Statistics of correlated percolation in a bacterial community

Signal propagation over long distances is a ubiquitous feature of multicellular communities, but cell-to-cell variability can cause propagation to be highly heterogeneous. Simple models of signal propagation in heterogenous media, such as percolation theory, can potentially provide a quantitative understanding of these processes, but it is unclear whether these simple models properly capture the complexities of multicellular systems. We recently discovered that in biofilms of the bacterium Bacillus subtilis, the propagation of an electrical signal is statistically consistent with percolation theory, and yet it is reasonable to suspect that key features of this system go beyond the simple assumptions of basic percolation theory. Indeed, we find here that the probability for a cell to signal is not independent from other cells as assumed in percolation theory, but instead is correlated with its nearby neighbors. We develop a mechanistic model, in which correlated signaling emerges from cell division, phenotypic inheritance, and cell displacement, that reproduces the experimentally observed correlations. We find that the correlations do not significantly affect the spatial statistics, which we rationalize using a renormalization argument. Moreover, the fraction of signaling cells is not constant in space, as assumed in percolation theory, but instead varies within and across biofilms. We find that this feature lowers the fraction of signaling cells at which one observes the characteristic power-law statistics of cluster sizes, consistent with our experimental results. We validate the model using a mutant biofilm whose signaling probability decays along the propagation direction. Our results reveal key statistical features of a correlated signaling process in a multicellular community. More broadly, our results identify extensions to percolation theory that do or do not alter its predictions and may be more appropriate for biological systems.P50 GM085764 - NIGMS NIH HHS; Howard Hughes Medical Institute; R01 GM121888 - NIGMS NIH HHSPublished versio

Development of Aluminum LEKIDs for Balloon-Borne Far-IR Spectroscopy

We are developing lumped-element kinetic inductance detectors (LEKIDs) designed to achieve background-limited sensitivity for far-infrared (FIR) spectroscopy on a stratospheric balloon. The Spectroscopic Terahertz Airborne Receiver for Far-InfraRed Exploration (STARFIRE) will study the evolution of dusty galaxies with observations of the [CII] 158 $\mu$m and other atomic fine-structure transitions at $z=0.5-1.5$, both through direct observations of individual luminous infrared galaxies, and in blind surveys using the technique of line intensity mapping. The spectrometer will require large format ($\sim$1800 detectors) arrays of dual-polarization sensitive detectors with NEPs of $1 \times 10^{-17}$ W Hz$^{-1/2}$. The low-volume LEKIDs are fabricated with a single layer of aluminum (20 nm thick) deposited on a crystalline silicon wafer, with resonance frequencies of $100-250$ MHz. The inductor is a single meander with a linewidth of 0.4 $\mu$m, patterned in a grid to absorb optical power in both polarizations. The meander is coupled to a circular waveguide, fed by a conical feedhorn. Initial testing of a small array prototype has demonstrated good yield, and a median NEP of $4 \times 10^{-18}$ W Hz$^{-1/2}$.Comment: accepted for publication in Journal of Low Temperature Physic

Use of MMG signals for the control of powered orthotic devices: Development of a rectus femoris measurement protocol

Copyright © 2009 Rehabilitation Engineering and Assistive Technology Society (RESNA). This is an Author's Accepted Manuscript of an article published in Assistive Technology, 21(1), 1 - 12, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/10400430902945678.A test protocol is defined for the purpose of measuring rectus femoris mechanomyographic (MMG) signals. The protocol is specified in terms of the following: measurement equipment, signal processing requirements, human postural requirements, test rig, sensor placement, sensor dermal fixation, and test procedure. Preliminary tests of the statistical nature of rectus femoris MMG signals were performed, and Gaussianity was evaluated by means of a two-sided Kolmogorov-Smirnov test. For all 100 MMG data sets obtained from the testing of two volunteers, the null hypothesis of Gaussianity was rejected at the 1%, 5%, and 10% significance levels. Most skewness values were found to be greater than 0.0, while all kurtosis values were found to be greater than 3.0. A statistical convergence analysis also performed on the same 100 MMG data sets suggested that 25 MMG acquisitions should prove sufficient to statistically characterize rectus femoris MMG. This conclusion is supported by the qualitative characteristics of the mean rectus femoris MMG power spectral densities obtained using 25 averages

Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT

Background: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment, but without an adequate evidence base. / Objective: We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. / Design: Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. / Setting: Thirty-three UK maternity units. / Participants: Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20+0 and 40+6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. / Interventions: Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. / Main outcome measures: The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (< 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. / Results: Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group; adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. / Limitations: Limitations include a primary outcome event rate in the control group that was lower than that estimated for the sample size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. / Conclusions: In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. / Future work: Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. / Trial registration: Current Controlled Trials ISRCTN91918806. / Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 9. See the NIHR Journals Library website for further project information

The design and characterization of a 300 channel, optimized full-band millimeter filterbank for science with SuperSpec

SuperSpec is an integrated, on-chip spectrometer for millimeter and sub-millimeter astronomy. We report the approach, design optimization, and partial characterization of a 300 channel filterbank covering the 185 to 315 GHz frequency band that targets a resolving power R ~ 310, and fits on a 3.5×5.5 cm chip. SuperSpec uses a lens and broadband antenna to couple radiation into a niobium microstrip that feeds a bank of niobium microstrip half-wave resonators for frequency selectivity. Each half-wave resonator is coupled to the inductor of a titanium nitride lumped-element kinetic inductance detector (LEKID) that detects the incident radiation. The device was designed for use in a demonstration instrument at the Large Millimeter Telescope (LMT)

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed

Mainstreaming biodiversity : conservation for the twenty-first century

CITATION: Redford, K. H. et al. 2015. Mainstreaming biodiversity : conservation for the twenty-first century. Frontiers in Ecology and Evolution, 3:137, doi:10.3389/fevo.2015.00137.The original publication is available at http://journal.frontiersin.org/journal/ecology-and-evolutionInsufficient focused attention has been paid by the conservation community to conservation of biodiversity outside of protected areas. Biodiversity mainstreaming addresses this gap in global conservation practice by “embedding biodiversity considerations into policies, strategies and practices of key public and private actors that impact or rely on biodiversity, so that it is conserved, and sustainably used, both locally and globally” (Huntley and Redford, 2014). Biodiversity mainstreaming is designed to change those policies and practices that influence land uses outside of protected areas as well as to change economic and development decision-making by demonstrating the importance of conserving biodiversity for achieving development outcomes. The practice of mainstreaming is tied to implementation of the Convention on Biological Diversity and is practiced with billions of dollars of investment by development agencies, national government agencies, and the Global Environment Facility (GEF) and its implementing organizations as well as other donors. It is essential for the long-term survival of biodiversity inside and outside protected areas. However, it is virtually unheard of in the main conservation science field. This must change so as to bring careful documentation, analysis, monitoring, publishing, and improvement of practices—all things that conservation science should provide as partners to practitioners of biodiversity mainstreaming. The situation is ripe for informed coordination and consolidation and creation of a science-driven field of biodiversity mainstreaming.http://journal.frontiersin.org/article/10.3389/fevo.2015.00137/fullPublisher's versio

Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection