Unveiling patterns in human dominated landscapes through mapping the mass of US built structures.

Built structures increasingly dominate the Earth's landscapes; their surging mass is currently overtaking global biomass. We here assess built structures in the conterminous US by quantifying the mass of 14 stock-building materials in eight building types and nine types of mobility infrastructures. Our high-resolution maps reveal that built structures have become 2.6 times heavier than all plant biomass across the country and that most inhabited areas are mass-dominated by buildings or infrastructure. We analyze determinants of the material intensity and show that densely built settlements have substantially lower per-capita material stocks, while highest intensities are found in sparsely populated regions due to ubiquitous infrastructures. Out-migration aggravates already high intensities in rural areas as people leave while built structures remain - highlighting that quantifying the distribution of built-up mass at high resolution is an essential contribution to understanding the biophysical basis of societies, and to inform strategies to design more resource-efficient settlements and a sustainable circular economy.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.

Learning unsupervised feature representations for single cell microscopy images with paired cell inpainting.

Cellular microscopy images contain rich insights about biology. To extract this information, researchers use features, or measurements of the patterns of interest in the images. Here, we introduce a convolutional neural network (CNN) to automatically design features for fluorescence microscopy. We use a self-supervised method to learn feature representations of single cells in microscopy images without labelled training data. We train CNNs on a simple task that leverages the inherent structure of microscopy images and controls for variation in cell morphology and imaging: given one cell from an image, the CNN is asked to predict the fluorescence pattern in a second different cell from the same image. We show that our method learns high-quality features that describe protein expression patterns in single cells both yeast and human microscopy datasets. Moreover, we demonstrate that our features are useful for exploratory biological analysis, by capturing high-resolution cellular components in a proteome-wide cluster analysis of human proteins, and by quantifying multi-localized proteins and single-cell variability. We believe paired cell inpainting is a generalizable method to obtain feature representations of single cells in multichannel microscopy images.

Determinants of Mental Illness Among Humanitarian Migrants: Longitudinal Analysis of Findings From the First Three Waves of a Large Cohort Study.

Background: As refugee numbers grow worldwide, understanding prevalence and determinants of mental illness in this population becomes increasingly important. Methods: We used longitudinal data to examine the initial years of resettlement in Australian refugees with a focus on ethnic-like social support. Three annual waves from a longitudinal, nationally representative cohort of 2,399 humanitarian migrants recently resettled in Australia were examined for two mental illness outcomes: post-traumatic stress disorder indicated by positive PTSD-8 screen and "high risk of severe mental illness" (HR-SMI) by Kessler Psychological Distress Scale (K6) ≥19. Generalized linear mixed models examined demographic and resettlement factors. Findings: Contrary to predictions, high prevalence of positive screens for mental illness persisted over 3 years. At baseline, 30.3% (95% CI, 28.5-32.2) screened positive for post-traumatic stress disorder (PTSD), and 15.4% (95% CI, 14.0-16.9) had HR-SMI. Over the 3 years, 52.2% met screening criteria for mental illness. PTSD was associated with older age, females, Middle Eastern birthplace, increasing traumatic events, more financial hardships, having a chronic health condition, and poor self-rated health. HR-SMI was associated with females, Middle Eastern birthplace, unstable housing, more financial hardships, having a chronic health condition, poor self-rated health, and discrimination. Also contrary to predictions, like-ethnic social support was positively associated with PTSD (OR, 1.51; 95% CI, 1.10-2.09). Interpretation: There is high prevalence of positive screens for mental illness throughout initial years of resettlement for refugees migrating to Australia. Our unexpected finding regarding like-ethnic social support raises future avenues for research. Predictors of mental illness in the post-migration context represent tangible opportunities for intervention and are likely relevant to similar resettlement settings globally.

A comprehensive model for the proliferation-quiescence decision in response to endogenous DNA damage in human cells.

