379 research outputs found
FACTOR XI ACTIVATION AND INHIBITION IN CATHETER-INDUCED CLOTTING
No full textIf you have comments or suggestions for improvements, please direct these to the corresponding author, Ruiqi Yin ([email protected]).Thrombosis, or blood clot formation in vessels, is responsible for 1 in 4 deaths in Canada and worldwide. Patients with acute coronary syndrome (ACS), atrial fibrillation (AF), or cancer often require central venous catheters (CVCs) for medical access, such as receiving chemotherapy, drugs, and nutrition. These catheters, like peripherally inserted central catheters (PICC) and implanted ports, are associated with an increased risk of thrombosis, as clots tend to form inside the catheters and block the vessels. Vascular blockages cause severe complications like deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, effective and safe anticoagulants are essential to manage and prevent catheter-induced clotting. Factor (F) XI in the contact pathway of coagulation has emerged as a promising target for anticoagulant therapy because FXI is key for blood clot formation but is not essential in normal blood clotting. Consequently, FXI inhibitors have become a safer alternative to currently available anticoagulants. FXI can be autoactivated by negatively charged surfaces like polyphosphate (polyP), released from activated platelets, or synthetic surfaces like catheters. Thus, FXI is a root cause of catheter- and polyP-induced clotting. Milvexian and abelacimab, both FXI inhibitors, are currently undergoing large phase 3 trials in patients with ACS, AF, or cancer. However, the effect of these FXI inhibitors on catheter-induced clotting has not been explored. We previously demonstrated that inhibiting FXI reduces catheter-induced clotting in rabbits. This thesis aims to investigate the role of catheters and polyP in FXI activation and to explore the anticoagulant effects of FXI inhibitors in catheter-induced thrombosis using our established plate-based assays. We found that catheters and polyP activate clotting at the level of FXI, bypassing FXII. Both milvexian and abelacimab attenuate catheter-induced clotting. These findings suggest that FXI inhibitors could be a potential therapeutic option for catheter- and polyP-induced thrombosis without increasing bleeding risk.ThesisDoctor of Philosophy (Medical Science
Regulation and function of interphase histone H1 phosphorylation in pluripotent cell differentiation
No full textHistone H1 phosphorylation is thought to be involved in multiple cellular processes including chromatin condensation and transcriptional regulation. Recent studies revealed changes in the expression and genomic distributions of H1 variants during cell differentiation which appear to contribute to phenotypic differences between cell types, but the functional significance of phosphorylation at specific sites in individual H1 variants and their dynamic regulation in this process has not been investigated. Here we show that the global levels of phosphorylation of H1.5-Ser18 (pS18-H1.5), H1.2/H1.5-Ser173 (pS173-H1.2/5) and H1.4-Ser187 (pS187-H1.4) are regulated differentially during pluripotent cell differentiation. Enrichment of pS187-H1.4, but not pS18-H1.5, near the transcription start sites (TSSs) of pluripotency factor genes is diminished after differentiation. Selective inhibition of CDK7 and CDK9, or siRNA depletion of CDK9 rapidly diminishes both the global levels and the enrichment of pS187-H1.4 at housekeeping genes. Moreover, inhibiting transcription with actinomycin D induces the accumulation of pS187-H1.4 at promoters and gene bodies. Notably, the levels of pS187-H1.4 enrichment after actinomycin D treatment or cell differentiation reflect the extent of CDK9 recruitment at the same loci. Remarkably, the global levels of H1.5-S18 and H1.2/H1.5-S173 phosphorylation are not affected by these transcription inhibitor treatments, and selective inhibition of CDK2 does not affect global phosphorylation of H1.4-S187 or H1.5-S18. Although Erk phosphorylates S187-H1.4 in vitro, our data with Erk inhibitor treatments and EGF stimulation suggest that Erk does not phosphorylate S187-H1.4 in vivo. Studies of cells expressing H1.4 mutants that mimic constitutive dephosphorylation and phosphorylation at one or two interphase sites reveal that interphase phosphorylation of H1.4 affects transcription in a gene-specific manner. Taken together, our data provide strong evidence that H1 variant phosphorylations are dynamically regulated in a site-specific and gene-specific fashion during pluripotent cell differentiation, and that the enrichment of pS187-H1.4 at genes is positively related to their transcription. H1.4-S187 is likely to be a direct target of CDK9 during interphase in vivo while other H1 variant phosphorylations appear to be mediated by distinct kinases.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-05-01The student, Ruiqi Liao, accepted the attached license on 2017-04-17 at 17:05.The student, Ruiqi Liao, submitted this Dissertation for approval on 2017-04-17 at 17:20.This Dissertation was approved for publication on 2017-04-18 at 12:54.DSpace SAF Submission Ingestion Package generated from Vireo submission #10822 on 2017-08-10 at 15:05:51Made available in DSpace on 2017-08-10T20:33:00Z (GMT). No. of bitstreams: 3
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Previous issue date: 2017-04-18Embargo set by: Colleen Fallaw for item 102773
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Learning and representing attributed graphs
No full textUniversity of Technology Sydney. Faculty of Engineering and Information Technology.Information graphs are ubiquitous in many areas, such as medicine, social media and academic engines, and each node in the graph comes with various attributes. For example, in a academic citation graph, we can take each paper a node, then the author(s) and title of each paper can be extracted as the attributes of the node. Moreover, papers, authors as well as venues can be taken as different sources of nodes in one information graph. By doing so, we have got a heterogeneous information graph with more than one sources of nodes, attributes and links.
