14,369 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
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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
Chiral active fluids: Odd viscosity, active turbulence, and directed flows of hydrodynamic microrotors
While the number of publications on rotating active matter has rapidly increased in recent years, studies on purely hydrodynamically interacting rotors on the microscale are still rare, especially from the perspective of particle based hydrodynamic simulations. The work presented here targets to fill this gap. By means of high-performance computer simulations, performed in a highly parallelised fashion on graphics processing units, the dynamics of ensembles of up to 70,000 rotating colloids immersed in an explicit mesoscopic solvent consisting out of up to 30 million fluid particles, are investigated. Some of the results presented in this thesis have been worked out in collaboration with experimentalists, such that the theoretical considerations developed in this thesis are supported by experiments, and vice versa. The studied system, modelled in order to resemble the essential physics of the experimentally realisable system, consists out of rotating magnetic colloidal particles, i.e., (micro-)rotors, rotating in sync to an externally applied magnetic field, where the rotors solely interact via hydrodynamic and steric interactions. Overall, the agreement between simulations and experiments is very good, proving that hydrodynamic interactions play a key role in this and related systems.
While already an isolated rotating colloid is driven out of equilibrium, only collections of two or more rotors have experimentally shown to be able to convert the rotational energy input into translational dynamics in an orbital rotating fashion. The rotating colloids inject circular flows into the fluid, such that detailed balance is broken, and it is not a priori known whether equilibrium properties of colloids can be extended to isolated rotating colloids. A joint theoretical and experimental analysis of isolated, pairs, and small groups of hydrodynamically interacting rotors is given in chapter 2. While the translational dynamics of isolated rotors effectively resemble the dynamics of non-rotating colloids, the orbital rotation of pairs of rotors can be described with leading order hydrodynamics and a two-dimensional analogy of Faxén’s law is derived.
In chapter 3, a homogeneously distributed ensemble of rotors (bulk) as a realisation of a chiral active fluid is studied and it is explicitly shown computationally and experimentally that it carries odd viscosity. The mutual orbital translation of rotors and an increase of the effective solvent viscosity with rotor density lead to a non-monotonous behaviour of the average translational velocity. Meanwhile, the rotor suspension bears a finite osmotic compressibility resulting from the long-ranged nature of hydrody- namic interactions such that rotational and odd stresses are transmitted through the solvent also at small and intermediate rotor densities. Consequently, density inhomogeneities predicted for chiral active fluids with odd viscosity can be found and allow for an explicit measurement of odd viscosity in simulations and experiments. At intermediate densities, the collective dynamics shows the emergence of multi-scale vortices and chaotic motion which is identified as active turbulence with a self-similar power-law decay in the energy spectrum, showing that the injected energy on the rotor scale is transported to larger scales, similar to the inverse energy cascade of clas- sical two-dimensional turbulence. While either odd viscosity or active turbulence have been reported in chiral active matter previously, the system studied here shows that the emergence of both simultaneously is possible resulting from the osmotic compressibility and hydrodynamic mediation of odd and active stresses. The collective dynamics of colloids rotating out of phase, i.e., where a constant torque instead of a constant angular velocity is applied, is shown to be qualitatively very similar. However, at smaller densities, local density inhomogeneities imply position dependent angular velocities of the rotors resulting from inter-rotor friction.
While the friction of a quasi-2D layer of active colloids with the substrate is often not easily modifiable in experiments, the incorporation of substrate friction into the simulation models typically implies a considerable increase in computational effort. In chapter 4, a very efficient way of incorporating the friction with a substrate into a two-dimensional multiparticle collision dynamics solvent is introduced, allowing for an explicit investigation of the influences of substrate on active dynamics. For the rotor fluid, it is explicitly shown that the influence of the substrate friction results in a cutoff of the hydrodynamic interaction length, such that the maximum size of the formed vortices is controlled by the substrate friction, also resulting in a cutoff in the energy spectrum, because energy is taken out of the system at the respective length. These findings are in agreement with the experiments.
