Single-cell RNA-sequencing (scRNA) datasets are becoming increasingly popular in clinical and cohort studies, but there is a lack of methods to investigate differentially expressed (DE) genes among ...such datasets with numerous individuals. While numerous methods exist to find DE genes for scRNA data from limited individuals, differential-expression testing for large cohorts of case and control individuals using scRNA data poses unique challenges due to substantial effects of human variation, i.e., individual-level confounding covariates that are difficult to account for in the presence of sparsely-observed genes.
We develop the eSVD-DE, a matrix factorization that pools information across genes and removes confounding covariate effects, followed by a novel two-sample test in mean expression between case and control individuals. In general, differential testing after dimension reduction yields an inflation of Type-1 errors. However, we overcome this by testing for differences between the case and control individuals' posterior mean distributions via a hierarchical model. In previously published datasets of various biological systems, eSVD-DE has more accuracy and power compared to other DE methods typically repurposed for analyzing cohort-wide differential expression.
eSVD-DE proposes a novel and powerful way to test for DE genes among cohorts after performing a dimension reduction. Accurate identification of differential expression on the individual level, instead of the cell level, is important for linking scRNA-seq studies to our understanding of the human population.
Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; ...therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies.
From November 2012 to April 2013, a total of 7372 healthy women aged 18–45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay.
The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0–15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18–26 years) and middle-aged women (27–45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18).
This study revealed that the majority of Chinese women aged 18–26 years and 27–45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.
•A hybrid probability uncertainty set is constructed with the density information.•A probability-driven robust transmission expansion planning model is proposed.•A slack linearization method is ...deployed to eliminate absolute value terms in H.•The large-scale model is solved by a novel column-and-constraint generation method.•Case studies on the real-world power system in northwestern China are conducted.
The incorporation of power generation derived from renewable energy sources, or renewable power generation (RPG), into conventional electric power grids has been rapidly increasing on a large scale in recent years. However, this process can be expected to inevitably increase the uncertainty associated with transmission line investment owing to the inherent uncertainty associated with RPG. While robust transmission expansion planning (RTEP) has been commonly employed for optimizing transmission line investments, this method suffers from serious disadvantages such as the neglect of available RPG probability information, overly conservative solutions, and exceedingly time consuming solution processes. The present work addresses these disadvantages by modeling the probability of RPG uncertainty according to RPG output probabilities obtained over a long-term planning horizon based on available historical data using a hybrid probability uncertainty set constructed using 1-norm and ∞-norm metrics. A probability-driven RTEP model is then proposed to obtain an optimal investment strategy that provides a security guarantee under the worst-case RPG probability distribution, while alleviating the need for overly conservative solutions with high total expansion costs. In addition, a modified column-and-constraint generation algorithm is developed to solve the proposed tri-level probability-driven RTEP model, where the large-scale inner bi-level component of the optimization problem is decomposed into several small-scale linear models that can be solved in parallel. The proposed algorithm requires no dual variables in the inner problem and eliminates all highly non-convex bilinear terms like those obtained in conventional RTEP solution algorithms. This can effectively increase the computational speed of the solution process. The effectiveness, good applicability, and robustness of the proposed model and solution algorithm are demonstrated by numerical applications based on a Garver’s 6-bus test system and an existing electric grid system in northwestern China.
Fluorescent proteins (FPs) are widely used as optical sensors, whereas other light-absorbing domains have been used for optical control of protein localization or activity. Here, we describe ...light-dependent dissociation and association in a mutant of the photochromic FP Dronpa, and we used it to control protein activities with light. We created a fluorescent light-inducible protein design in which Dronpa domains are fused to both termini of an enzyme domain. In the dark, the Dronpa domains associate and cage the protein, but light induces Dronpa dissociation and activates the protein. This method enabled optical control over guanine nucleotide exchange factor and protease domains without extensive screening. Our findings extend the applications of FPs from exclusively sensing functions to also encompass optogenetic control.
