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Journal ArticleDOI
TL;DR: The typical airborne connectivity requirements and characteristics are identified, the different propagation conditions for UAVs and mobiles on the ground with measurement and ray tracing results are highlighted, and simulation results are presented to shed light on the feasibility of providing LTE connectivity for Uavs.
Abstract: Many use cases of UAVs require beyond visual LOS communications. Mobile networks offer wide-area, high-speed, and secure wireless connectivity, which can enhance control and safety of UAV operations and enable beyond visual LOS use cases. In this article, we share some of our experience in LTE connectivity for low-altitude small UAVs. We first identify the typical airborne connectivity requirements and characteristics, highlight the different propagation conditions for UAVs and mobiles on the ground with measurement and ray tracing results, and present simulation results to shed light on the feasibility of providing LTE connectivity for UAVs. We also present several ideas on potential enhancements for improving LTE connectivity performance and identify fruitful avenues for future research.

575 citations


Journal ArticleDOI
14 Apr 2020-JAMA
TL;DR: The Viewpoint updates previous guidance for clinicians and summarizes what is known, what is unknown, and what are the next steps based on available evidence to address and halt the SARS-CoV-2 outbreak.
Abstract: Since first reported in Wuhan, China, in late December 2019, the outbreak of the novel coronavirus now known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread globally. As of February 27, 2020, more than 82 000 cases of coronavirus disease 2019 (COVID-19)(thediseasecausedbySARS-CoV-2)and2800 deaths have been reported, of which approximately 95% of cases and 97% of deaths are in China.1 Cases have now been reported in 49 other countries. A particularly large outbreak occurred among the passengers and crew of the Diamond Princess cruise ship, where more than 700 infections are reported. The data surrounding the biology, epidemiology, and clinical characteristics of the SARS-CoV-2 virus have been growing daily, with more than 400 articles listed in PubMed. The virus genome was rapidly sequenced, which allowed the development of diagnostic tests and for research into vaccine and therapeutics to start. Meanwhile, the clinical spectrum of disease continues to be defined (including the potential for asymptomatic spread) and clinical trials evaluating treatments have begun. This Viewpoint updates previous guidance for clinicians2 and summarizes what is known, what is unknown, and what are the next steps based on available evidence to address and halt the outbreak.

575 citations


Journal ArticleDOI
21 Oct 2020
TL;DR: The presented work indicates that robust locomotion in natural environments can be achieved by training in simple domains.
Abstract: Legged locomotion can extend the operational domain of robots to some of the most challenging environments on Earth. However, conventional controllers for legged locomotion are based on elaborate state machines that explicitly trigger the execution of motion primitives and reflexes. These designs have increased in complexity but fallen short of the generality and robustness of animal locomotion. Here, we present a robust controller for blind quadrupedal locomotion in challenging natural environments. Our approach incorporates proprioceptive feedback in locomotion control and demonstrates zero-shot generalization from simulation to natural environments. The controller is trained by reinforcement learning in simulation. The controller is driven by a neural network policy that acts on a stream of proprioceptive signals. The controller retains its robustness under conditions that were never encountered during training: deformable terrains such as mud and snow, dynamic footholds such as rubble, and overground impediments such as thick vegetation and gushing water. The presented work indicates that robust locomotion in natural environments can be achieved by training in simple domains.

575 citations


Journal ArticleDOI
TL;DR: This work reviews the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF and offers concrete suggestions for improving EF assessment.
Abstract: Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science.

575 citations


Journal ArticleDOI
TL;DR: The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.
Abstract: The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.

