Explicit integration of differential equations

Explicit integration of differential equation

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

Teacher autonomy: Good for pupils? Good for teachers?

Should teachers have complete autonomy over teaching methods and practices, or should some aspects of their practice be determined by school or government policy? We address this question using repeated (value-added) maths test scores linked to rich survey data from the TALIS video study. With the possible exception of inexperienced teachers, we generally find no relationship between teacher autonomy and pupil outcomes (test scores, maths self-efficacy or interest in maths). In partial contrast with our findings for pupil outcomes, teachers with very low levels of autonomy are more likely to report reduced job satisfaction. It may hence be that some level of restriction on teacher autonomy is justified, especially among inexperienced teachers, particularly when it represents only partial control of teachers’ approaches in the classroom and is done to introduce evidence-based methods

Empirical Implications of Arbitrage-Free Asset Markets

The martingale-equivalence condition delivered by a non-arbitrage assumption in complete asset markets has implications for fine-time-unit asset price behavior that can be rejected with finite spans of data. A class of stochastic processes that could model such deviations from martingale-equivalence is proposed.Asset market, asset pricing

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

A Picard Iterative Method for Estimating Solutions to Certain Differential Equations

Numerical implementation of Picard iteration for estimating solutions to certain differential equation

Mars rover sample return: An exobiology science scenario

A mission designed to collect and return samples from Mars will provide information regarding its composition, history, and evolution. At the same time, a sample return mission generates a technical challenge. Sophisticated, semi-autonomous, robotic spacecraft systems must be developed in order to carry out complex operations at the surface of a very distant planet. An interdisciplinary effort was conducted to consider how much a Mars mission can be realistically structured to maximize the planetary science return. The focus was to concentrate on a particular set of scientific objectives (exobiology), to determine the instrumentation and analyses required to search for biological signatures, and to evaluate what analyses and decision making can be effectively performed by the rover in order to minimize the overhead of constant communication between Mars and the Earth. Investigations were also begun in the area of machine vision to determine whether layered sedimentary structures can be recognized autonomously, and preliminary results are encouraging

Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide.

Resistance to chemotherapy substantially hinders successful glioblastoma (GBM) treatment, contributing to an almost 100% mortality rate. Resistance to the frontline chemotherapy, temozolomide (TMZ), arises from numerous signaling pathways that are deregulated in GBM, including Hedgehog (Hh) signaling. Here, we investigate suppression of Hh signaling as an adjuvant to TMZ using U87-MG and T98G cell lines as in vitro models of GBM. We found that silencing GLI1 with siRNA reduces cell metabolic activity by up to 30% in combination with TMZ and reduces multidrug efflux activity by 2.5-fold. Additionally, pharmacological GLI inhibition modulates nuclear p53 levels and decreases MGMT expression in combination with TMZ. While we surprisingly found that silencing GLI1 does not induce apoptosis in the absence of TMZ co-treatment, we discovered silencing GLI1 without TMZ co-treatment induces senescence as evidenced by a significant 2.3-fold increase in senescence associated β-galactosidase staining, and this occurs in a loss of PTEN-dependent manner. Finally, we show that GLI inhibition increases apoptosis in glioma stem-like cells by up to 6.8-fold in combination with TMZ, and this reduces the size and number of neurospheres grown from glioma stem-like cells. In aggregate, our data warrant the continued investigation of Hh pathway inhibitors as adjuvants to TMZ chemotherapy and highlight the importance of identifying signaling pathways that determine whether co-treatment will be successful

The role of tool geometry in process damped milling

The complex interaction between machining structural systems and the cutting process results in machining instability, so called chatter. In some milling scenarios, process damping is a useful phenomenon that can be exploited to mitigate chatter and hence improve productivity. In the present study, experiments are performed to evaluate the performance of process damped milling considering different tool geometries (edge radius, rake and relief angles and variable helix/pitch). The results clearly indicate that variable helix/pitch angles most significantly increase process damping performance. Additionally, increased cutting edge radius moderately improves process damping performance, while rake and relief angles have a smaller and closely coupled effect

MoonLITE – Technological feasibility of the penetrator concept

Introduction: While the surface missions to the Moon of the 1960s and 1970s achieved a great deal, scientifically a great deal was also left unresolved. The recent plethora of lunar missions (flown or proposed) reflects resurgence in interest in the Moon, not only in its own right, but also as a record of the formation of the Earth-Moon System and the interplanetary environment at 1 AU. Results from orbiter missions have indicated the possible presense of ice within permanently shaded craters at the lunar poles [1] – a situation that, if confirmed, will have profound impacts on lunar exploration