7,359 research outputs found

    A direct-laser-written heart-on-a-chip platform for generation and stimulation of engineered heart tissues

    Full text link
    In this dissertation, we first develop a versatile microfluidic heart-on-a-chip model to generate 3D-engineered human cardiac microtissues in highly-controlled microenvironments. The platform, which is enabled by direct laser writing (DLW), has tailor-made attachment sites for cardiac microtissues and comes with integrated strain actuators and force sensors. Application of external pressure waves to the platform results in controllable time-dependent forces on the microtissues. Conversely, oscillatory forces generated by the microtissues are transduced into measurable electrical outputs. After characterization of the responsivity of the transducers, we demonstrate the capabilities of this platform by studying the response of cardiac microtissues to prescribed mechanical loading and pacing. Next, we tune the geometry and mechanical properties of the platform to enable parametric studies on engineered heart tissues. We explore two geometries: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites. The attachment sites are placed symmetrically in the longitudinal direction. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length for both configurations and observe a positive correlation between fiber alignment at the center of the microtissues and tissue length. However, progressive thinning and “necking” is also observed, leading to the failure of longer tissues over time. We use the DLW technique to improve the platform, softening the mechanical environment and optimizing the attachment sites for generation of stable microtissues at each length and geometry. Furthermore, electrical pacing is incorporated into the platform to evaluate the functional dynamics of stable microtissues over the entire range of physiological heart rates. Here, we typically observe a decrease in active force and contraction duration as a function of frequency. Lastly, we use a more traditional ?TUG platform to demonstrate the effects of subthreshold electrical pacing on the rhythm of the spontaneously contracting cardiac microtissues. Here, we observe periodic M:N patterns, in which there are ? cycles of stimulation for every ? tissue contractions. Using electric field amplitude, pacing frequency, and homeostatic beating frequencies of the tissues, we provide an empirical map for predicting the emergence of these rhythms

    REDESIGNING THE COUNTER UNMANNED SYSTEMS ARCHITECTURE

    Get PDF
    Includes supplementary material. Please contact [email protected] for access.When the Islamic State used Unmanned Aerial Vehicles (UAV) to target coalition forces in 2014, the use of UAVs rapidly expanded, giving weak states and non-state actors an asymmetric advantage over their technologically superior foes. This asymmetry led the Department of Defense (DOD) and the Department of Homeland Security (DHS) to spend vast sums of money on counter-unmanned aircraft systems (C-UAS). Despite the market density, many C-UAS technologies use expensive, bulky, and high-power-consuming electronic attack methods for ground-to-air interdiction. This thesis outlines the current technology used for C-UAS and proposes a defense-in-depth framework using airborne C-UAS patrols outfitted with cyber-attack capabilities. Using aerial interdiction, this thesis develops a novel C-UAS device called the Detachable Drone Hijacker—a low-size, weight, and power C-UAS device designed to deliver cyber-attacks against commercial UAVs using the IEEE 802.11 wireless communication specification. The experimentation results show that the Detachable Drone Hijacker, which weighs 400 grams, consumes one Watt of power, and costs $250, can interdict adversarial UAVs with no unintended collateral damage. This thesis recommends that the DOD and DHS incorporates aerial interdiction to support its C-UAS defense-in-depth, using technologies similar to the Detachable Drone Hijacker.DASN-OE, Washington DC, 20310Captain, United States Marine CorpsApproved for public release. Distribution is unlimited

    Chinese Benteng Women’s Participation in Local Development Affairs in Indonesia: Appropriate means for struggle and a pathway to claim citizen’ right?

    Get PDF
    It had been more than two decades passing by aftermath the devastating Asia’s Financial Crisis in 1997, subsequently followed by Suharto’s step down from his presidential throne which he occupied for more than three decades. The financial turmoil turned to a political disaster furthermore has led to massive looting that severely impacted Indonesians of Chinese descendant, including unresolved mystery of the most atrocious sexual violation against women and covert killings of students and democracy activists in this country. Since then, precisely aftermath May 1998, which publicly known as “Reformasi”1, Indonesia underwent political reform that eventually corresponded positively to its macroeconomic growth. Twenty years later, in 2018, Indonesia captured worldwide attention because it has successfully hosted two internationally renowned events, namely the Asian Games 2018 – the most prestigious sport events in Asia – conducted in Jakarta and Palembang; and the IMF/World Bank Annual Meeting 2018 in Bali. Particularly in the IMF/World Bank Annual Meeting, this event has significantly elevated Indonesia’s credibility and international prestige in the global economic powerplay as one of the nations with promising growth and openness. However, the narrative about poverty and inequality, including increasing racial tension, religious conservatism, and sexual violation against women are superseded by friendly climate for foreign investment and eventually excessive glorification of the nation’s economic growth. By portraying the image of promising new economic power, as rhetorically promised by President Joko Widodo during his presidential terms, Indonesia has swept the growing inequality in this highly stratified society that historically compounded with religious and racial tension under the carpet of digital economy.Arte y Humanidade