575 citations


Journal ArticleDOI
03 Mar 2020-JAMA
TL;DR: An estimate of research and development costs for new therapeutic agents based on publicly available data is provided to reflect the spectrum of products analyzed, the restricted availability of data in the public domain, and differences in underlying assumptions in the cost calculations.
Abstract: Importance The mean cost of developing a new drug has been the subject of debate, with recent estimates ranging from $314 million to $2.8 billion. Objective To estimate the research and development investment required to bring a new therapeutic agent to market, using publicly available data. Design and Setting Data were analyzed on new therapeutic agents approved by the US Food and Drug Administration (FDA) between 2009 and 2018 to estimate the research and development expenditure required to bring a new medicine to market. Data were accessed from the US Securities and Exchange Commission, Drugs@FDA database, and ClinicalTrials.gov, alongside published data on clinical trial success rates. Exposures Conduct of preclinical and clinical studies of new therapeutic agents. Main Outcomes and Measures Median and mean research and development spending on new therapeutic agents approved by the FDA, capitalized at a real cost of capital rate (the required rate of return for an investor) of 10.5% per year, with bootstrapped CIs. All amounts were reported in 2018 US dollars. Results The FDA approved 355 new drugs and biologics over the study period. Research and development expenditures were available for 63 (18%) products, developed by 47 different companies. After accounting for the costs of failed trials, the median capitalized research and development investment to bring a new drug to market was estimated at $985.3 million (95% CI, $683.6 million-$1228.9 million), and the mean investment was estimated at $1335.9 million (95% CI, $1042.5 million-$1637.5 million) in the base case analysis. Median estimates by therapeutic area (for areas with ≥5 drugs) ranged from $765.9 million (95% CI, $323.0 million-$1473.5 million) for nervous system agents to $2771.6 million (95% CI, $2051.8 million-$5366.2 million) for antineoplastic and immunomodulating agents. Data were mainly accessible for smaller firms, orphan drugs, products in certain therapeutic areas, first-in-class drugs, therapeutic agents that received accelerated approval, and products approved between 2014 and 2018. Results varied in sensitivity analyses using different estimates of clinical trial success rates, preclinical expenditures, and cost of capital. Conclusions and Relevance This study provides an estimate of research and development costs for new therapeutic agents based on publicly available data. Differences from previous studies may reflect the spectrum of products analyzed, the restricted availability of data in the public domain, and differences in underlying assumptions in the cost calculations.

575 citations


Journal ArticleDOI
10 Feb 2015-JAMA
TL;DR: The objective of this study was to evaluate the accuracy of smartphone applications and wearable devices compared with direct observation of step counts, a metric successfully used in interventions to improve clinical outcomes.
Abstract: Accuracy of Smartphone Applications and Wearable Devices for Tracking Physical Activity Data Despite the potential of pedometers to increase physical activity and improve health,1 there is little evidence of broad adoption by the general population. In contrast, nearly twothirds of adults in the United States own a smartphone2 and technology advancements have enabled these devices to track health behaviors such as physical activity and provide convenient feedback.3 New wearable devices that may have more consumer appeal have also been developed. Even though these devices and applications might better engage individuals in their health, for example through workplace wellness programs,3 there has been little evaluation of their use.3-5 The objective of this study was to evaluate the accuracy of smartphone applications and wearable devices compared with direct observation of step counts, a metric successfully used in interventions to improve clinical outcomes.1

575 citations


Journal ArticleDOI
22 Oct 2015-Nature
TL;DR: It is found that sediment availability can enable mangrove forests to maintain rates of soil-surface elevation gain that match or exceed that of sea-level rise, but for 69 per cent of the study sites the current rate of sea level rise exceeded the soil surface elevation gain.
Abstract: Sea-level rise can threaten the long-term sustainability of coastal communities and valuable ecosystems such as coral reefs, salt marshes and mangroves. Mangrove forests have the capacity to keep pace with sea-level rise and to avoid inundation through vertical accretion of sediments, which allows them to maintain wetland soil elevations suitable for plant growth. The Indo-Pacific region holds most of the world's mangrove forests, but sediment delivery in this region is declining, owing to anthropogenic activities such as damming of rivers. This decline is of particular concern because the Indo-Pacific region is expected to have variable, but high, rates of future sea-level rise. Here we analyse recent trends in mangrove surface elevation changes across the Indo-Pacific region using data from a network of surface elevation table instruments. We find that sediment availability can enable mangrove forests to maintain rates of soil-surface elevation gain that match or exceed that of sea-level rise, but for 69 per cent of our study sites the current rate of sea-level rise exceeded the soil surface elevation gain. We also present a model based on our field data, which suggests that mangrove forests at sites with low tidal range and low sediment supply could be submerged as early as 2070.

