6,269 research outputs found

    Meso-scale FDM material layout design strategies under manufacturability constraints and fracture conditions

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    In the manufacturability-driven design (MDD) perspective, manufacturability of the product or system is the most important of the design requirements. In addition to being able to ensure that complex designs (e.g., topology optimization) are manufacturable with a given process or process family, MDD also helps mechanical designers to take advantage of unique process-material effects generated during manufacturing. One of the most recognizable examples of this comes from the scanning-type family of additive manufacturing (AM) processes; the most notable and familiar member of this family is the fused deposition modeling (FDM) or fused filament fabrication (FFF) process. This process works by selectively depositing uniform, approximately isotropic beads or elements of molten thermoplastic material (typically structural engineering plastics) in a series of pre-specified traces to build each layer of the part. There are many interesting 2-D and 3-D mechanical design problems that can be explored by designing the layout of these elements. The resulting structured, hierarchical material (which is both manufacturable and customized layer-by-layer within the limits of the process and material) can be defined as a manufacturing process-driven structured material (MPDSM). This dissertation explores several practical methods for designing these element layouts for 2-D and 3-D meso-scale mechanical problems, focusing ultimately on design-for-fracture. Three different fracture conditions are explored: (1) cases where a crack must be prevented or stopped, (2) cases where the crack must be encouraged or accelerated, and (3) cases where cracks must grow in a simple pre-determined pattern. Several new design tools, including a mapping method for the FDM manufacturability constraints, three major literature reviews, the collection, organization, and analysis of several large (qualitative and quantitative) multi-scale datasets on the fracture behavior of FDM-processed materials, some new experimental equipment, and the refinement of a fast and simple g-code generator based on commercially-available software, were developed and refined to support the design of MPDSMs under fracture conditions. The refined design method and rules were experimentally validated using a series of case studies (involving both design and physical testing of the designs) at the end of the dissertation. Finally, a simple design guide for practicing engineers who are not experts in advanced solid mechanics nor process-tailored materials was developed from the results of this project.U of I OnlyAuthor's request

    Graft-Specific Surgical and Rehabilitation Considerations for Anterior Cruciate Ligament Reconstruction with the Quadriceps Tendon Autograft

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    Anterior cruciate ligament reconstruction (ACLR) with a bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autograft has traditionally been the preferred surgical treatment for patients returning to Level 1 sports. More recently, international utilization of the quadriceps tendon (QT) autograft for primary and revision ACLR has increased in popularity. Recent literature suggests that ACLR with the QT may yield less donor site morbidity than the BPTB and better patient-reported outcomes than the HT. Additionally, anatomic and biomechanical studies have highlighted the robust properties of the QT itself, with superior levels of collagen density, length, size, and load-to-failure strength compared to the BPTB. Although previous literature has described rehabilitation considerations for the BPTB and HT autografts, there is less published with respect to the QT. Given the known impact of the various ACLR surgical techniques on postoperative rehabilitation, the purpose of this clinical commentary is to present the procedure-specific surgical and rehabilitation considerations for ACLR with the QT, as well as further highlight the need for procedure-specific rehabilitation strategies after ACLR by comparing the QT to the BPTB and HT autografts. # Level of Evidence Level

    In vitro investigation of the effect of disulfiram on hypoxia induced NFκB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines

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    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM. This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFκB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFκB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFκB in maintaining GSC phenotypes. The study also highlighted the significance of NFκB in driving chemoresistance, invasiveness, and the potential role of NFκB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration. In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFκB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations. DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients

    The Adirondack Chronology

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    The Adirondack Chronology is intended to be a useful resource for researchers and others interested in the Adirondacks and Adirondack history.https://digitalworks.union.edu/arlpublications/1000/thumbnail.jp

    The Role of English and Welsh INGOs: A Field Theory-Based Exploration of the Sector