To implement these applications, such as identifying protein residues and social media marketing, graph representation of homogeneous information graphs has been widely researched and employed. This research, aims to embed and represent homogeneous nodes with low-dimensional and unified vectors, while preserving the contextual information between nodes, and, as a result, classical machine learning methods can be directly applied.
However, existing graph embedding algorithms are facing five major challenges: 1.the graph representation learning and node classification in graphs are separated into two steps, which may result in sub-optimal results because the node representation may not fit the classification model well; 2. existing ones are mostly shallow methods that can only capture the linear and simple relationships in the data; 3. Ignoring the data distribution of the latent codes from the graphs, which often results in inferior embedding in real-world graph data; 4. unable to handle the heterogeneous and multi-relational information graph which is the major form that graph data existed in the real-world; and 5. unable to effectively discover functional groups and understand the roles of detected groups.
To face the aforementioned challenges, the main research objective of the thesis is to study that how to more effectively embed the nodes of a graph into a compact space for the tasks which are most related to the real-world applications.
The main research objective has been studied from four coherently linked perspectives: (1) How to unify the traditional two-step embedding work-flow into one smooth embedding procedure to avoid the inconsistency between the embedding architecture and classifier; (2) How to learn a universal embedding for all sources of nodes in a graph, so one single embedding can be used to represent the entire heterogeneous information graph; (3) How to smoothly regularize the embedding with a certain distribution during the learning procedure for a more robust embedding; (4) How to automatically generate a human-understandable explanation of each cluster of nodes in the graph and applied the algorithm in the real business world.
Specifically, this thesis aims to tackle aforementioned challenges by conducting studies of graph ladder network to unifies both representation and classifier model learning into one framework; developing universal graph representation to represent different types of nodes in heterogeneous information graph in a continuous and common vector space; introducing generative adversarial scheme into graph domain to encode the topological structure and node content in a graph to a compact representation, on which a decoder is trained to reconstruct the graph structure under an adversarial training scheme and carrying out co-clustering on enterprise information graph for functional group discovery and understanding. All works in this thesis are validated with related tasks like graph classification, graph clustering, graph visualization and link prediction respectively
Design of 3D Laser Scanner and Calibration Objects
No full text3D scanning is commonly used for rapid prototyping, which is a process of converting real world objects into digital models. Most commercial laser scanners in the market are expensive and the scanning process is relatively slow. This research explores the design of an inexpensive 3D laser scanner with medium accuracy for daily use. The purpose of this research is to evaluate the technical performance capability of a DIY laser scanner and compare it to the capability of a commercial scanner. As part of this analysis, a set of standard calibration objects will be developed for a range of volume sizes. The first stage of this research is to construct a portable, inexpensive 3D laser scanner. The scanning system consists of a camera, four line lasers and a turntable. A stepper motor actuates the turntable and an Arduino is utilized in this design as a controller. The Arduino communicates with an open source scanning software program via COM ports. The scanning software is used to perform the image processing and save the scanned image as files which can be utilized for 3D printing by a standard fused deposition modeling device. The second phase of this research aims to improve the accuracy of the scanner by modifying the design. Also, tolerance analysis is also conducted during the design procedure. Finally, in order to evaluate and compare the scanning performance of different scanners, several calibration objects were designed. The result of this study can provide a simple standard method for evaluating the scanning capability of a 3D scanning system, as well as an improved design for an inexpensive 3D laser scanner.College of Engineering, The Ohio State University.No embargoAcademic Major: Mechanical Engineerin