575 citations


Journal ArticleDOI
Bruce Macintosh1, Bruce Macintosh2, James R. Graham3, Travis Barman4, R. J. De Rosa3, Quinn Konopacky5, Mark S. Marley6, Christian Marois7, Christian Marois8, Eric L. Nielsen2, Laurent Pueyo9, Abhijith Rajan10, Julien Rameau11, Didier Saumon12, Jason J. Wang3, Jennifer Patience10, Mark Ammons1, Pauline Arriaga13, Étienne Artigau11, Steven V. W. Beckwith3, J. Brewster, Sebastian Bruzzone14, Joanna Bulger15, Joanna Bulger10, Ben Burningham16, Ben Burningham6, Adam Burrows17, Christine Chen9, Eugene Chiang3, Jeffrey Chilcote18, Rebekah I. Dawson3, Ruobing Dong3, René Doyon11, Z. H. Draper8, Gaspard Duchêne19, Gaspard Duchêne3, Thomas M. Esposito13, Daniel C. Fabrycky20, Michael P. Fitzgerald13, Katherine B. Follette2, J. J. Fortney21, B. L. Gerard8, S. Goodsell22, A. Z. Greenbaum9, P. Hibon, Sasha Hinkley23, Tara Cotten24, Li-Wei Hung13, Patrick Ingraham, M. Johnson-Groh8, Paul Kalas3, David Lafrenière11, James E. Larkin13, J. Lee24, Michael R. Line21, Douglas Long9, Jérôme Maire18, Franck Marchis, Brenda C. Matthews7, Brenda C. Matthews8, Claire E. Max21, Stanimir Metchev25, Stanimir Metchev14, Max Millar-Blanchaer18, Tushar Mittal3, Caroline V. Morley21, Katie M. Morzinski4, R. Murray-Clay26, Rebecca Oppenheimer27, Dave Palmer1, Rahul Patel25, Marshall D. Perrin9, Lisa Poyneer1, Roman R. Rafikov17, Fredrik T. Rantakyrö, Emily L. Rice27, Patricio Rojo28, Alex Rudy21, Jean-Baptiste Ruffio2, Maria Teresa Ruiz28, Naru Sadakuni29, Leslie Saddlemyer8, M. Salama3, Dmitry Savransky30, Adam C. Schneider31, Anand Sivaramakrishnan9, Inseok Song24, Rémi Soummer9, S. Thomas, Gautam Vasisht32, James K. Wallace32, Kimberly Ward-Duong10, Sloane J. Wiktorowicz21, Schuyler Wolff9, Barry Zuckerman13 
02 Oct 2015-Science
TL;DR: Using the Gemini Planet Imager, a Jupiter-like planet is discovered orbiting the ~20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units and has a methane signature and is probably the smallest exoplanet that has been directly imaged.
Abstract: Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the Gemini Planet Imager, we discovered a planet orbiting the ~20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 × 10(-6) and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter.

575 citations


Journal ArticleDOI
23 Jun 2020-Science
TL;DR: By introducing age and activity heterogeneities into population models for SARS-CoV-2, herd immunity can be achieved at a population-wide infection rate of ∼40%, considerably lower than previous estimates.
Abstract: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates We estimate that if R0 = 25 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate

574 citations


Journal ArticleDOI
TL;DR: Results showed that the Ag nanoparticles induced visible light activity and facilitated efficient charge separation in the ZnO/Ag/CdO nanocomposite, thereby improving the photocatalytic performance.

Journal ArticleDOI
TL;DR: This work presents an approach based on disentangled representation for producing diverse outputs without paired training images, and proposes to embed images onto two spaces: a domain-invariant content space capturing shared information across domains and adomain-specific attribute space.
Abstract: Image-to-image translation aims to learn the mapping between two visual domains. There are two main challenges for many applications: (1) the lack of aligned training pairs and (2) multiple possible outputs from a single input image. In this work, we present an approach based on disentangled representation for producing diverse outputs without paired training images. To achieve diversity, we propose to embed images onto two spaces: a domain-invariant content space capturing shared information across domains and a domain-specific attribute space. Using the disentangled features as inputs greatly reduces mode collapse. To handle unpaired training data, we introduce a novel cross-cycle consistency loss. Qualitative results show that our model can generate diverse and realistic images on a wide range of tasks. We validate the effectiveness of our approach through extensive evaluation.

Journal ArticleDOI
TL;DR: Current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction are summarized, the potential of inducing cardiac regeneration through direct reprogramming of fibroblast and myofibroblasts into cardiomyocytes are discussed, and the currently available and potential future therapeutic strategies to inhibit cardiac Fibrosis are reviewed.
Abstract: Ischemic cell death during a myocardial infarction leads to a multiphase reparative response in which the damaged tissue is replaced with a fibrotic scar produced by fibroblasts and myofibroblasts. This also induces geometrical, biomechanical, and biochemical changes in the uninjured ventricular wall eliciting a reactive remodeling process that includes interstitial and perivascular fibrosis. Although the initial reparative fibrosis is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental as they lead to progressive impairment of cardiac function and eventually to heart failure. In this review, we summarize current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction, discuss the potential of inducing cardiac regeneration through direct reprogramming of fibroblasts and myofibroblasts into cardiomyocytes, and review the currently available and potential future therapeutic strategies to inhibit cardiac fibrosis. Graphical abstract Reparative response following a myocardial infarction. Hypoxia-induced cardiomyocyte death leads to the activation of myofibroblasts and a reparative fibrotic response in the injured area. Right top In adult mammals, the fibrotic scar formed at the infarcted area is permanent and promotes reactive fibrosis in the uninjured myocardium. Right bottom In teleost fish and newts and in embryonic and neonatal mammals, the initial formation of a fibrotic scar is followed by regeneration of the cardiac muscle tissue. Induction of post-infarction cardiac regeneration in adult mammals is currently the target of intensive research and drug discovery attempts.

Journal ArticleDOI
25 Aug 2015
TL;DR: Academic literacies research has developed over the past 20 years as a significant field of study that draws on a number of disciplinary fields and subfields such as applied linguistics and sociolinguistics, anthropology, sociocultural theories of learning, new literacy studies and discourse studies.
Abstract: Academic literacies research has developed over the past 20 years as a significant field of study that draws on a number of disciplinary fields and subfields such as applied linguistics and sociolinguistics, anthropology, sociocultural theories of learning, new literacy studies and discourse studies. Whilst there is fluidity and even confusion surrounding the use of the term ‘academic literacies’, we argue in this paper that it is a field of enquiry with a specific epistemological and ideological stance towards the study of academic communication and particularly, to date, writing. To define this field we situate the emergence of academic literacies research within a specific historical moment in higher education and offer an overview of the questions that the research has set out to explore. We consider debates surrounding the uses of the singular or plural forms, academic literacy/ies, and, given its position at the juncture of research/theory building and application, we acknowledge the need for strategic as well as epistemological and ideological understandings of its uses. We conclude by summarising the methodological and theoretical orientations that have developed as ‘academic literacies’, conceptualised as a field of inquiry, has expanded, and we point to areas that merit further theoretical consideration and empirical research.

Posted Content
TL;DR: It is shown that HotpotQA is challenging for the latest QA systems, and the supporting facts enable models to improve performance and make explainable predictions.
Abstract: Existing question answering (QA) datasets fail to train QA systems to perform complex reasoning and provide explanations for answers. We introduce HotpotQA, a new dataset with 113k Wikipedia-based question-answer pairs with four key features: (1) the questions require finding and reasoning over multiple supporting documents to answer; (2) the questions are diverse and not constrained to any pre-existing knowledge bases or knowledge schemas; (3) we provide sentence-level supporting facts required for reasoning, allowing QA systems to reason with strong supervision and explain the predictions; (4) we offer a new type of factoid comparison questions to test QA systems' ability to extract relevant facts and perform necessary comparison. We show that HotpotQA is challenging for the latest QA systems, and the supporting facts enable models to improve performance and make explainable predictions.

Journal ArticleDOI
TL;DR: A retrospective analysis of routine surveillance data involving children hospitalized in central Wuhan, China, for acute lower respiratory infection in early 2018 found that children with Covid-19 were more likely to be diagnosed with pneumonia than the general population.
Abstract: Children with Covid-19 in Wuhan, China A retrospective analysis of routine surveillance data involving children hospitalized in central Wuhan, China, for acute lower respiratory infection in early ...

Journal ArticleDOI
TL;DR: It is shown that the reactivation of Snai1 in mouse renal epithelial cells is required for the development of fibrosis in the kidney and that Snail1-induced fibrosis can be reversed in vivo and that obstructive nephropathy can be therapeutically ameliorated in mice by targeting Snails1 expression.
Abstract: During renal fibrosis, epithelial cells undergo a partial epithelial-to-mesenchymal transition that can be targeted to reverse established disease

Journal ArticleDOI
TL;DR: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive and the less-intensive regimen) than with cyclosporine, and a 43% reduction in the risk of death or graft loss was observed.
Abstract: BackgroundIn previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. MethodsWe randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). ResultsA total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all avail...

Journal ArticleDOI
16 Jan 2020
TL;DR: This Primer by Lord and colleagues reviews the epidemiology, mechanisms, clinical detection and treatment of autism and identifies the long-term needs of people with autism.
Abstract: Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

Journal ArticleDOI
TL;DR: Potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses in COVID-19 patients with diabetes are discussed.
Abstract: The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

Journal ArticleDOI
Liliang Ouyang1, Rui Yao1, Yu Zhao1, Wei Sun2, Wei Sun1 
TL;DR: This study provides guidance for parameter optimization and the fine-tuning of 3D cell printing processes regarding both bioink printability and cell viability after bioplotting, especially for easily damaged cells, like ESCs.
Abstract: 3D cell printing is an emerging technology for fabricating complex cell-laden constructs with precise and pre-designed geometry, structure and composition to overcome the limitations of 2D cell culture and conventional tissue engineering scaffold technology. This technology enables spatial manipulation of cells and biomaterials, also referred to as 'bioink', and thus allows study of cellular interactions in a 3D microenvironment and/or in the formation of functional tissues and organs. Recently, many efforts have been made to develop new bioinks and to apply more cell sources for better biocompatibility and biofunctionality. However, the influences of printing parameters on the shape fidelity of 3D constructs as well as on cell viability after the cell printing process have been poorly characterized. Furthermore, parameter optimization based on a specific cell type might not be suitable for other types of cells, especially cells with high sensibility. In this study, we systematically studied the influence of bioink properties and printing parameters on bioink printability and embryonic stem cell (ESC) viability in the process of extrusion-based cell printing, also known as bioplotting. A novel method was established to determine suitable conditions for bioplotting ESCs to achieve both good printability and high cell viability. The rheological properties of gelatin/alginate bioinks were evaluated to determine the gelation properties under different bioink compositions, printing temperatures and holding times. The bioink printability was characterized by a newly developed semi-quantitative method. The results demonstrated that bioinks with longer gelation times would result in poorer printability. The live/dead assay showed that ESC viability increased with higher printing temperatures and lower gelatin concentrations. Furthermore, an exponential relationship was obtained between ESC viability and induced shear stress. By defining the proper printability and acceptable viability ranges, a combined parameters region was obtained. This study provides guidance for parameter optimization and the fine-tuning of 3D cell printing processes regarding both bioink printability and cell viability after bioplotting, especially for easily damaged cells, like ESCs.


Proceedings ArticleDOI
01 Apr 2019
TL;DR: This paper gives the first attempt to explore user-level privacy leakage against the federated learning by the attack from a malicious server with a framework incorporating GAN with a multi-task discriminator, which simultaneously discriminates category, reality, and client identity of input samples.
Abstract: Federated learning, i.e., a mobile edge computing framework for deep learning, is a recent advance in privacy-preserving machine learning, where the model is trained in a decentralized manner by the clients, i.e., data curators, preventing the server from directly accessing those private data from the clients. This learning mechanism significantly challenges the attack from the server side. Although the state-of-the-art attacking techniques that incorporated the advance of Generative adversarial networks (GANs) could construct class representatives of the global data distribution among all clients, it is still challenging to distinguishably attack a specific client (i.e., user-level privacy leakage), which is a stronger privacy threat to precisely recover the private data from a specific client. This paper gives the first attempt to explore user-level privacy leakage against the federated learning by the attack from a malicious server. We propose a framework incorporating GAN with a multi-task discriminator, which simultaneously discriminates category, reality, and client identity of input samples. The novel discrimination on client identity enables the generator to recover user specified private data. Unlike existing works that tend to interfere the training process of the federated learning, the proposed method works “invisibly” on the server side. The experimental results demonstrate the effectiveness of the proposed attacking approach and the superior to the state-of-the-art.

Journal ArticleDOI
TL;DR: The potential antibacterial mechanisms ofAgNPs are analyzed, and the influences of AgNPs on osteogenic-related cells, including cellular adhesion, proliferation, and differentiation, were discussed.
Abstract: Infection, as a common postoperative complication of orthopedic surgery, is the main reason leading to implant failure. Silver nanoparticles (AgNPs) are considered as a promising antibacterial agent and always used to modify orthopedic implants to prevent infection. To optimize the implants in a reasonable manner, it is critical for us to know the specific antibacterial mechanism, which is still unclear. In this review, we analyzed the potential antibacterial mechanisms of AgNPs, and the influences of AgNPs on osteogenic-related cells, including cellular adhesion, proliferation, and differentiation, were also discussed. In addition, methods to enhance biocompatibility of AgNPs as well as advanced implants modifications technologies were also summarized.

