Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen

The weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single Vk1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps. Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR

A national scale inventory of resource provision for biodiversity within domestic gardens

The human population is increasingly disconnected from nature due to urbanisation. To counteract this phenomenon, the UK government has been actively promoting wildlife gardening. However, the extent to which such activities are conducted and the level of resource provision for biodiversity (e.g., food and nesting sites) within domestic gardens remains poorly documented. Here we generate estimates for a selection of key resources provided within gardens at a national scale, using 12 survey datasets gathered across the UK. We estimate that 22.7 million households (87% of homes) have access to a garden. Average garden SiZe is 190 m(2), extrapolating to a total area of 432,924 ha. Although substantial, this coverage is still an order of magnitude less than that of statutory protected areas. Approximately 12.6 million (48%) households provide supplementary food for birds, 7.4 million of which specifically use bird feeders. Similarly, there are a minimum of 4.7 million nest boxes within gardens. These figures equate to one bird feeder for every nine potentially feeder-using birds in the UK, and at least one nest box for every six breeding pairs of cavity nesting birds. Gardens also contain 2.5-3.5 million ponds and 28.7 million trees, which is just under a quarter of all trees occurring outside woodlands. Ongoing urbanisation, characterised by increased housing densities, is inevitable throughout the UK and elsewhere. The important contribution domestic gardens make to the green space infrastructure in residential areas must be acknowledged, as their reduction will impact biodiversity conservation, ecosystem services, and the well-being of the human population

Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme

The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium. This study examines the potential for Foxd1-positive cells of the kidney and lung to give rise to endothelial progenitors. We utilized immunofluorescence (IF) and fluorescence-activated cell sorting (FACS) to co-label Foxd1-expressing cells (including permanently lineage-tagged cells) with endothelial markers in embryonic and postnatal mice. We also cultured FACsorted Foxd1-positive cells, performed in vitro endothelial cell tubulogenesis assays and examined for endocytosis of acetylated low-density lipoprotein (Ac-LDL), a functional assay for endothelial cells. Immunofluorescence and FACS revealed that a subset of Foxd1-positive cells from kidney and lung co-expressed endothelial cell markers throughout embryogenesis. In vitro, cultured embryonic Foxd1-positive cells were able to differentiate into tubular networks that expressed endothelial cell markers and were able to endocytose Ac-LDL. IF and FACS in both the kidney and lung revealed that lineage-tagged Foxd1-positive cells gave rise to a significant portion of the endothelium in postnatal mice. In the kidney, the stromal-derived cells gave rise to a portion of the peritubular capillary endothelium, but not of the glomerular or large vessel endothelium. These findings reveal the heterogeneity of endothelial cell lineages; moreover, Foxd1-positive mesenchymal cells of the developing kidney and lung are a source of endothelial progenitors that are likely critical to patterning the vasculature. © 2013 Sims-Lucas et al

Cartan subalgebras in C*-algebras of Hausdorff etale groupoids

The reduced $C^*$-algebra of the interior of the isotropy in any Hausdorff \'etale groupoid $G$ embeds as a $C^*$-subalgebra $M$ of the reduced $C^*$-algebra of $G$. We prove that the set of pure states of $M$ with unique extension is dense, and deduce that any representation of the reduced $C^*$-algebra of $G$ that is injective on $M$ is faithful. We prove that there is a conditional expectation from the reduced $C^*$-algebra of $G$ onto $M$ if and only if the interior of the isotropy in $G$ is closed. Using this, we prove that when the interior of the isotropy is abelian and closed, $M$ is a Cartan subalgebra. We prove that for a large class of groupoids $G$ with abelian isotropy---including all Deaconu--Renault groupoids associated to discrete abelian groups---$M$ is a maximal abelian subalgebra. In the specific case of $k$-graph groupoids, we deduce that $M$ is always maximal abelian, but show by example that it is not always Cartan.Comment: 14 pages. v2: Theorem 3.1 in v1 incorrect (thanks to A. Kumjain for pointing out the error); v2 shows there is a conditional expectation onto $M$ iff the interior of the isotropy is closed. v3: Material (including some theorem statements) rearranged and shortened. Lemma~3.5 of v2 removed. This version published in Integral Equations and Operator Theor

Creativity and Autonomy in Swarm Intelligence Systems

This work introduces two swarm intelligence algorithms -- one mimicking the behaviour of one species of ants (\emph{Leptothorax acervorum}) foraging (a `Stochastic Diffusion Search', SDS) and the other algorithm mimicking the behaviour of birds flocking (a `Particle Swarm Optimiser', PSO) -- and outlines a novel integration strategy exploiting the local search properties of the PSO with global SDS behaviour. The resulting hybrid algorithm is used to sketch novel drawings of an input image, exploliting an artistic tension between the local behaviour of the `birds flocking' - as they seek to follow the input sketch - and the global behaviour of the `ants foraging' - as they seek to encourage the flock to explore novel regions of the canvas. The paper concludes by exploring the putative `creativity' of this hybrid swarm system in the philosophical light of the `rhizome' and Deleuze's well known `Orchid and Wasp' metaphor

A framework for space-efficient string kernels

String kernels are typically used to compare genome-scale sequences whose length makes alignment impractical, yet their computation is based on data structures that are either space-inefficient, or incur large slowdowns. We show that a number of exact string kernels, like the $k$-mer kernel, the substrings kernels, a number of length-weighted kernels, the minimal absent words kernel, and kernels with Markovian corrections, can all be computed in $O(nd)$ time and in $o(n)$ bits of space in addition to the input, using just a $\mathtt{rangeDistinct}$ data structure on the Burrows-Wheeler transform of the input strings, which takes $O(d)$ time per element in its output. The same bounds hold for a number of measures of compositional complexity based on multiple value of $k$, like the $k$-mer profile and the $k$-th order empirical entropy, and for calibrating the value of $k$ using the data

A measurement system for vertical seawater profiles close to the air–sea interface

This paper describes a near-surface ocean profiler, which has been designed to precisely measure vertical gradients in the top 10 m of the ocean. Variations in the depth of seawater collection are minimized when using the profiler compared to conventional CTD/rosette deployments. The profiler consists of a remotely operated winch mounted on a tethered yet free-floating buoy, which is used to raise and lower a small frame housing sensors and inlet tubing. Seawater at the inlet depth is pumped back to the ship for analysis. The profiler can be used to make continuous vertical profiles or to target a series of discrete depths. The profiler has been successfully deployed during wind speeds up to 10 m s−1 and significant wave heights up to 2 m. We demonstrate the potential of the profiler by presenting measured vertical profiles of the trace gases carbon dioxide and dimethylsulfide. Trace gas measurements use an efficient microporous membrane equilibrator to minimize the system response time. The example profiles show vertical gradients in the upper 5 m for temperature, carbon dioxide and dimethylsulfide of 0.15 °C, 4 µatm and 0.4 nM respectively

Photofission and Quasi-Deuteron-Nuclear State as Mixing of Bosons and Fermions

The empirical-phenomenological quasi-deuteron photofission description is theoretically justified within the semiclassical, intermediate statistics model. The transmutational fermion (nucleon) - boson (quasi-deuteron) potential plays an essential role in the present context and is expressed in terms of thermodynamical and of microscopical quantities, analogous to those commonly used in the superfluid nuclear model.Comment: 7 pages, RevTex, to appear in Zeit. f. Phys.