Since active particles in confinement are known to organise in states of collective dynamics, ensembles of rotationally actuated colloids are studied in circular confinement and in the presence of periodic obstacle lattices in chapters 5 and 6, respectively. The results show that the chaotic active turbulent transport of rotors in suspension can be enhanced and guided resulting from edge flows generated at the boundaries, as has recently been reported for a related chiral active system. The consequent collective rotor dynamics can be regarded as a superposition of active turbulent and imposed flows, leading to on average stationary flows. In contrast to the bulk dynamics, the imposed flows inject additional energy into the system on the long length scales, and the same scaling behaviour of the energy spectrum as in bulk is only obtained if the energy injection scales, due to the mutual generation of rotor translational dynamics throughout the system and the edge flows, are well separated. The combination of edge flow and entropic layering at the boundaries leads to oscillating hydrodynamic stresses and consequently to an oscillating vorticity profile. In the presence of odd viscosity, this consequently leads to non-trivial steady-state density modulations at the boundary, resulting from a balance of osmotic pressure and odd stresses.
Relevant for the efficient dispersion and mixing of inert particles on the mesoscale by means of active turbulent mixing powered by rotors, a study of the dynamics of a binary mixture consisting out of rotors and passive particles is presented in chapter 7. Because the rotors are not self-propelled, but the translational dynamics is induced by the surrounding rotors, the passive particles, which do not inject further energy into the system, are transported according to the same mechanism as the rotors. The collective dynamics thus resembles the pure rotor bulk dynamics at the respective density of only rotors. However, since no odd stresses act between the passive particles, only mutual rotor interactions lead to odd stresses leading to the accumulation of rotors in the regions of positive vorticity. This density increase is associated with a pressure increase, which balances the odd stresses acting on the rotors. However, the passive particles are only subject to the accumulation induced pressure increase such that these particles are transported into the areas of low rotor concentration, i.e., the regions of negative vorticity. Under conditions of sustained vortex flow, this results in segregation of both particle types.
Since local symmetry breaking can convert injected rotational into translational energy, microswimmers can be constructed out of rotor materials when a suitable breaking of symmetry is kept in the vicinity of a rotor. One hypothetical realisation, i.e., a coupled rotor pair consisting out of two rotors of opposite angular velocity and of fixed distance, termed a birotor, are studied in chapter 8. The birotor pumps the fluid into one direction and consequently translates into the opposite direction, and creates a flow field reminiscent of a source doublet, or sliplet flow field. Fixed in space the birotor might be an interesting realisation of a microfluidic pump. The trans- lational dynamics of a birotor can be mapped onto the active Brownian particle model for single swimmers. However, due to the hydrodynamic interactions among the rotors, the birotor ensemble dynamics do not show the emergence of stable motility induced clustering. The reason for this is the flow created by birotor in small aggregates which effectively pushes further arriving birotors away from small aggregates, which eventually are all dispersed by thermal fluctuations
Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021
É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio
Boosting the Cycle Counting Power of Graph Neural Networks with I-GNNs
Message Passing Neural Networks (MPNNs) are a widely used class of Graph
Neural Networks (GNNs). The limited representational power of MPNNs inspires
the study of provably powerful GNN architectures. However, knowing one model is
more powerful than another gives little insight about what functions they can
or cannot express. It is still unclear whether these models are able to
approximate specific functions such as counting certain graph substructures,
which is essential for applications in biology, chemistry and social network
analysis. Motivated by this, we propose to study the counting power of Subgraph
MPNNs, a recent and popular class of powerful GNN models that extract rooted
subgraphs for each node, assign the root node a unique identifier and encode
the root node's representation within its rooted subgraph. Specifically, we
prove that Subgraph MPNNs fail to count more-than-4-cycles at node level,
implying that node representations cannot correctly encode the surrounding
substructures like ring systems with more than four atoms. To overcome this
limitation, we propose I-GNNs to extend Subgraph MPNNs by assigning
different identifiers for the root node and its neighbors in each subgraph.