Human cells that suffer mild DNA damage can enter a reversible state of growth arrest known as quiescence. This decision to temporarily exit the cell cycle is essential to prevent the propagation of mutations, and most cancer cells harbor defects in the underlying control system. Here we present a mechanistic mathematical model to study the proliferation-quiescence decision in nontransformed human cells. We show that two bistable switches, the restriction point (RP) and the G1/S transition, mediate this decision by integrating DNA damage and mitogen signals. In particular, our data suggest that the cyclin-dependent kinase inhibitor p21 (Cip1/Waf1), which is expressed in response to DNA damage, promotes quiescence by blocking positive feedback loops that facilitate G1 progression downstream of serum stimulation. Intriguingly, cells exploit bistability in the RP to convert graded p21 and mitogen signals into an all-or-nothing cell-cycle response. The same mechanism creates a window of opportunity where G1 cells that have passed the RP can revert to quiescence if exposed to DNA damage. We present experimental evidence that cells gradually lose this ability to revert to quiescence as they progress through G1 and that the onset of rapid p21 degradation at the G1/S transition prevents this response altogether, insulating S phase from mild, endogenous DNA damage. Thus, two bistable switches conspire in the early cell cycle to provide both sensitivity and robustness to external stimuli.

Contributed Review: A review of compact interferometers.

Compact interferometers, called phasemeters, make it possible to operate over a large range while ensuring a high resolution. Such performance is required for the stabilization of large instruments dedicated to experimental physics such as gravitational wave detectors. This paper aims at presenting the working principle of the different types of phasemeters developed in the literature. These devices can be classified into two categories: homodyne and heterodyne interferometers. Improvement of resolution and accuracy has been studied for both devices. Resolution is related to the noise sources that are added to the signal. Accuracy corresponds to distortion of the phase measured with respect to the real phase, called non-linearity. The solutions proposed to improve the device resolution and accuracy are discussed based on a comparison of the reached resolutions and of the residual non-linearities.

Data-analysis strategies for image-based cell profiling.

Image-based cell profiling is a high-throughput strategy for the quantification of phenotypic differences among a variety of cell populations. It paves the way to studying biological systems on a large scale by using chemical and genetic perturbations. The general workflow for this technology involves image acquisition with high-throughput microscopy systems and subsequent image processing and analysis. Here, we introduce the steps required to create high-quality image-based (i.e., morphological) profiles from a collection of microscopy images. We recommend techniques that have proven useful in each stage of the data analysis process, on the basis of the experience of 20 laboratories worldwide that are refining their image-based cell-profiling methodologies in pursuit of biological discovery. The recommended techniques cover alternatives that may suit various biological goals, experimental designs, and laboratories' preferences.

NucliTrack: an integrated nuclei tracking application.

SUMMARY: Live imaging studies give unparalleled insight into dynamic single cell behaviours and fate decisions. However, the challenge of reliably tracking single cells over long periods of time limits both the throughput and ease with which such studies can be performed. Here, we present NucliTrack, a cross platform solution for automatically segmenting, tracking and extracting features from fluorescently labelled nuclei. NucliTrack performs similarly to other state-of-the-art cell tracking algorithms, but NucliTrack's interactive, graphical interface makes it significantly more user friendly. AVAILABILITY AND IMPLEMENTATION: NucliTrack is available as a free, cross platform application and open source Python package. Installation details and documentation are at: http://nuclitrack.readthedocs.io/en/latest/ A video guide can be viewed online: https://www.youtube.com/watch?v=J6e0D9F-qSU Source code is available through Github: https://github.com/samocooper/nuclitrack. A Matlab toolbox is also available at: https://uk.mathworks.com/matlabcentral/fileexchange/61479-samocooper-nuclitrack-matlab. CONTACT: sam@socooper.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Accelerating Live Single-Cell Signalling Studies.

The dynamics of signalling networks that couple environmental conditions with cellular behaviour can now be characterised in exquisite detail using live single-cell imaging experiments. Recent improvements in our abilities to introduce fluorescent sensors into cells, coupled with advances in pipelines for quantifying and extracting single-cell data, mean that high-throughput systematic analyses of signalling dynamics are becoming possible. In this review, we consider current technologies that are driving progress in the scale and range of such studies. Moreover, we discuss novel approaches that are allowing us to explore how pathways respond to changes in inputs and even predict the fate of a cell based upon its signalling history and state.

Visualizing quantitative microscopy data: History and challenges.