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    This thesis takes a field theory-based approach to exploring the role of English and Welsh international non-governmental organisations (INGOs), using the lens of income source form. First, the thesis presents new income source data drawn from 933 Annual Accounts published by 316 INGOs over three years (2015-2018). The research then draws on qualitative data from 90 Leaders' letters include within the Annual Reports published by 39 INGOS, as well as supplementary quantitative and qualitative data, to explore the ways in which INGOs represent their role. Analysis of this income source data demonstrates that government funding is less important to most INGOs than has previously been assumed, while income from individuals is more important than has been recognised in the extant development studies literature. Funding from other organisations within the voluntary sector is the third most important source of income for these INGOs, while income from fees and trading is substantially less important than the other income source forms. Using this income source data in concert with other quantitative data on INGO characteristics as well as qualitative data drawn from the Leaders' letters, I then show that the English and Welsh INGO sector is a heterogenous space, divided into multiple fields. The set of fields identified by this thesis is arranged primarily around income source form, which is also associated with size, religious affiliation, and activities of focus and ways of working. As Bourdieusian field theory suggests, within these fields individual INGOs are engaged in an ongoing struggle for position: competing to demonstrate their maximal possession of the symbolic capitals they perceive to be valued by (potential) donors to that field. Further analysis of these Leaders' letters, alongside additional Annual Reports and Accounts data, also reveals a dissonance in the way in which INGOs describe their relationship with local partners in these different communication types. While these Leaders' letters and narrative reports tell stories of collaborative associations with locally-based partners, this obscures the nature of these relationships as competitive and hierarchical. The thesis draws on the above findings to reflect on the role of INGOs as suggested in the extant literature. This discussion highlights how the various potential INGO fields identified are associated with differing theoretical roles for INGOs. Finally, the thesis considers how INGO role representations continue to contribute to unequal power relations between INGOs and their partners

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

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    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

    A comprehensive review on laser powder bed fusion of steels : processing, microstructure, defects and control methods, mechanical properties, current challenges and future trends

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    Laser Powder Bed Fusion process is regarded as the most versatile metal additive manufacturing process, which has been proven to manufacture near net shape up to 99.9% relative density, with geometrically complex and high-performance metallic parts at reduced time. Steels and iron-based alloys are the most predominant engi-neering materials used for structural and sub-structural applications. Availability of steels in more than 3500 grades with their wide range of properties including high strength, corrosion resistance, good ductility, low cost, recyclability etc., have put them in forefront of other metallic materials. However, LPBF process of steels and iron-based alloys have not been completely established in industrial applications due to: (i) limited insight available in regards to the processing conditions, (ii) lack of specific materials standards, and (iii) inadequate knowledge to correlate the process parameters and other technical obstacles such as dimensional accuracy from a design model to actual component, part variability, limited feedstock materials, manual post-processing and etc. Continued efforts have been made to address these issues. This review aims to provide an overview of steels and iron-based alloys used in LPBF process by summarizing their key process parameters, describing thermophysical phenomena that is strongly linked to the phase transformation and microstructure evolution during solidifica-tion, highlighting metallurgical defects and their potential control methods, along with the impact of various post-process treatments; all of this have a direct impact on the mechanical performance. Finally, a summary of LPBF processed steels and iron-based alloys with functional properties and their application perspectives are presented. This review can provide a foundation of knowledge on LPBF process of steels by identifying missing information from the existing literature

    Industry 4.0: product digital twins for remanufacturing decision-making

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    Currently there is a desire to reduce natural resource consumption and expand circular business principles whilst Industry 4.0 (I4.0) is regarded as the evolutionary and potentially disruptive movement of technology, automation, digitalisation, and data manipulation into the industrial sector. The remanufacturing industry is recognised as being vital to the circular economy (CE) as it extends the in-use life of products, but its synergy with I4.0 has had little attention thus far. This thesis documents the first investigating into I4.0 in remanufacturing for a CE contributing a design and demonstration of a model that optimises remanufacturing planning using data from different instances in a product’s life cycle. The initial aim of this work was to identify the I4.0 technology that would enhance the stability in remanufacturing with a view to reducing resource consumption. As the project progressed it narrowed to focus on the development of a product digital twin (DT) model to support data-driven decision making for operations planning. The model’s architecture was derived using a bottom-up approach where requirements were extracted from the identified complications in production planning and control that differentiate remanufacturing from manufacturing. Simultaneously, the benefits of enabling visibility of an asset’s through-life health were obtained using a DT as the modus operandi. A product simulator and DT prototype was designed to use Internet of Things (IoT) components, a neural network for remaining life estimations and a search algorithm for operational planning optimisation. The DT was iteratively developed using case studies to validate and examine the real opportunities that exist in deploying a business model that harnesses, and commodifies, early life product data for end-of-life processing optimisation. Findings suggest that using intelligent programming networks and algorithms, a DT can enhance decision-making if it has visibility of the product and access to reliable remanufacturing process information, whilst existing IoT components provide rudimentary “smart” capabilities, but their integration is complex, and the durability of the systems over extended product life cycles needs to be further explored

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

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    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
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