Spatial Distribution of Competing Ions around DNA in Solution

The competition of monovalent and divalent cations for proximity to negatively charged DNA is of biological importance and can provide strong constraints for theoretical treatments of polyelectrolytes. Resonant x-ray scattering experiments have allowed us to monitor the number and distribution of each cation in a mixed ion cloud around DNA. These measurements provide experimental evidence to support a general theoretical prediction: the normalized distribution of each ion around polyelectrolytes remains constant when ions are mixed at different ratios. In addition, the amplitudes of the scattering signals throughout the competition provide a measurement of the surface concentration parameter that predicts the competition behavior of these cations. The data suggest that ion size needs to be taken into account in applying Poisson-Boltzmann treatments to polyelectrolytes such as DNA

SIM-STEM Lab: Incorporating Compressed Sensing Theory for Fast STEM Simulation

Recently it has been shown that precise dose control and an increase in the overall acquisition speed of atomic resolution scanning transmission electron microscope (STEM) images can be achieved by acquiring only a small fraction of the pixels in the image experimentally and then reconstructing the full image using an inpainting algorithm. In this paper, we apply the same inpainting approach (a form of compressed sensing) to simulated, sub-sampled atomic resolution STEM images. We find that it is possible to significantly sub-sample the area that is simulated, the number of g-vectors contributing the image, and the number of frozen phonon configurations contributing to the final image while still producing an acceptable fit to a fully sampled simulation. Here we discuss the parameters that we use and how the resulting simulations can be quantifiably compared to the full simulations. As with any Compressed Sensing methodology, care must be taken to ensure that isolated events are not excluded from the process, but the observed increase in simulation speed provides significant opportunities for real time simulations, image classification and analytics to be performed as a supplement to experiments on a microscope to be developed in the future.Comment: 20 pages (includes 3 supplementary pages), 15 figures (includes 5 supplementary figures), submitted to Ultramicroscop

An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats.

We isolated an apparently new virus in the family Paramyxoviridae from stillborn piglets with deformities at a piggery in New South Wales, Australia. In 1997, the pregnancy rate and litter size at the piggery decreased markedly, while the proportion of mummified fetuses increased. We found serologic evidence of infection in pigs at the affected piggery and two associated piggeries, in humans exposed to infected pigs, and in fruit bats. Menangle virus is proposed as a common name for this agent, should further studies confirm that it is a newly recognized virus

Observed Hostility and the Risk of Incident Ischemic Heart Disease: A Prospective Population Study From the 1995 Canadian Nova Scotia Health Survey

Objectives The aim of this study was to examine the relation between hostility and incident ischemic heart disease (IHD) and to determine whether observed hostility is superior to patient-reported hostility for the prediction of IHD in a large, prospective observational study. Background Some studies have found that hostile patients have an increased risk of incident IHD. However, no studies have compared methods of hostility assessment or considered important psychosocial and cardiovascular risk factors as confounders. Furthermore, it is unknown whether all expressions of hostility carry equal risk or whether certain manifestations are more cardiotoxic. Methods We assessed the independent relationship between baseline observed hostility and 10-year incident IHD in 1,749 adults of the population-based Canadian Nova Scotia Health Survey. Results There were 149 (8.5%) incident IHD events (140 nonfatal, 9 fatal) during the 15,295 person-years of observation (9.74 events/1,000 person-years). Participants with any observed hostility had a greater risk of incident IHD than those without (p = 0.02); no such relation was found for patient-reported hostility. Those with any observed hostility had a significantly greater risk of incident IHD (hazard ratio: 2.06, 95% confidence interval: 1.04 to 4.08, p = 0.04), after adjusting for cardiovascular (age, sex, Framingham Risk Score) and psychosocial (depression, positive affect, patient-reported hostility, and anger) risk factors. Conclusions The presence of any observed hostility at baseline was associated with a 2-fold increased risk of incident IHD over 10 years of follow-up. Compared with patient-reported measures, observed hostility is a superior predictor of IHD

Simultaneous High-Speed and Low-Dose 4-D STEM Using Compressive Sensing Techniques

