69 research outputs found

    Compact, Field-Portable Lens-free Microscope using Superresolution Spatio-Spectral Light-field Fusion

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    We present a compact, field-portable lens-free microscope basedon the principle of spatio-spectral light-field fusion. This is the firsttime a device of this kind has been introduced whereby both superresolutionand signal-to-noise ratio are enhanced via the marriageof synthetic aperture imaging and spectral light-field fusionholography, culminating in a system that is self-contained and fieldportablewhile achieving high resolution, contrast, strong signal fidelity,and ultra-wide field-of-view. The active spatio-spectral illuminationis accomplished in the presented microscope by arranginga series of pulsing LEDs emitting at different spectral wavelengthsin a specific spatial formation. To demonstrate the performance ofthe presented microscope, the system was used to observe twohistology samples: a bovine lung, and corn stem. The imaging resultsdemonstrate the ultra-wide field-of-view advantage of the presentedmicroscope over any other system of its kind, thus enablingfor acquisition of the entire sample without the need for scanning,while producing high-resolution, high-contrast microscopy images(168 megapixels in the current system) that makes it well-suited forscientific and clinical examinations

    Enhanced Smartphone Spectroscopy via High-throughput Computational Slit

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    High-performance spectroscopy is often limited by its portability, size, and cost, therefore limiting its reach into various applications that may benefit from it. In this paper, we present a low-cost, low-complexity slitless smartphone-based spectrometer that can be useful for carrying out field studies. Omitting a slit in a spectrometer means loss of spectral resolution in conventional spectrographs; however, we overcome this limitation via the use of a high-throughput computational slit to produce spectra with enhanced spectral resolution and enhanced signal-to-noise characteristics

    Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces

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    Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary events leading to the diversification of this genus over the last 20 million years. Here, we show the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.Some computations were performed on Tirant III of the Spanish Supercomputing Network (“Servei d’Informàtica de la Universitat de València”) under the project BCV-2021-1-0001 granted to DP, while others were performed at the Wisconsin Energy Institute and the Center for High-Throughput Computing of the University of Wisconsin–Madison. During a portion of this project, DP was a researcher funded by the European Union’s Horizon 2020 research and innovation program Marie Sklodowska-Curie, grant agreement No. 747775, the Research Council of Norway (RCN) grant Nos. RCN 324253 and 274337, and the Generalitat Valenciana plan GenT grant No. CIDEGENT/2021/039. D.P. is a recipient of an Illumina Grant for Illumina Sequencing Saccharomyces strains in this study. Q.K.L. was supported by the National Science Foundation under Grant No. DGE-1256259 (Graduate Research Fellowship) and the Predoctoral Training Program in Genetics, funded by the National Institutes of Health (5T32GM007133). This material is based upon work supported in part by the Great Lakes Bioenergy Research Center, Office of Science, Office of Biological and Environmental Research under Award Numbers DE-SC0018409 and DE-FC02-07ER64494; the National Science Foundation under Grant Nos. DEB-1253634, DEB−1442148, and DEB-2110403; and the USDA National Institute of Food and Agriculture Hatch Project Number 1020204. C.T.H. is an H. I. Romnes Faculty Fellow, supported by the Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation. QMW was supported by the National Natural Science Foundation of China (NSFC) under Grant Nos. 31770018 and 31961133020. C.R.L. holds the Canada Research Chair in Cellular Systems and Synthetic Biology, and his research on wild yeast is supported by an NSERC Discovery Grant.Peer reviewe

    Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

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    Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

    Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

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    A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

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    Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

    Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

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    publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

    Determining and Controlling the Stoichiometry of Cu<sub>2</sub>ZnSnS<sub>4</sub> Photovoltaics: The Physics and Its Implications

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    Cu<sub>2</sub>ZnSnS<sub>4</sub> (CZTS) is an environmentally friendly photovoltaic material with promising applications in thin-film solar cells. Although CZTS’s efficiency is currently too low, stoichiometry/defect engineering presents a strategy for further improvement. As-grown CZTS is typically disordered and therefore prone to form secondary phases, making the final product stoichiometry difficult to determine and even harder to control. We use first-principles quantum mechanics in combination with Monte Carlo simulations to determine CZTS stoichiometry under various experimental conditions. We develop an approach to predicting the optimal CZTS stoichiometry, explaining the physical origin of Zn-enrichment observed in experiments. We further propose practical ways to introduce more free carriers into CZTS in order to screen observed local potential fluctuations, increase conductivity, and ultimately improve the efficiency of CZTS
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