12,170 research outputs found
Meso-scale FDM material layout design strategies under manufacturability constraints and fracture conditions
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
Minimum income support systems as elements of crisis resilience in Europe: Final Report
Mindestsicherungssysteme dienen in den meisten entwickelten Wohlfahrtsstaaten als Sicherheitsnetz letzter Instanz. Dementsprechend spielen sie gerade in wirtschaftlichen Krisenzeiten eine besondere Rolle. Inwieweit Mindestsicherungssysteme in Zeiten der Krise beansprucht werden, hĂ€ngt auch von der AusprĂ€gung vorgelagerter Sozialschutzsysteme ab. Diese Studie untersucht die Bedeutung von Systemen der Mindestsicherung sowie vorgelagerter Systeme wie Arbeitslosenversicherung, Kurzarbeit und arbeitsrechtlichem Bestandsschutz fĂŒr die Krisenfestigkeit in Europa. Im Kontext der Finanzkrise von 2008/2009 und der Corona-Krise wird die FĂ€higkeit sozialpolitischer MaĂnahmen untersucht, Armut und EinkommensÂverluste einzudĂ€mmen und gesellschaftliche Ausgrenzung zu vermeiden. Die Studie setzt dabei auf quantitative und qualitative Methoden, etwa multivariate Analysen, Mikrosimulationsmethoden sowie eingehende Fallstudien der LĂ€nder DĂ€nemark, Frankreich, Irland, Polen und Spanien, die fĂŒr unterschiedliche Typen von Wohlfahrtsstaaten stehen.The aim of this study is to analyse the role of social policies in different European welfare states regarding minimum income protection and active inclusion. The core focus lies on crisis resilience, i.e. the capacity of social policy arrangements to contain poverty and inequality and avoid exclusion before, during and after periods of economic shocks. To achieve this goal, the study expands its analytical focus to include other tiers of social protection, in particular upstream systems such as unemployment insurance, job retention and employment protection, as they play an additional and potentially prominent role in providing income and job protection in situations of crisis. A mixed-method approach is used that combines quantitative and qualitative research, such as descriptive and multivariate quantitative analyses, microsimulation methods and in-depth case studies. The study finds consistent differences in terms of crisis resilience across countries and welfare state types. In general, Nordic and Continental European welfare states with strong upstream systems and minimum income support (MIS) show better outcomes in core socio-economic outcomes such as poverty and exclusion risks. However, labour market integration shows some dualisms in Continental Europe. The study shows that MIS holds particular importance if there are gaps in upstream systems or cases of severe and lasting crises
Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future
Respiratory diseases are pathological conditions that affect airways, hampering breathing and causing high mortality. In particular, asthma and allergic rhinitis (AR) are two of the most common airway diseases that affect millions of people and have a high prevalence in childhood and adulthood. Asthma is a heterogeneous chronic inflammatory disease characterized by wheezing, chest tightness, shortness of breath, and cough. AR occurs with rhinorrhea, nasal congestion, and sneezing. Indeed, these pathologies share common physiopathological mechanisms such as airway hyperresponsiveness and similar immunopathology such as tissue eosinophilia and T-helper type 2 inflammation. Moreover, AR can be an important risk factor for suffering asthma. Thus, early diagnosis and effective treatment are crucial to improving the health and quality of life of these patients. Classical drugs such as corticosteroids have been used; however, in the last decades, efforts to improve treatments have increased, focusing on biological agents and specific allergen immunotherapy development. Moreover, more precise diagnostic tools have been elaborated, besides classical methods (medical history, physical examination, and pulmonary function tests), such as basophil activation test, and specific cellular and molecular biomarkers (microRNAs, sputum/blood eosinophils, IgE serum, and periostin levels). Therefore, in this review, we compile all these important issues for managing asthma and AR.Espada-SĂĄnchez M, SĂĄenz de Santa MarĂa R, MartĂn-Astorga MdC, LebrĂłn-MartĂn C, Delgado MJ, Eguiluz-Gracia I, RondĂłn C, Mayorga C, Torres MJ, Aranda CJ, Cañas JA. Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future. Applied Sciences. 2023; 13(3):1273. https://doi.org/10.3390/app1303127
The place where curses are manufactured : four poets of the Vietnam War
The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human
feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences
Nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis
Dietary nitrate lowers the oxygen cost of submaximal exercise, but precise mechanistic insight into how this occurs is lacking. Research suggests that dietary nitrate may render oxidative ATP synthesis more efficient, but evidence is inconclusive at present. This thesis aimed to establish how nitrite (a reduced form of nitrate) affects the bioenergetics of cultured skeletal muscle cells. Comparison between the acute effects of nitrite and insulin, a hormonal regulator of muscle function that increases mitochondrial efficiency, was explored to assess possible mechanistic overlap. Calculation of real-time intracellular ATP synthesis rates from simultaneous oxygen consumption and medium acidification measurements revealed the effects of sodium nitrite and insulin on intact rat (L6) myoblasts and myotubes. These extracellular flux data were also used to determine how mitochondrial and glycolytic ATP supply is used to fuel ATP-demanding processes. The data presented in this thesis revealed that both nitrite and insulin acutely stimulate glycolytic ATP synthesis. This stimulation occurs without significant mitochondrial ATP supply changes, thus increasing the glycolytic index of myocytes. Consequently, nitrite and insulin lower the oxygen cost of cellular ATP supply. Notably, insulin lowers oxygen consumption linked to mitochondrial proton leak, thus increasing mitochondrial efficiency. Nitrite does not improve coupling efficiency in myoblasts or myotubes. Further investigations revealed that stimulation of glycolytic ATP supply is not secondary to increased glucose availability. In myotubes, glycolytic stimulation persists in the presence of a mitochondrial uncoupler, suggesting that glycolysis is increased directly. In myoblasts, stimulation is annulled by uncoupler, suggesting that glycolysis increases indirectly, via increased ATP consumption. The molecular targets of nitrite and insulin remain unclear, but the data exclude stimulation of protein synthesis. Together, the data demonstrate that nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis. The data inform the ongoing debate regarding the mechanism by which dietary nitrate lowers the oxygen cost of exercise, suggesting a push toward a more glycolytic phenotype. Such mechanistic insight is crucial for achieving the full translational potential of dietary nitrate
Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines
Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces
Building body identities - exploring the world of female bodybuilders
This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinsonâs disease targeting RNA/HuR complexes
MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy.
HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinsonâs disease (PD).
PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies.
In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD.
To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells.
To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3â untranslated region (3â-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression.
In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies
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