Data visualization is a fundamental aspect of science. In the context of microscopy-based studies, visualization typically involves presentation of the images themselves. However, data visualization is challenging when microscopy experiments entail imaging of millions of cells, and complex cellular phenotypes are quantified in a high-content manner. Most well-established visualization tools are inappropriate for displaying high-content data, which has driven the development of new visualization methodology. In this review, we discuss how data has been visualized in both classical and high-content microscopy studies; as well as the advantages, and disadvantages, of different visualization methods.

Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells.

Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space--an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.

Cross-talk between Rho and Rac GTPases drives deterministic exploration of cellular shape space and morphological heterogeneity.

One goal of cell biology is to understand how cells adopt different shapes in response to varying environmental and cellular conditions. Achieving a comprehensive understanding of the relationship between cell shape and environment requires a systems-level understanding of the signalling networks that respond to external cues and regulate the cytoskeleton. Classical biochemical and genetic approaches have identified thousands of individual components that contribute to cell shape, but it remains difficult to predict how cell shape is generated by the activity of these components using bottom-up approaches because of the complex nature of their interactions in space and time. Here, we describe the regulation of cellular shape by signalling systems using a top-down approach. We first exploit the shape diversity generated by systematic RNAi screening and comprehensively define the shape space a migratory cell explores. We suggest a simple Boolean model involving the activation of Rac and Rho GTPases in two compartments to explain the basis for all cell shapes in the dataset. Critically, we also generate a probabilistic graphical model to show how cells explore this space in a deterministic, rather than a stochastic, fashion. We validate the predictions made by our model using live-cell imaging. Our work explains how cross-talk between Rho and Rac can generate different cell shapes, and thus morphological heterogeneity, in genetically identical populations.

Signature profiling and classification of illicit heroin by GC-MS analysis of acidic and neutral manufacturing impurities.

The illicit manufacture of heroin results in the formation of trace level acidic and neutral impurities. These impurities are detectable in illicit heroin and provide valuable information about the manufacturing process used. The isolation, derivatization, and semiquantitative analysis of neutral and acidic heroin manufacturing impurities by programmed temperature vaporizing injector-gas chromatography-mass spectrometry (PTV-GC-MS) is described. Trace acidic and neutral heroin impurities were isolated from basic fractions using liquid-liquid extraction. Extracted impurities were treated with N-Methyl-N-trimethylsilyltrifluoroacetamide followed by PTV-GC-MS analyses. Semiquantitative data were obtained using full scan mass spectrometry utilizing unique ions or ion combinations for 36 trace impurities found in crude and/or highly refined heroin samples. Minimum detection limits for acidic and neutral impurities were estimated to be at the 10(-7) level relative to total morphine. Over 500 authentic heroin samples from South America, Mexico, Southwest Asia, and Southeast Asia were analyzed. Classification of illicit heroin based on the presence or absence and relative amounts of acidic and neutral impurities is presented.

CSHCN in Texas: meeting the need for specialist care.

OBJECTIVE: Assuring the sufficiency and suitability of systems of care and services for children with special health care needs (CSHCN) presents a challenge to Texas providers, agencies, and state Title V programs. To meet the need for specialist care, referrals from primary care doctors are often necessary. The objective of this study was to describe the factors associated with the need for specialist care and problems associated with obtaining referrals in Texas. METHODS: Bivariate and multivariate analyses were performed using the National Survey of Children with Special Health Care Needs (NS-CSHCN) weighted sample for Texas (n = 719,014) to identify variables associated with the need for specialist care and problems obtaining referrals for specialist care. RESULTS: Medical need of the CSHCN and sensitivity to family values/customs was associated with greater need for specialist care, and Hispanic ethnicity and lower maternal education were associated with less need. Medical need, amount of time spent with doctors and sensitivity to values/customs, living in a large metropolitan statistical area, and lack of medical information were associated with problems obtaining a specialist care referral. CONCLUSIONS: Findings revealed some similarities and differences with meeting the need for specialist care when comparing Texas results to other studies. In Texas, aspects of customer satisfaction variables, especially doctors' sensitivity to family values/customs and parents' not receiving enough information on medical problems, were significantly associated with problems obtaining specialist referrals. Findings indicate a need to further research relationships and communication among doctors, CSHCN, and their families.