Tracking autophagy during proliferation and differentiation of trypanosoma brucei

Autophagy is a lysosome-dependent degradation mechanism that sequesters target cargo into autophagosomal vesicles. The Trypanosoma brucei genome contains apparent orthologues of several autophagy-related proteins including an ATG8 family. These ubiquitin-like proteins are required for autophagosome membrane formation, but our studies show that ATG8.3 is atypical. To investigate the function of other ATG proteins, RNAi compatible T. brucei were modified to function as autophagy reporter lines by expressing only either YFP-ATG8.1 or YFP-ATG8.2. In the insect procyclic lifecycle stage, independent RNAi down-regulation of ATG3 or ATG7 generated autophagy-defective mutants and confirmed a pro-survival role for autophagy in the procyclic form nutrient starvation response. Similarly, RNAi depletion of ATG5 or ATG7 in the bloodstream form disrupted autophagy, but did not impede proliferation. Further characterisation showed bloodstream form autophagy mutants retain the capacity to undergo the complex cellular remodelling that occurs during differentiation to the procyclic form and are equally susceptible to dihydroxyacetone-induced cell death as wild type parasites, not supporting a role for autophagy in this cell death mechanism. The RNAi reporter system developed, which also identified TOR1 as a negative regulator controlling YFP-ATG8.2 but not YFP-ATG8.1 autophagosome formation, will enable further targeted analysis of the mechanisms and function of autophagy in the medically relevant bloodstream form of T. brucei

Segmented waveguides in thin silicon-on-insulator

We have developed new silicon-on-insulator waveguide designs for simultaneously achieving both low-loss optical confinement and electrical contacts, and we present a design methodology based on calculating the Bloch modes of such segmented waveguides. With this formalism, waveguides are designed in a single thin layer of silicon-on-insulator to achieve both optical confinement and minimal insertion loss. Waveguides were also fabricated and tested, and the measured data were found to closely agree with theoretical predictions, demonstrating input insertion loss and propagation loss better than 0.1 dB and -16 dB/cm, respectively

Control theory for principled heap sizing

We propose a new, principled approach to adaptive heap sizing based on control theory. We review current state-of-the-art heap sizing mechanisms, as deployed in Jikes RVM and HotSpot. We then formulate heap sizing as a control problem, apply and tune a standard controller algorithm, and evaluate its performance on a set of well-known benchmarks. We find our controller adapts the heap size more responsively than existing mechanisms. This responsiveness allows tighter virtual machine memory footprints while preserving target application throughput, which is ideal for both embedded and utility computing domains. In short, we argue that formal, systematic approaches to memory management should be replacing ad-hoc heuristics as the discipline matures. Control-theoretic heap sizing is one such systematic approach

Transition to organic farming negatively affects bat activity

1. The effectiveness of organic farming on biodiversity has been widely documented especially for plants, arthropods and birds; however, the effects of the transition period required to become an organic farm on wildlife remain poorly understood.2. We assessed the effects of organic farming on insectivorous bats in citrus orchards in the Republic of Cyprus employing two matched designs (conventional vs. 3-year organic-transitional and conventional vs. organic-certified) and a third unmatched design (3-year organic-transitional vs. organic-certified). We specifically investigated whether the transition period prior to full organic certification influenced bat activity with a special focus on any moderation effects from surrounding semi-natural areas.3. The activity of three (Pipistrellus kuhlii, Hypsugo savii and Miniopterus schreibersii) of four bat species was significantly lower in farms undergoing the transitional period than in conventional farms, and P. kuhlii and H. savii were significantly less active in organic transitional farming systems that in organic-certified ones. Furthermore, the activity of the most dominant species (P. kuhlii) was significantly higher on organic than transitional and conventional citrus orchards, thus suggesting a time-lag effect. Landscape complexity measured as the amount of semi-natural areas did not moderate the effects of farming system for any study species.4. Synthesis and application. The transition to organic farming had persistent detrimental effects on bats and potentially on the pest suppression services they provide. Future agri-environmental policy should consider the transition period and implement measures to mitigate any negative effects on biodiversity, alongside promoting asynchronous transition of nearby farms. Our findings further highlight the crucial need to consider the time since transition to organic farming when assessing potential benefits of organic management on biodiversity

Toward a Symphony of Reactivity: Cascades Involving Catalysis and Sigmatropic Rearrangements

Catalysis and synthesis are intimately linked in modern organic chemistry. The synthesis of complex molecules is an ever evolving area of science. In many regards, the inherent beauty associated with a synthetic sequence can be linked to a certain combination of the creativity with which a sequence is designed and the overall efficiency with which the ultimate process is performed. In synthesis, as in other endeavors, beauty is very much in the eyes of the beholder.† It is with this in mind that we will attempt to review an area of synthesis that has fascinated us and that we find extraordinarily beautiful, namely the combination of catalysis and sigmatropic rearrangements in consecutive and cascade sequences

High eccentricity planets from the Anglo-Australian Planet Search

We report Doppler measurements of the stars HD187085 and HD20782 which indicate two high eccentricity low-mass companions to the stars. We find HD187085 has a Jupiter-mass companion with a ~1000d orbit. Our formal `best fit' solution suggests an eccentricity of 0.47, however, it does not sample the periastron passage of the companion and we find that orbital solutions with eccentricities between 0.1 and 0.8 give only slightly poorer fits (based on RMS and chi^2) and are thus plausible. Observations made during periastron passage in 2007 June should allow for the reliable determination of the orbital eccentricity for the companion to HD187085. Our dataset for HD20782 does sample periastron and so the orbit for its companion can be more reliably determined. We find the companion to HD20782 has M sin i=1.77+/-0.22M_JUP, an orbital period of 595.86+/-0.03d and an orbit with an eccentricity of 0.92+/-0.03. The detection of such high-eccentricity (and relatively low velocity amplitude) exoplanets appears to be facilitated by the long-term precision of the Anglo-Australian Planet Search. Looking at exoplanet detections as a whole, we find that those with higher eccentricity seem to have relatively higher velocity amplitudes indicating higher mass planets and/or an observational bias against the detection of high eccentricity systems.Comment: to appear in MNRA

Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

BACKGROUND: Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. RESULTS: We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. CONCLUSIONS: This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets, including high resolution confocal images, live cell time-lapse recordings, and high-throughput screening data sets

Layer-Parallel Training with GPU Concurrency of Deep Residual Neural Networks via Nonlinear Multigrid

A Multigrid Full Approximation Storage algorithm for solving Deep Residual Networks is developed to enable neural network parallelized layer-wise training and concurrent computational kernel execution on GPUs. This work demonstrates a 10.2x speedup over traditional layer-wise model parallelism techniques using the same number of compute units.Comment: 7 pages, 6 figures, 27 citations. Accepted to 2020 IEEE High Performance Extreme Computing Conference - Outstanding Paper Awar