    Developing automated meta-research approaches in the preclinical Alzheimer's disease literature

    Get PDF
    Alzheimer’s disease is a devastating neurodegenerative disorder for which there is no cure. A crucial part of the drug development pipeline involves testing therapeutic interventions in animal disease models. However, promising findings in preclinical experiments have not translated into clinical trial success. Reproducibility has often been cited as a major issue affecting biomedical research, where experimental results in one laboratory cannot be replicated in another. By using meta-research (research on research) approaches such as systematic reviews, researchers aim to identify and summarise all available evidence relating to a specific research question. By conducting a meta-analysis, researchers can also combine the results from different experiments statistically to understand the overall effect of an intervention and to explore reasons for variations seen across different publications. Systematic reviews of the preclinical Alzheimer’s disease literature could inform decision making, encourage research improvement, and identify gaps in the literature to guide future research. However, due to the vast amount of potentially useful evidence from animal models of Alzheimer’s disease, it remains difficult to make sense of and utilise this data effectively. Systematic reviews are common practice within evidence based medicine, yet their application to preclinical research is often limited by the time and resources required. In this thesis, I develop, build-upon, and implement automated meta-research approaches to collect, curate, and evaluate the preclinical Alzheimer’s literature. I searched several biomedical databases to obtain all research relevant to Alzheimer’s disease. I developed a novel deduplication tool to automatically identify and remove duplicate publications identified across different databases with minimal human effort. I trained a crowd of reviewers to annotate a subset of the publications identified and used this data to train a machine learning algorithm to screen through the remaining publications for relevance. I developed text-mining tools to extract model, intervention, and treatment information from publications and I improved existing automated tools to extract reported measures to reduce the risk of bias. Using these tools, I created a categorised database of research in transgenic Alzheimer’s disease animal models and created a visual summary of this dataset on an interactive, openly accessible online platform. Using the techniques described, I also identified relevant publications within the categorised dataset to perform systematic reviews of two key outcomes of interest in transgenic Alzheimer’s disease models: (1) synaptic plasticity and transmission in hippocampal slices and (2) motor activity in the open field test. Over 400,000 publications were identified across biomedical research databases, with 230,203 unique publications. In a performance evaluation across different preclinical datasets, the automated deduplication tool I developed could identify over 97% of duplicate citations and a had an error rate similar to that of human performance. When evaluated on a test set of publications, the machine learning classifier trained to identify relevant research in transgenic models performed was highly sensitive (captured 96.5% of relevant publications) and excluded 87.8% of irrelevant publications. Tools to identify the model(s) and outcome measure(s) within the full-text of publications may reduce the burden on reviewers and were found to be more sensitive than searching only the title and abstract of citations. Automated tools to assess risk of bias reporting were highly sensitive and could have the potential to monitor research improvement over time. The final dataset of categorised Alzheimer’s disease research contained 22,375 publications which were then visualised in the interactive web application. Within the application, users can see how many publications report measures to reduce the risk of bias and how many have been classified as using each transgenic model, testing each intervention, and measuring each outcome. Users can also filter to obtain curated lists of relevant research, allowing them to perform systematic reviews at an accelerated pace with reduced effort required to search across databases, and a reduced number of publications to screen for relevance. Both systematic reviews and meta-analyses highlighted failures to report key methodological information within publications. Poor transparency of reporting limited the statistical power I had to understand the sources of between-study variation. However, some variables were found to explain a significant proportion of the heterogeneity. Transgenic animal model had a significant impact on results in both reviews. For certain open field test outcomes, wall colour of the open field arena and the reporting of measures to reduce the risk of bias were found to impact results. For in vitro electrophysiology experiments measuring synaptic plasticity, several electrophysiology parameters, including magnesium concentration of the recording solution, were found to explain a significant proportion of the heterogeneity. Automated meta-research approaches and curated web platforms summarising preclinical research could have the potential to accelerate the conduct of systematic reviews and maximise the potential of existing evidence to inform translation

    The stuff of strategy: the potential of the material turn in strategy studies

    Get PDF
    This thesis explores the potential of the material turn in strategy studies to explore how nonhuman ‘things’ contribute to strategy production. Drawing on the ontologies and methodologies of the strategy-as-practice and actor-network theory domains, the empirical research informing this thesis is an immersive mixed methods ethnographic study in a higher education school of art and design conducted over a period of 24 months. The study combines observation and a qualitative interview protocol to build four explorative case study narratives that consider various aspects of material agency in strategy production. Analysis and discussion inform a re-theorising of strategy production that foregrounds the agency of materials beyond that of human intent, providing a counterpoint to prevailing approaches that centre the affordances ‘things’ offer to human action and suggesting instead a novel extension to strategy studies that emphasises emancipatory critique of normative organisational practices and ontologies
    corecore