604 research outputs found
Using density surface models to estimate spatio-temporal changes in population densities and trend
Funding â Centre for Research into Ecological and Environmental Modelling, University of St Andrews and U.S. Geological Survey provided funding for this analysis through a studentship to RJC.Precise measures of population abundance and trend are needed for species conservation; these are most difficult to obtain for rare and rapidly changing populations. We compare uncertainty in densities estimated from spatioâtemporal models with that from standard designâbased methods. Spatioâtemporal models allow us to target priority areas where, and at times when, a population may most benefit. Generalised additive models were fitted to a 31âyear time series of pointâtransect surveys of an endangered Hawaiian forest bird, the Hawai'i âÄkepa Loxops coccineus. This allowed us to estimate bird densities over space and time. We used two methods to quantify uncertainty in density estimates from the spatioâtemporal model: the delta method (which assumes independence between detection and distribution parameters) and a variance propagation method. With the delta method we observed a 52% decrease in the width of the designâbased 95% confidence interval (CI), while we observed a 37% decrease in CI width when propagating the variance. We mapped bird densities as they changed across space and time, allowing managers to evaluate management actions. Integrating detection function modelling with spatioâtemporal modelling exploits survey data more efficiently by producing finerâgrained abundance estimates than are possible with designâbased methods as well as producing more precise abundance estimates. Modelâbased approaches require switching from making assumptions about the survey design to assumptions about bird distribution. Such a switch warrants carefully considered. In this case the modelâbased approach benefits conservation planning through improved management efficiency and reduced costs by taking into account both spatial shifts and temporal changes in population abundance and distribution.Publisher PDFPeer reviewe
Differential Photoelectron Holography: A New Approach for Three-Dimensional Atomic Imaging
We propose differential holography as a method to overcome the long-standing
forward-scattering problem in photoelectron holography and related techniques
for the three-dimensional imaging of atoms. Atomic images reconstructed from
experimental and theoretical Cu 3p holograms from Cu(001) demonstrate that this
method suppresses strong forward-scattering effects so as to yield more
accurate three-dimensional images of side- and back-scattering atoms.Comment: revtex, 4 pages, 2 figure
A realistic two-lane traffic model for highway traffic
A two-lane extension of a recently proposed cellular automaton model for
traffic flow is discussed. The analysis focuses on the reproduction of the lane
usage inversion and the density dependence of the number of lane changes. It is
shown that the single-lane dynamics can be extended to the two-lane case
without changing the basic properties of the model which are known to be in
good agreement with empirical single-vehicle data. Therefore it is possible to
reproduce various empirically observed two-lane phenomena, like the
synchronization of the lanes, without fine-tuning of the model parameters
Holographic analysis of diffraction structure factors
We combine the theory of inside-source/inside-detector x-ray fluorescence
holography and Kossel lines/x ray standing waves in kinematic approximation to
directly obtain the phases of the diffraction structure factors. The influence
of Kossel lines and standing waves on holography is also discussed. We obtain
partial phase determination from experimental data obtaining the sign of the
real part of the structure factor for several reciprocal lattice vectors of a
vanadium crystal.Comment: 4 pages, 3 figures, submitte
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How important are post-tropical cyclones for European windstorm risk?
Post-tropical cyclones (PTCs) extend many hazards associated with tropical cyclones (TCs) to the mid-latitudes. Despite recent high-impact cases affecting Europe such as Ophelia, little research has been done to characterize the risk of PTCs. Here we compare the climatologies and intensity distributions of mid-latitude cyclones (MLCs) and PTCs in the North Atlantic and Europe by tracking cyclones in the ERA5 reanalysis. Considering hurricane-season cyclones impacting Northern Europe, PTCs show a significantly higher mean maximum intensity than MLCs, but make only a small contribution to total windstorm risk. Our results show that a disproportionately large fraction of high-intensity cyclones impacting Europe during hurricane season are PTCs. The fraction of PTCs impacting N Europe with storm-force (>25ms-1) winds is approximately ten times higher than for MLCs. Less than 1% of cyclones impacting Northern Europe are identified to be PTCs. This rises to 8.8% when considering cyclones which impact with storm-force winds
In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly effect" described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131-1136], whereby through apparently the same underlying mechanism, the removal of a protein's activity from a cell can have widely divergent effects depending on the time course of that removal.S.J.B. was supported by an A.J. Clark Studentship from the British Pharmacological Society, A.D. by Sidney Sussex College, the Cambridge Overseas Trust and the SÀid Foundation, and J.H.C by the MRC (Grant RG64071).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Proceedings of the National Academy of Sciences (PNAS)
