
barely resolved in current cosmological hydrodynamic simulations and absorption
line systems detected in galaxy halos.Comment: 13 pages, 8 figures, submitted to Ap
The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs
Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3
Identification of ultra low-risk patients following primary angioplasty for acute myocardial infarction
715-2 A Prospective, Randomized Trial Evaluating the Prophylactic Use of Balloon Pumping in High Risk Myocardial Infarction Patients: PAMI-2
Myocardial infarction (MI) patients with advanced age, multivessel disease or ventricular dysfunction continue to have a poor prognosis despite reperfusion therapy. Furthermore, the majority of deaths from MI occur within the first 48 hours, thus risk stratification and therapeutic interventions ideally should occur acutely. The PAMI-2 study has prospectively evaluated the hypotheses that 1) emergency catheterization with primary PTCA may allow acute risk stratification and 2) clinical outcome, ventricular function and infarct vessel patency will be improved by balloon pumping in patients identified to be high risk. MI patients who presented 0–12 hrs underwent emergency catheterization and PTCA and were stratified as high risk if one of the following was present: age>70 yrs, vein graft occlusion, 3 vessel disease, ejection fraction <45%, suboptimal PTCA result or if malignant arrhythmias persisted post PTCA. High risk patients were randomized to receive or not receive an intra aortic balloon pump (IABP) for 48 hrs. Catheterization was repeated at day 7 to determine infarct vessel patency and improvement in ventricular function. At 6 weeks a rest and exercise radionuclide ventriculogram was performed. To date, 320 patients have been enrolled, 175 of which have complete data available for analysis. The reasons for high risk status include: advanced age 38%, poor LV function 55%, 3 vessel disease 37%, vein graft occlusion 6%, suboptimal PTCA 9%, and arrhythmias 5%. Despite the high risk status, in-hospital outcomes have been favorable: death 2.9%, recurrent MI 5.8%, stroke 1.2%, angiographic reocclusion 5.8%, heart failure 19.1% and combined events 26.6%. Thus “high risk” patients treated with primary PTCA±balloon pumping appear to have a good prognosis. Whether the improved outcome is due to balloon pump support or simply due to aggressive mechanical revascularization will be determined in the entire cohort by March 1995
Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle
We reconsider the problem of the stability of the thermohaline circulation as
described by a two-dimensional Boussinesq model with mixed boundary conditions.
We determine how the stability properties of the system depend on the intensity
of the hydrological cycle. We define a two-dimensional parameters' space
descriptive of the hydrology of the system and determine, by considering
suitable quasi-static perturbations, a bounded region where multiple equilibria
of the system are realized. We then focus on how the response of the system to
finite-amplitude surface freshwater forcings depends on their rate of increase.
We show that it is possible to define a robust separation between slow and fast
regimes of forcing. Such separation is obtained by singling out an estimate of
the critical growth rate for the anomalous forcing, which can be related to the
characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy
Hydrodynamical adaptive mesh refinement simulations of turbulent flows - I. Substructure in a wind
The problem of the resolution of turbulent flows in adaptive mesh refinement
(AMR) simulations is investigated by means of 3D hydrodynamical simulations in
an idealised setup, representing a moving subcluster during a merger event. AMR
simulations performed with the usual refinement criteria based on local
gradients of selected variables do not properly resolve the production of
turbulence downstream of the cluster. Therefore we apply novel AMR criteria
which are optimised to follow the evolution of a turbulent flow. We demonstrate
that these criteria provide a better resolution of the flow past the
subcluster, allowing us to follow the onset of the shear instability, the
evolution of the turbulent wake and the subsequent back-reaction on the
subcluster core morphology. We discuss some implications for the modelling of
cluster cold fronts.Comment: 11 pages, 14 figures. Small changes to match the version accepted by
MNRA
Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention
Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target
Simulation techniques for cosmological simulations
Modern cosmological observations allow us to study in great detail the
evolution and history of the large scale structure hierarchy. The fundamental
problem of accurate constraints on the cosmological parameters, within a given
cosmological model, requires precise modelling of the observed structure. In
this paper we briefly review the current most effective techniques of large
scale structure simulations, emphasising both their advantages and
shortcomings. Starting with basics of the direct N-body simulations appropriate
to modelling cold dark matter evolution, we then discuss the direct-sum
technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and
the tree algorithms. Simulations of baryonic matter in the Universe often use
hydrodynamic codes based on both particle methods that discretise mass, and
grid-based methods. We briefly describe Eulerian grid methods, and also some
variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science
Reviews, special issue "Clusters of galaxies: beyond the thermal view",
Editor J.S. Kaastra, Chapter 12; work done by an international team at the
International Space Science Institute (ISSI), Bern, organised by J.S.
Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
Plasmodium falciparum serology: A comparison of two protein production methods for analysis of antibody responses by protein microarray.
The evaluation of protein antigens as putative serologic biomarkers of infection has increasingly shifted to high-throughput, multiplex approaches such as the protein microarray. In vitro transcription/translation (IVTT) systems-a similarly high-throughput protein expression method-are already widely utilised in the production of protein microarrays, though purified recombinant proteins derived from more traditional whole cell based expression systems also play an important role in biomarker characterisation. Here we have performed a side-by-side comparison of antigen-matched protein targets from an IVTT and purified recombinant system, on the same protein microarray. The magnitude and range of antibody responses to purified recombinants was found to be greater than that of IVTT proteins, and responses between targets from different expression systems did not clearly correlate. However, responses between amino acid sequence-matched targets from each expression system were more closely correlated. Despite the lack of a clear correlation between antigen-matched targets produced in each expression system, our data indicate that protein microarrays produced using either method can be used confidently, in a context dependent manner, though care should be taken when comparing data derived from contrasting approaches
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