Here we show that compressive sensing allow 4-dimensional (4-D) STEM data to be obtained and accurately reconstructed with both high-speed and low fluence. The methodology needed to achieve these results compared to conventional 4-D approaches requires only that a random subset of probe locations is acquired from the typical regular scanning grid, which immediately generates both higher speed and the lower fluence experimentally. We also consider downsampling of the detector, showing that oversampling is inherent within convergent beam electron diffraction (CBED) patterns, and that detector downsampling does not reduce precision but allows faster experimental data acquisition. Analysis of an experimental atomic resolution yttrium silicide data-set shows that it is possible to recover over 25dB peak signal-to-noise in the recovered phase using 0.3% of the total data

A Targeted Sampling Strategy for Compressive Cryo Focused Ion Beam Scanning Electron Microscopy

Cryo Focused Ion-Beam Scanning Electron Microscopy (cryo FIB-SEM) enables three-dimensional and nanoscale imaging of biological specimens via a slice and view mechanism. The FIB-SEM experiments are, however, limited by a slow (typically, several hours) acquisition process and the high electron doses imposed on the beam sensitive specimen can cause damage. In this work, we present a compressive sensing variant of cryo FIB-SEM capable of reducing the operational electron dose and increasing speed. We propose two Targeted Sampling (TS) strategies that leverage the reconstructed image of the previous sample layer as a prior for designing the next subsampling mask. Our image recovery is based on a blind Bayesian dictionary learning approach, i.e., Beta Process Factor Analysis (BPFA). This method is experimentally viable due to our ultra-fast GPU-based implementation of BPFA. Simulations on artificial compressive FIB-SEM measurements validate the success of proposed methods: the operational electron dose can be reduced by up to 20 times. These methods have large implications for the cryo FIB-SEM community, in which the imaging of beam sensitive biological materials without beam damage is crucial.Comment: Submitted to ICASSP 202

The Potential of Subsampling and Inpainting for Fast Low-Dose Cryo FIB-SEM Imaging and Tomography

Traditional image acquisition for cryo focused ion-beam scanning electron microscopy tomography often sees thousands of images being captured over a period of many hours, with immense data sets being produced. When imaging beam sensitive materials, these images are often compromised by additional constraints related to beam damage and the devitrification of the material during imaging, which renders data acquisition both costly and unreliable. Subsampling and inpainting are proposed as solutions for both of these aspects, allowing fast and low-dose imaging to take place in the FIB-SEM without an appreciable low in image quality. In this work, experimental data is presented which validates subsampling and inpainting as a useful tool for convenient and reliable data acquisition in a FIB-SEM, with new methods of handling 3-dimensional data being employed in context of dictionary learning and inpainting algorithms using a newly developed microscope control software and data recovery algorithm.Comment: In submission to "Microscopy and Microanalysis" journal. Authorship reviewed from previous submissio

Genotoxic mixtures and dissimilar action: Concepts for prediction and assessment

This article has been made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the creative commons Attribution license which permits any use, distribution, and reproduction in any medium, provided the original author(s)and the source are credited.Combinations of genotoxic agents have frequently been assessed without clear assumptions regarding their expected (additive) mixture effects, often leading to claims of synergisms that might in fact be compatible with additivity. We have shown earlier that the combined effects of chemicals, which induce micronuclei (MN) in the cytokinesis-block micronucleus assay in Chinese hamster ovary-K1 cells by a similar mechanism, were additive according to the concept of concentration addition (CA). Here, we extended these studies and investigated for the first time whether valid additivity expectations can be formulated for MN-inducing chemicals that operate through a variety of mechanisms, including aneugens and clastogens (DNA cross-linkers, topoisomerase II inhibitors, minor groove binders). We expected that their effects should follow the additivity principles of independent action (IA). With two mixtures, one composed of various aneugens (colchicine, flubendazole, vinblastine sulphate, griseofulvin, paclitaxel), and another composed of aneugens and clastogens (flubendazole, doxorubicin, etoposide, melphalan and mitomycin C), we observed mixture effects that fell between the additivity predictions derived from CA and IA. We achieved better agreement between observation and prediction by grouping the chemicals into common assessment groups and using hybrid CA/IA prediction models. The combined effects of four dissimilarly acting compounds (flubendazole, paclitaxel, doxorubicin and melphalan) also fell within CA and IA. Two binary mixtures (flubendazole/paclitaxel and flubendazole/doxorubicin) showed effects in reasonable agreement with IA additivity. Our studies provide a systematic basis for the investigation of mixtures that affect endpoints of relevance to genotoxicity and show that their effects are largely additive.UK Food Standards Agenc