I-GNNs' discriminative power is shown to be strictly stronger than Subgraph
MPNNs and partially stronger than the 3-WL test. More importantly, I-GNNs
are proven capable of counting all 3, 4, 5 and 6-cycles, covering common
substructures like benzene rings in organic chemistry, while still keeping
linear complexity. To the best of our knowledge, it is the first linear-time
GNN model that can count 6-cycles with theoretical guarantees. We validate its
counting power in cycle counting tasks and demonstrate its competitive
performance in molecular prediction benchmarks
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
Coloniality and the Courtroom: Understanding Pre-trial Judicial Decision Making in Brazil
This thesis focuses on judicial decision making during custody hearings in Rio de Janeiro, Brazil. The impetus for the study is that while national and international protocols mandate the use of pre-trial detention only as a last resort, judges continue to detain people pre-trial in large numbers. Custody hearings were introduced in 2015, but the initiative has not produced the reduction in pre-trial detention that was hoped. This study aims to understand what informs judicial decision making at this stage. The research is approached through a decolonial lens to foreground legacies of colonialism, overlooked in mainstream criminological scholarship. This is an interview-based study, where key court actors (judges, prosecutors, and public defenders) and subject matter specialists were asked about influences on judicial decision making. Interview data is complemented by non-participatory observation of custody hearings. The research responds directly to Aliverti et al.'s (2021) call to ‘decolonize the criminal question’ by exposing and explaining how colonialism informs criminal justice practices. Answering the call in relation to judicial decision making, findings provide evidence that colonial-era assumptions, dynamics, and hierarchies were evident in the practice of custody hearings and continue to inform judges’ decisions, thus demonstrating the coloniality of justice. This study is significant for the new empirical data presented and theoretical innovation is also offered via the introduction of the ‘anticitizen’. The concept builds on Souza’s (2007) ‘subcitizen’ to account for the active pursuit of dangerous Others by judges casting themselves as crime fighters in a modern moral crusade. The findings point to the limited utility of human rights discourse – the normative approach to influencing judicial decision making around pre-trial detention – as a plurality of conceptualisations compete for dominance. This study has important implications for all actors aiming to reduce pre-trial detention in Brazil because unless underpinning colonial logics are addressed, every innovation risks becoming the next lei para inglês ver (law [just] for the English to see)
RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s 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 Parkinson’s 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 3’ untranslated region (3’-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
Proof of Concept of Therapeutic Gene Modulation of MBNL1/2 in Myotonic Dystrophy
La distrofia miotónica tipo 1 es una enfermedad genética rara multisistémica que afecta a 1 de cada 3000-8000 personas. La causa molecular de la enfermedad proviene de repeticiones tóxicas “CTG” en el gen DMPK (DM Protein Kinase). Tras la transcripción, estas repeticiones forman una estructura de horquilla que se une con alta afinidad a la familia de proteínas MBNL (Muscleblind-like) que agota su función de regulación de la poliadenilación y el splicing alternativo postranscripcional en numerosos transcritos. La pérdida de función de MBNL provoca una cascada de efectos posteriores, que eventualmente conducen a síntomas clínicos que incluyen miotonía, debilidad y atrofia muscular, cataratas, disfunción cardíaca y trastorno cognitivo. La restauración de la función de la proteína MBNL es clave para aliviar los síntomas debilitantes de esta enfermedad. Se han utilizado oligonucleótidos antisentido (AON) para apuntar a las repeticiones de DMPK y liberar MBNL del secuestro, lo que da como resultado resultados terapéuticos prometedores en modelos celulares y animales de la enfermedad. Otro factor que interviene en la pérdida de función de las proteínas MBNL son los miRNAs que regulan su traducción. Aquí se muestra el uso de AON dirigidos a la actividad de miR-23b y miR-218, que se ha demostrado previamente que regulan directamente MBNL1 y MBNL2. Estos antimiRs recibieron modificaciones FANA para aumentar su entrega en las células y reducir la toxicidad. También se probaron los AON, denominados blockmiRs, que se unen de manera complementaria a los sitios de unión confirmados de miR-23b y miR-218 en los 3'-UTR de las transcripciones de MBNL1 y MBNL2. De esta manera, los miRNAs no pueden unirse y regular la traducción de