To summarise evidence about the effectiveness of home blood pressure telemonitoring (HBPT) and identify the key components of intervention. We comprehensively searched PubMed, EMBASE and the Cochrane ...Library for relevant studies. The authors were contacted for additional information. Two authors independently extracted the data and assessed the risk of bias. 46 randomised controlled trials including a total of 13 875 cases were identified. Compared with usual care, HBPT improved office systolic blood pressure (BP) and diastolic BP by 3.99 mm Hg (95% confidence interval (CI): 5.06-2.93; P<0.001) and 1.99 mm Hg (95% CI: -2.60 to -1.39; P<0.001), respectively. A larger proportion of patients achieved BP normalisation in the intervention group (relative risk (RR): 1.16; 95% CI: 1.08-1.25; P<0.001). For HBPT plus additional support (including counselling, education, behavioural management, medication management with decision, adherence contracts and so on) versus HBPT alone (or plus less intense additional support), the mean changes in systolic and diastolic BP were 2.44 mm Hg (95% Cl, 4.88 to 0.00 mm Hg; P=0.05) and 1.12 mm Hg (95% CI, -2.34 to 0.1 mm Hg; P=0.07), respectively. For those surrogate outcomes, low-strength evidence failed to show difference. In subgroup analysis, high strength evidence supported a lower BP with HBPT that lasted for 6 or 12 months and was accompanied with counselling support from study personnel. HBPT can improve BP control in the hypertensive patients. It may be more efficacious when a proactive additional support is provided during the intervention process.
Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip ...spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.
The impact of potentially pathogenic micro-organisms (PPMs) on Chinese patients with steady-state bronchiectasis is unknown.
Peripheral blood and sputum were sampled to determine inflammatory markers ...and sputum bacterial density. Spirometry and diffusing capacity were measured. Quality of life was assessed using the St George's Respiratory Questionnaire.
Of 144 patients with steady-state bronchiectasis, Pseudomonas aeruginosa was isolated in 44 cases (30.6%). Compared with other PPMs, P. aeruginosa had a more pronounced influence on airway inflammation and spirometry, but not on systemic inflammation or quality of life. The impact of PPMs other than P. aeruginosa on clinical indices was similar. Bacterial density was not correlated with most clinical parameters. Factors associated with PPM isolation included bronchiectasis symptoms for ⩾ 10 years (OR 2.13) and ⩾ 4 bronchiectatic lobes (OR 2.82). Having ⩾ 4 exacerbations within 2 years (OR 2.18) and cystic bronchiectasis (OR 2.23) was associated with the colonisation of PPMs, i.e., isolating an identical PPM on at least two occasions within 1 year.
In patients with steady-state bronchiectasis in Guangzhou, P. aeruginosa is the most common organism causing heightened airway inflammation and poor lung function. PPM isolation or colonisation should be suspected in case of longer duration of symptoms, multilobar bronchiectasis, frequent exacerbation and cystic bronchiectasis.
Many genetically encoded biosensors use Förster resonance energy transfer (FRET) to dynamically report biomolecular activities. While pairs of cyan and yellow fluorescent proteins (FPs) are most ...commonly used as FRET partner fluorophores, respectively, green and red FPs offer distinct advantages for FRET, such as greater spectral separation, less phototoxicity, and lower autofluorescence. We previously developed the green-red FRET pair Clover and mRuby2, which improves responsiveness in intramolecular FRET reporters with different designs. Here we report the engineering of brighter and more photostable variants, mClover3 and mRuby3. mClover3 improves photostability by 60% and mRuby3 by 200% over the previous generation of fluorophores. Notably, mRuby3 is also 35% brighter than mRuby2, making it both the brightest and most photostable monomeric red FP yet characterized. Furthermore, we developed a standardized methodology for assessing FP performance in mammalian cells as stand-alone markers and as FRET partners. We found that mClover3 or mRuby3 expression in mammalian cells provides the highest fluorescence signals of all jellyfish GFP or coral RFP derivatives, respectively. Finally, using mClover3 and mRuby3, we engineered an improved version of the CaMKIIα reporter Camuiα with a larger response amplitude.
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