Role of anion exchangers in Cl- and HCO3- secretion by the human airway epithelial cell line Calu-3
Despite the importance of airway surface liquid pH in the lung's defenses against infection, the mechanism of airway HCO3- secretion remains unclear. Our aim was to assess the contribution of apical and basolateral Cl-/HCO3- exchangers to Cl- and HCO3- transport in the Calu-3 cell line, derived from human airway submucosal glands. Changes in intracellular pH (pH(i)) were measured following substitution of Cl- with gluconate. Apical Cl- substitution led to an alkalinization in forskolin-stimulated cells, indicative of Cl-/HCO3- exchange. This was unaffected by the anion exchange inhibitor DIDS but inhibited by the CFTR blocker CFTRinh-172, suggesting that the HCO3- influx might occur via CFTR, rather than a solute carrier family 26 (SLC26) exchanger, as recently proposed. The anion selectivity of the recovery process more closely resembled that of CFTR than an SLC26 exchanger, and quantitative RT-PCR showed only low levels of SLC26 exchanger transcripts relative to CFTR and anion exchanger 2 (AE2). For pHi to rise to observed values (similar to 7.8) through HCO3- entry via CFTR, the apical membrane potential must reverse to at least + 20 mV following Cl- substitution; this was confirmed by perforated-patch recordings. Substitution of basolateral Cl- evoked a DIDS-sensitive alkalinization, attributed to Cl-/HCO3- exchange via AE2. This appeared to be abolished in forskolin-stimulated cells but was unmasked by blocking apical efflux of HCO3- via CFTR. We conclude that Calu-3 cells secrete HCO3- predominantly via CFTR, and, contrary to previous reports, the basolateral anion exchanger AE2 remains active during stimulation, providing an important pathway for basolateral Cl- uptake
An asymptotic form of the reciprocity theorem with applications in x-ray scattering
The emission of electromagnetic waves from a source within or near a
non-trivial medium (with or without boundaries, crystalline or amorphous, with
inhomogeneities, absorption and so on) is sometimes studied using the
reciprocity principle. This is a variation of the method of Green's functions.
If one is only interested in the asymptotic radiation fields the generality of
these methods may actually be a shortcoming: obtaining expressions valid for
the uninteresting near fields is not just a wasted effort but may be
prohibitively difficult. In this work we obtain a modified form the reciprocity
principle which gives the asymptotic radiation field directly. The method may
be used to obtain the radiation from a prescribed source, and also to study
scattering problems. To illustrate the power of the method we study a few
pedagogical examples and then, as a more challenging application we tackle two
related problems. We calculate the specular reflection of x rays by a rough
surface and by a smoothly graded surface taking polarization effects into
account. In conventional treatments of reflection x rays are treated as scalar
waves, polarization effects are neglected. This is a good approximation at
grazing incidence but becomes increasingly questionable for soft x rays and UV
at higher incidence angles.
PACs: 61.10.Dp, 61.10.Kw, 03.50.DeComment: 19 pages, 4 figure
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Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy.
Redundancy and compensation provide robustness to biological systems but may contribute to therapy resistance. Both tumor-associated macrophages (TAMs) and Foxp3+ regulatory T (Treg) cells promote tumor progression by limiting antitumor immunity. Here we show that genetic ablation of CSF1 in colorectal cancer cells reduces the influx of immunosuppressive CSF1R+ TAMs within tumors. This reduction in CSF1-dependent TAMs resulted in increased CD8+ T cell attack on tumors, but its effect on tumor growth was limited by a compensatory increase in Foxp3+ Treg cells. Similarly, disruption of Treg cell activity through their experimental ablation produced moderate effects on tumor growth and was associated with elevated numbers of CSF1R+ TAMs. Importantly, codepletion of CSF1R+ TAMs and Foxp3+ Treg cells resulted in an increased influx of CD8+ T cells, augmentation of their function, and a synergistic reduction in tumor growth. Further, inhibition of Treg cell activity either through systemic pharmacological blockade of PI3KÎŽ, or its genetic inactivation within Foxp3+ Treg cells, sensitized previously unresponsive solid tumors to CSF1R+ TAM depletion and enhanced the effect of CSF1R blockade. These findings identify CSF1R+ TAMs and PI3KÎŽ-driven Foxp3+ Treg cells as the dominant compensatory cellular components of the immunosuppressive tumor microenvironment, with implications for the design of combinatorial immunotherapies.D. Gyori was funded by a research grant from Karus Therapeutics. E.L. Lim was supported by a Yousef Jameel Scholarship (Cambridge Trust). R. Roychoudhuri and K. Okkenhaug received institute support from Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000 -C0407, -C0409, -C0427 and -C0428). K. Okkenhaug was also supported by Wellcome Trust grant 095198/Z/10/Z. L.R. Stephens and P.T. Hawkins were supported by and institute grant from the BBSRC (BB/J004456/1). R. Roychoudhuri is supported by the Wellcome Trust/Royal Society (Grant 105663/Z/14/Z), the UK Biotechnology and Biological Sciences Research Council (Grant BB/N007794/1), and Cancer Research UK (Grant C52623/A22597)
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