Use of multiple singular value decompositions to analyze complex intracellular calcium ion signals

We compare calcium ion signaling ($\mathrm {Ca}^{2+}$) between two exposures; the data are present as movies, or, more prosaically, time series of images. This paper describes novel uses of singular value decompositions (SVD) and weighted versions of them (WSVD) to extract the signals from such movies, in a way that is semi-automatic and tuned closely to the actual data and their many complexities. These complexities include the following. First, the images themselves are of no interest: all interest focuses on the behavior of individual cells across time, and thus, the cells need to be segmented in an automated manner. Second, the cells themselves have 100$+$ pixels, so that they form 100$+$ curves measured over time, so that data compression is required to extract the features of these curves. Third, some of the pixels in some of the cells are subject to image saturation due to bit depth limits, and this saturation needs to be accounted for if one is to normalize the images in a reasonably unbiased manner. Finally, the $\mathrm {Ca}^{2+}$ signals have oscillations or waves that vary with time and these signals need to be extracted. Thus, our aim is to show how to use multiple weighted and standard singular value decompositions to detect, extract and clarify the $\mathrm {Ca}^{2+}$ signals. Our signal extraction methods then lead to simple although finely focused statistical methods to compare $\mathrm {Ca}^{2+}$ signals across experimental conditions.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS253 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The Challenges of Developing an Instrument to Assess Health Provider Motivation at Primary Care Level in Rural Burkina Faso, Ghana and Tanzania.

The quality of health care depends on the competence and motivation of the health workers that provide it. In the West, several tools exist to measure worker motivation, and some have been applied to the health sector. However, none have been validated for use in sub-Saharan Africa. The complexity of such tools has also led to concerns about their application at primary care level. To develop a common instrument to monitor any changes in maternal and neonatal health (MNH) care provider motivation resulting from the introduction of pilot interventions in rural, primary level facilities in Ghana, Burkina Faso, and Tanzania. Initially, a conceptual framework was developed. Based upon this, a literature review and preliminary qualitative research, an English-language instrument was developed and validated in an iterative process with experts from the three countries involved. The instrument was then piloted in Ghana. Reliability testing and exploratory factor analysis were used to produce a final, parsimonious version. This paper describes the actual process of developing the instrument. Consequently, the concepts and items that did not perform well psychometrically at pre-test are first presented and discussed. The final version of the instrument, which comprises 42 items for self-assessment and eight for peer-assessment, is then shown. This is followed by a presentation and discussion of the findings from first use of the instrument with MNH providers from 12 rural, primary level facilities in each of the three countries. It is possible to undertake work of this nature at primary health care level, particularly if the instruments are kept as straightforward as possible and well introduced. However, their development requires very lengthy preparatory periods. The effort needed to adapt such instruments for use in different countries within the region of sub-Saharan Africa should not be underestimated

Phenotypic profiles of cultured glomerular cells following repeated cycles of hydrocarbon injury

Phenotypic profiles of cultured glomerular cells following repeated cycles of hydrocarbon injury.BackgroundThe glomerulus has been implicated as a target of hydrocarbon injury in vitro and in vivo. In the present studies, the phenotypic profiles of cultured rat glomerular cells (GCs) following repeated cycles of hydrocarbon injury were evaluated. Cultured GCs were incubated for 24 hours with benzo[a]pyrene (BaP; 3 μmol/L), a prototypical polycyclic aromatic hydrocarbon, and were allowed to recover overnight before two additional cycles of chemical challenge during serial propagation in vitro. At the end of this regimen, control cultures were characterized by predominance of fusiform cells that grew in “hills and valleys,” while GCs subjected to hydrocarbon injury displayed an epithelial morphology characterized by a rounded, polygonal shape clearly distinct from that normally exhibited by glomerular mesangial cells (GMCs) in culture.MethodsIndirect immunofluorescent detection of cell markers was conducted to identify cells of mesenchymal or epithelial origin. Measurements of DNA synthesis and cell number were performed to determine proliferative capacities of the different cell types in response to hydrocarbon challenge.ResultsImmunofluorescence studies revealed that control GC cultures contained mostly α-smooth muscle (SM) actin-positive cells, with a few (5.1%± 2.6) E-cadherin–positive cells occasionally identified. In contrast, BaP-treated cultures exhibited a mixed cell population in which E-cadherin–positive cells were predominant (66.6%± 4.1). Single-cell cloning of naive cultures of GCs yielded four clones, three of which exhibited a fusiform morphology and were α-SM actin positive (SCC 1 through SCC 3) and one (SCC 4E) that exhibited epithelial characteristics similar to those found in hydrocarbon-treated cultures. Immunofluorescence studies showed that epithelial cells in hydrocarbon-treated cultures, as well as SCC 4E-derived clones, were vimentin positive and cytokeratin negative, characteristics similar to glomerular visceral epithelial cells (GVECs). DNA synthesis and cell proliferation in clone SCC 1 were decreased following acute BaP challenge, while growth rates in SCC 4E-derived clones were unaffected by hydrocarbon injury. Repeated cycles of hydrocarbon challenge in clonal populations yielded different profiles of DNA synthesis, with significant decreases in SCC 1 and no changes in SCC 4E.ConclusionsThese observations suggest that hydrocarbon injury induces differential responses in cells of the glomerulus, resulting in inhibition of GMCs and selective growth advantage of GVECs. These alterations are reminiscent of critical events described in the pathogenesis of focal segmental glomerulosclerosis and raise important questions about the pathogenesis of hydrocarbon-induced nephropathies

