A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging

An ongoing challenge in biomedical research is the search for simple, yet robust assays using 3D cell cultures for toxicity screening. This study addresses that challenge with a novel spheroid assay, wherein spheroids, formed by magnetic 3D bioprinting, contract immediately as cells rearrange and compact the spheroid in relation to viability and cytoskeletal organization. Thus, spheroid size can be used as a simple metric for toxicity. The goal of this study was to validate spheroid contraction as a cytotoxic endpoint using 3T3 fibroblasts in response to 5 toxic compounds (all-trans retinoic acid, dexamethasone, doxorubicin, 5′-fluorouracil, forskolin), sodium dodecyl sulfate (+control), and penicillin-G (−control). Real-time imaging was performed with a mobile device to increase throughput and efficiency. All compounds but penicillin-G significantly slowed contraction in a dose-dependent manner (Z’ = 0.88). Cells in 3D were more resistant to toxicity than cells in 2D, whose toxicity was measured by the MTT assay. Fluorescent staining and gene expression profiling of spheroids confirmed these findings. The results of this study validate spheroid contraction within this assay as an easy, biologically relevant endpoint for high-throughput compound screening in representative 3D environments

Estimating the Reproducibility of Experimental Philosophy

Responding to recent concerns about the reliability of the published literature in psychology and other disciplines, we formed the X-Phi Replicability Project (XRP) to estimate the reproducibility of experimental philosophy (osf.io/dvkpr). Drawing on a representative sample of 40 x-phi studies published between 2003 and 2015, we enlisted 20 research teams across 8 countries to conduct a high-quality replication of each study in order to compare the results to the original published findings. We found that x-phi studies – as represented in our sample – successfully replicated about 70% of the time. We discuss possible reasons for this relatively high replication rate in the field of experimental philosophy and offer suggestions for best research practices going forward

Uncertainty-aware 3D Object-Level Mapping with Deep Shape Priors

3D object-level mapping is a fundamental problem in robotics, which is especially challenging when object CAD models are unavailable during inference. In this work, we propose a framework that can reconstruct high-quality object-level maps for unknown objects. Our approach takes multiple RGB-D images as input and outputs dense 3D shapes and 9-DoF poses (including 3 scale parameters) for detected objects. The core idea of our approach is to leverage a learnt generative model for shape categories as a prior and to formulate a probabilistic, uncertainty-aware optimization framework for 3D reconstruction. We derive a probabilistic formulation that propagates shape and pose uncertainty through two novel loss functions. Unlike current state-of-the-art approaches, we explicitly model the uncertainty of the object shapes and poses during our optimization, resulting in a high-quality object-level mapping system. Moreover, the resulting shape and pose uncertainties, which we demonstrate can accurately reflect the true errors of our object maps, can also be useful for downstream robotics tasks such as active vision. We perform extensive evaluations on indoor and outdoor real-world datasets, achieving achieves substantial improvements over state-of-the-art methods. Our code will be available at https://github.com/TRAILab/UncertainShapePose.Comment: Manuscript submitted to ICRA 202

Modeling community integration in workers with delayed recovery from mild traumatic brain injury

Background: Delayed recovery in persons after mild traumatic brain injury (mTBI) is poorly understood. Community integration (CI) is endorsed by persons with neurological disorders as an important outcome. We aimed to describe CI and its associated factors in insured Ontario workers with delayed recovery following mTBI. Methods: A cross-sectional study of insured workers in the chronic phase following mTBI was performed at a rehabilitation hospital in Ontario, Canada. Sociodemographic, occupational, injury-related, clinical, and claim-related data were collected from self-reports, medical assessments, and insurers’ referral files. Community Integration Questionnaire (CIQ) scores were compared using analysis of variance or Spearman’s correlation tests. Stepwise multivariable linear regression models were used to evaluate the associations with CI. Results: Ninety-four workers with mTBI (45.2 ± 9.9 years old, 61.2 % male) at 197 days post-injury (interquartile range, 139–416 days) were included. The CIQ total and subscale scores were similar to those reported in more severe TBI samples. The CIQ scores were moderately to strongly correlated with various sociodemographic, claim-related, and clinical variables. In the multivariable regression analysis, several covariates accounted for 36.4 % of the CIQ variance in the final fully adjusted model. Discussion: This study evaluated CI in workers with mTBI, and analyzed its associated variables. Analysis revealed insomnia, head or neck pain, being married or in a relationship, time since injury, and a diagnosis of possible/probable malingering were independently associated with limited CI. Conclusions: Workers with delayed recovery from mTBI experience difficulty with CI. Insomnia is a particularly relevant covariate, explaining the greater part of its variance. To enhance participation, care should focus on clinical and non-clinical covariates