Journal ArticleDOI
TL;DR: The concept of tailoring the properties of polylactic acid (PLA) to achieve stiffness-toughness balance along with acceptable heat resistance comes into play in this paper, where the authors summarize the recent research progress.
Abstract: Evolution of the bioplastics industry has changed directions dramatically since the early 1990s. The latest generation is moving toward durable bioplastics having high biobased content. The main objective is to replace “fossil carbon” with “renewable carbon”, a holistic strategy to mitigate climate change by minimizing the environmental impact of a product throughout its life cycle. Durable bioplastics is desired for multiuse long-term application in automotive, electronics and other industries. One necessary requirement for them is to be both tough and strong, yet the two attributes are often mutually exclusive. Does this mean a biobased and biodegradable polymer as polylactic acid (PLA) with its high strength but low toughness cannot be adopted for durable applications? Well, not exactly; this is where the concept of tailoring the properties of PLA to achieve stiffness–toughness balance along with acceptable heat resistance comes into play. In this perspective, we summarize the recent research progress ...

Proceedings Article
29 Jun 2019
TL;DR: First, convolutional self-attention is proposed by producing queries and keys with causal convolution so that local context can be better incorporated into attention mechanism, and LogSparse Transformer is proposed, improving forecasting accuracy for time series with fine granularity and strong long-term dependencies under constrained memory budget.
Abstract: Time series forecasting is an important problem across many domains, including predictions of solar plant energy output, electricity consumption, and traffic jam situation. In this paper, we propose to tackle such forecasting problem with Transformer. Although impressed by its performance in our preliminary study, we found its two major weaknesses: (1) locality-agnostics: the point-wise dot- product self-attention in canonical Transformer architecture is insensitive to local context, which can make the model prone to anomalies in time series; (2) memory bottleneck: space complexity of canonical Transformer grows quadratically with sequence length L, making directly modeling long time series infeasible. In order to solve these two issues, we first propose convolutional self-attention by producing queries and keys with causal convolution so that local context can be better incorporated into attention mechanism. Then, we propose LogSparse Transformer with only O(L(log L)^2) memory cost, improving forecasting accuracy for time series with fine granularity and strong long-term dependencies under constrained memory budget. Our experiments on both synthetic data and real- world datasets show that it compares favorably to the state-of-the-art.

Journal ArticleDOI
TL;DR: THRIVE combines the benefits of ‘classical’ apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow‐dependent deadspace flushing and has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations.
Abstract: Emergency and difficult tracheal intubations are hazardous undertakings where successive laryngoscopy–hypoxaemia–re-oxygenation cycles can escalate to airway loss and the ‘can't intubate, can't ventilate’ scenario. Between 2013 and 2014, we extended the apnoea times of 25 patients with difficult airways who were undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery. This was achieved through continuous delivery of transnasal high-flow humidified oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation during intravenous induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Apnoea time commenced at administration of neuromuscular blockade and ended with commencement of jet ventilation, positive-pressure ventilation or recommencement of spontaneous ventilation. During this time, upper airway patency was maintained with jaw-thrust. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10 females. Mean (SD [range]) age at treatment was 49 (15 [25–81]) years. The median (IQR [range]) Mallampati grade was 3 (2–3 [2–4]) and direct laryngoscopy grade was 3 (3–3 [2–4]). There were 12 obese patients and nine patients were stridulous. The median (IQR [range]) apnoea time was 14 (9–19 [5–65]) min. No patient experienced arterial desaturation < 90%. Mean (SD [range]) post-apnoea end-tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9–15.3]) kPa. The rate of increase in end-tidal carbon dioxide was 0.15 kPa.min−1. We conclude that THRIVE combines the benefits of ‘classical’ apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow-dependent deadspace flushing. It has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations from a pressured stop–start process to a smooth and unhurried undertaking.

Journal ArticleDOI
TL;DR: Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal‐flow pump was associated with better outcomes at 6 months than was implanted of an axial‐ flow pump, primarily because of the lower rate of reoperation for pump malfunction.
Abstract: BackgroundContinuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. MethodsWe randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end poi...

Journal ArticleDOI
29 Apr 2016-Science
TL;DR: The cost that an antibiotic exerts on an individual’s own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: the authors' microbiota is illustrated.
Abstract: Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.

Journal ArticleDOI
16 Oct 2015-Science
TL;DR: The ON-switch CAR exemplifies a simple and effective strategy to integrate cell-autonomous decision-making with exogenous, reversible user control and highlights the importance of developing optimized bio-inert, orthogonal control agents such as small molecules and light, together with their cellular cognate response components, in order to advance precision-controlled cellular therapeutics.
Abstract: There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control.