Gene‐specific DNA methylation may mediate atypical antipsychotic‐induced insulin resistance

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134192/1/bdi12422_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134192/2/bdi12422.pd

An EMG Gesture Recognition System with Flexible High-Density Sensors and Brain-Inspired High-Dimensional Classifier

EMG-based gesture recognition shows promise for human-machine interaction. Systems are often afflicted by signal and electrode variability which degrades performance over time. We present an end-to-end system combating this variability using a large-area, high-density sensor array and a robust classification algorithm. EMG electrodes are fabricated on a flexible substrate and interfaced to a custom wireless device for 64-channel signal acquisition and streaming. We use brain-inspired high-dimensional (HD) computing for processing EMG features in one-shot learning. The HD algorithm is tolerant to noise and electrode misplacement and can quickly learn from few gestures without gradient descent or back-propagation. We achieve an average classification accuracy of 96.64% for five gestures, with only 7% degradation when training and testing across different days. Our system maintains this accuracy when trained with only three trials of gestures; it also demonstrates comparable accuracy with the state-of-the-art when trained with one trial

Development and test results of a readout chip for the GERDA experiment

This paper describes the F-CSA104 architecture and its measurement results. The F-CSA104 is for γ spectroscopy with Ge detectors. It is a low noise, fully integrated, four channel XFAB 0.6μm CMOS technology ASIC, that has been developed for the GERDA experiment. Each channel contains a charge sensitive preamplifier (CSA) followed by a 11.7MHz differential line driver. It has been particularly designed to operate in liquid argon (T = 87K/-186°C) and to have a measuring sensitivity of 660e- with an ENC of 110e-, after offline filtering with 10μs shaping, when connected to a 30pF load. Special techniques are used to improve the SNR such as a large input PMOS FET, an integrated 500MΩ CSA feedback resistor and a noise degeneration drain resistor

Quantum dynamics of hydrogen atoms on graphene. II. Sticking

Following our recent system-bath modeling of the interaction between a hydrogen atom and a graphene surface [Bonfanti et al., J. Chem. Phys. 143, 124703 (2015)], we present the results of converged quantum scattering calculations on the activated sticking dynamics. The focus of this study is the collinear scattering on a surface at zero temperature, which is treated with high-dimensional wavepacket propagations with the multi-configuration time-dependent Hartree method. At low collision energies, barrier-crossing dominates the sticking and any projectile that overcomes the barrier gets trapped in the chemisorption well. However, at high collision energies, energy transfer to the surface is a limiting factor, and fast H atoms hardly dissipate their excess energy and stick on the surface. As a consequence, the sticking coefficient is maximum ( 3c0.65) at an energy which is about one and half larger than the barrier height. Comparison of the results with classical and quasi-classical calculations shows that quantum fluctuations of the lattice play a primary role in the dynamics. A simple impulsive model describing the collision of a classical projectile with a quantum surface is developed which reproduces the quantum results remarkably well for all but the lowest energies, thereby capturing the essential physics of the activated sticking dynamics investigated

Chemical Defense of an Asian Snake Reflects Local Availability of Toxic Prey and Hatchling Diet

Species that sequester toxins from prey for their own defense against predators may exhibit population-level variation in their chemical arsenal that reflects the availability of chemically defended prey in their habitat. Rhabdophis tigrinus is an Asian snake that possesses defensive glands in the skin of its neck (nuchal glands\u27), which typically contain toxic bufadienolide steroids that the snakes sequester from consumed toads. In this study, we compared the chemistry of the nuchal gland fluid of R.tigrinus from toad-rich and toad-free islands in Japan and determined the effect of diet on the nuchal gland constituents. Our findings demonstrate that captive-hatched juveniles from toad-rich Ishima Island that had not been fed toads possess defensive bufadienolides in their nuchal glands, presumably due to maternal provisioning of these sequestered compounds. Wild-caught juveniles from Ishima possess large quantities of bufadienolides, which could result from a combination of maternal provisioning and sequestration of these defensive compounds from consumed toads. Interestingly, juvenile females from Ishima possess larger quantities of bufadienolides than do juvenile males, whereas a small sample of field-collected snakes suggests that adult males contain larger quantities of bufadienolides than do adult females. Captive-born hatchlings from Kinkasan Island lack bufadienolides in their nuchal glands, reflecting the absence of toads on that island, but they can sequester bufadienolides by feeding on toads (Bufo japonicus) in captivity. The presence of large quantities of bufadienolides in the nuchal glands of R.tigrinus from Ishima may reduce the risk of predation by providing an effective chemical defense, whereas snakes on Kinkasan may experience increased predation due to the lack of defensive compounds in their nuchal glands