Muon reconstruction performance of the ATLAS detector in proton–proton collision data at √s = 13 TeV

This article documents the performance of the ATLAS muon identification and reconstruction using the LHC dataset recorded at √s = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9 % while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%

Biosynthesis of long-chain polyunsaturated fatty acids in the razor clam Sinonovacula constricta: characterization of four fatty acyl elongases and a novel desaturase capacity

As an unusual economically important aquaculture species, Sinonovacula constricta possesses high levels of long-chain polyunsaturated fatty acids (LC-PUFA). Previously, our group identified fatty acyl desaturases (Fad) with Δ5 and Δ6 activities in S. constricta, which was the first report of Δ6 Fad in a marine mollusc. Here, we further successfully characterize elongases of very long-chain fatty acids (Elovl) in this important bivalve species, including one Elovl2/5, two Elovl4 isoforms (a and b) and a novel Elovl (c) with Elovl4 activity. In addition, we also determined the desaturation activity of S. constricta Δ6 Fad toward 24:5n-3 to give 24:6n-3, a key intermediate in docosahexaenoic acid (DHA) biosynthesis. Therefore, S. constricta is the first marine mollusc reported to possess all Fad and Elovl activities required for LC-PUFA biosynthesis via the ‘Sprecher pathway’. This finding greatly increases our understanding of LC-PUFA biosynthesis in marine molluscs. Phylogenetic analysis by interrogating six marine molluscan genomes, and previously functionally characterized Elovl and Fad from marine molluscs, suggested that DHA biosynthetic ability was limited to a few species, due to the general lack of Δ4 or Δ6 Fad in most molluscs

RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia

Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animal models that recapitulate bronchiolitis and bronchopneumonia, both hallmark features of severe RSV infection in humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV, resulting in sustained virus replication. Here we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV-infected epithelial cells lining the airway and the alveolar regions of human lung implants result in hallmark histological features of RSV bronchiolitis and bronchopneumonia, including distal airway and alveolar lumens clogged with (1) sloughed and necrotic RSV-infected epithelial cells, (2) neutrophil-containing inflammatory infiltrates, and (3) MUC5B-dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Our data together show that RSV infection of human lung implants in vivo exhibits appropriate cellular tropism and results in the hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection

Combinatorics of generalized parking-function polytopes

For $\mathbf{b}=(b_1,\dots,b_n)\in \mathbb{Z}_{>0}^n$, a $\mathbf{b}$-parking function is defined to be a sequence $(\beta_1,\dots,\beta_n)$ of positive integers whose nondecreasing rearrangement $\beta'_1\leq \beta'_2\leq \cdots \leq \beta'_n$ satisfies $\beta'_i\leq b_1+\cdots + b_i$. The $\mathbf{b}$-parking-function polytope $\mathfrak{X}_n(\mathbf{b})$ is the convex hull of all $\mathbf{b}$-parking functions of length $n$ in $\mathbb{R}^n$. Geometric properties of $\mathfrak{X}_n(\mathbf{b})$ were previously explored in the specific case where $\mathbf{b}=(a,b,b,\dots,b)$ and were shown to generalize those of the classical parking-function polytope. In this work, we study $\mathfrak{X}_n(\mathbf{b})$ in full generality. We present a minimal inequality and vertex description for $\mathfrak{X}_n(\mathbf{b})$, prove it is a generalized permutahedron, and study its $h$-polynomial. Furthermore, we investigate $\mathfrak{X}_n(\mathbf{b})$ through the perspectives of building sets and polymatroids, allowing us to identify its combinatorial types and obtain bounds on its combinatorial and circuit diameters.Comment: 27 pages, 4 figures, Comments welcomed

A Power-Efficient Multiband Planar USB Dongle Antenna for Wireless Sensor Networks

Wireless Sensor Networks (WSNs) had been applied in Internet of Things (IoT) and in Industry 4.0. Since a WSN system contains multiple wireless sensor nodes, it is necessary to develop a low-power and multiband wireless communication system that satisfies the specifications of the Federal Communications Commission (FCC) and the Certification European (CE). In a WSN system, many devices are of very small size and can be slipped into a Universal Serial Bus (USB), which is capable of connecting to wireless systems and networks, as well as transferring data. These devices are widely known as USB dongles. This paper develops a planar USB dongle antenna for three frequency bands, namely 2.30–2.69 GHz, 3.40–3.70 GHz, and 5.15–5.85 GHz. This study proposes a novel antenna design that uses four loops to develop the multiband USB dongle. The first and second loops construct the low and intermediate frequency ranges. The third loop resonates the high frequency property, while the fourth loop is used to enhance the bandwidth. The performance and power consumption of the proposed multiband planar USB dongle antenna were significantly improved compared to existing multiband designs