MBNL, lo que aumenta la cantidad de proteína MBNL producida en una célula deficiente. Aquí se propone el uso de AON de nuevo diseño dirigidos a la actividad de miR-23b y miR-218 para regular MBNL1 y MBNL2 a través de (1) exploración del bloqueo de miRNA a través de FANA-antimiR AON in vitro, (2) exploración del bloqueo del sitio de unión de miRNA a través de la estrategia blockmiR in vitro e in vivo con el uso de modificaciones químicas de LNA, y (3) mejora de la química de la estrategia blockmiR mediante el uso de tecnología de péptidos de penetración celular in vitro e in vivo.Myotonic Dystrophy Type 1 is a multi-systemic rare genetic disease affecting 1 in 3000-8000 people. The molecular cause of the disease stems from toxic “CTG” repetitions in the DMPK (DM Protein Kinase) gene. Upon transcription, these repetitions form a hairpin structure that binds with high affinity to the MBNL (Muscleblind-like) family of proteins depleting their function of post-transcriptional alternative splicing and polyadenylation regulation on numerous transcripts. MBNL loss-of-function causes a cascade of downstream effects, which eventually lead to clinical symptoms including myotonia, muscle weakness and atrophy, cataracts, cardiac dysfunction, and cognitive disorder. The restoration of MBNL protein function is key to relieving the debilitating symptoms of this disease. Antisense oligonucleotides (AONs) have been used to target the DMPK repeats and release MBNL from sequestration resulting in promising therapeutic results in cellular and animal models of the disease. Another factor playing a role in the loss-of-function of MBNL proteins are the miRNAs that regulate their translation. Here is shown the use of AONs targeting miR-23b and miR-218 activity, which have been previously shown to directly regulate MBNL1 and MBNL2. These antimiRs were given FANA modifications to increase their delivery in cells and lower toxicity. Also tested are AONs, termed blockmiRs, that complementary bind to the confirmed binding sites of miR-23b and miR-218 in the 3’-UTRs of MBNL1 and MBNL2 transcripts. In this way, the miRNAs are unable to bind and regulate the translation of MBNL thereby augmenting the amount of MBNL protein made in an otherwise deficient cell. Proposed here is the use of newly designed AONs targeting miR-23b and miR-218 activity in order to regulate MBNL1 and MBNL2 through (1) exploration of miRNA blocking through FANA-antimiR AONs in vitro, (2) exploration of miRNA binding site blocking through blockmiR strategy in vitro and in vivo with the use of LNA chemical modifications, and (3) improvement of the chemistry of the blockmiR strategy through the use of cell penetrating peptide technology in vitro and in vivo
Innate immunity and metabolism in the bovine ovarian follicle
Postpartum uterine disease in dairy cows is associated with reduced fertility. One of the first and most prevalent bacteria associated with uterine disease is Escherichia coli. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the ovarian follicular fluid of animals with uterine disease. The granulosa cells of the ovarian follicle respond to LPS by secreting pro-inflammatory cytokines, such as interleukin (IL)-1a, IL-1b and IL-8, and oocyte health is perturbed. Dairy cows also experience metabolic energy stress in the postpartum period, which is associated with an increased risk of developing uterine disease and ovarian dysfunction. This thesis explored the crosstalk between innate immunity and metabolic energy stress in bovine granulosa cells and cumulus-oocyte complex. Firstly, we found that glycolysis, AMP-activated protein kinase and the mechanistic target of rapamycin, regulate the innate immune responses to LPS in granulosa cells isolated from bovine ovarian follicles. Activation of AMP-activated protein kinase decreased the LPS-induced secretion of IL-1a, IL-1b, and IL8, and was associated with shortened duration of ERK1/2 and JNK phosphorylation. Next, we found that decreasing the availability of cholesterol or inhibiting cholesterol biosynthesis using short-interfering RNA impaired the LPS-induced secretion of IL-1a and IL-1b by granulosa cells. Furthermore, metabolic energy stress or inhibiting cholesterol biosynthesis in the bovine cumulus-oocyte complex modulated the innate immune responses to LPS, and perturbed meiotic progression during in vitro maturation. Finally, we explored an in vivo model of uterine disease in heifers, using RNAseq to investigate alterations to the transcriptome of the reproductive tract. We found that uterine disease altered the transcriptome of the endometrium, oviduct, granulosa cells and oocyte, several months after bacterial infusion; these changes were most evident in the granulosa cells and oocyte of the ovarian follicle. The findings from this thesis imply that there is crosstalk between innate immunity and metabolism in the bovine ovarian follicle
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