Assessing IP Weight Metrics for Cloud Intrusion Detection using Machine Learning Techniques
No full textDespite the growing popularity of cloud computing, security is still an important concern of cloud customers and potential adopters. Cloud computing is prone to the same attack vectors as traditional networks, in addition to new attack vectors that are specific to cloud platforms. Intrusion Detection Systems (IDS) deployed in the cloud must take into account the specificity of the underlying threat landscape as well as the architectural and operational constraints of cloud platforms. In this project, an IDS that utilizes IP weight metrics for feature selection is implemented. Additionally, this system is tested with different supervised classification models and evaluated on a cloud intrusion dataset. In comparison with the results under conventional network environment, we conclude that the performance of IDS against cloud intrusions is promising, however, other developments such as unsupervised intrusion detection techniques and extra data preprocessing stages should be researched for the best practice of the system.Graduat
Краткое Видео Как Средство Формирования Национальной Идентичности В Современном Китае (Short Video as a Tool of Forming National Identity in Contemporary China)
No full textSaat ini, media sosial memainkan peran yang sangat penting dalam transmisi dan pertukaran data di seluruh dunia, tidak terkecuali China. Platform video pendek telah mendapatkan popularitas khusus di antara media sosial dalam beberapa tahun terakhir. Berkaitan dengan hal tersebut, kami telah melakukan studi yang memberikan wawasan tentang bagaimana platform video pendek Tiongkok dapat menjadi alat untuk membangun identitas nasional di era media sosial di Tiongkok. Sebagai hasil analisis, diketahui bahwa video pendek memainkan peran penting dalam membentuk rasa identitas nasional di Tiongkok modern. Video pendek sebagai alat untuk pembentukan identitas nasional dipertimbangkan pada contoh layanan Douyin. Di Douyin, pembentukan identitas nasional tercermin dalam video dengan tagar "Energi Positif". Halaman Energi Positif menampilkan video untuk menggambarkan kekayaan, kemakmuran, dan kekuatan nasional China. "Energi Positif" berfokus pada isu-isu sosial dan moral, memperkuat tanggung jawab bersama untuk menangani isu-isu tersebut berbarengan dengan negara, mendorong perilaku moral yang aktif, menjadikannya ekspresi yang berguna untuk pembentukan identitas nasional. Juga dicatat bahwa video pendek Douyin memvisualisasikan dan menyuarakan keterikatan simbolis dengan bangsa, yang berkontribusi pada keterikatan emosional yang lebih besar pada bangsa dan rasa identitas nasional
Интеграция и инновации основных национальных СМИ в Китае
No full textThe article discusses the features of integration and implementation of innovations in the main national media of the People's Republic of China (using the example of the news program "Anchor Talking Lianbo", which is broadcast on the Weibo platform). The rapidity of such development is noted, the main emphasis in the article is placed on the transformation of media resources, as well as on the implementation of new approaches in the activities of the media, allowing to attract all target segments.В статье рассмотрены особенности интеграции и внедрения инноваций в основные национальные СМИ Китайской Народной Республики (на примере новостной передачи «Anchor Talking Lianbo», которую транслируют на платформе Weibo). Отмечается стремительность такого развития, основной упор сделан на трансформации медийных ресурсов, а также на реализации новых подходов в деятельности средств массовой информации, позволяющих привлекать все целевые сегменты
A Variable Stiffness Robotic Arm Design Using Linear Actuated Compliant Parallel Guided Mechanism.
No full textMagnetfältsförstärkning för 1,5 T MRI med hjälp av en avancerad cylindrisk resonator med stor bländare
No full textMagnetic resonance imaging (MRI) is a non-invasive imaging technique widely used in medical diagnostics to provide high-resolution human body images. The image resolution depends on the signal-to-noise ratio (SNR), which is proportional to the square of the radio frequency magnetic field |B1|. Many studies have proposed using additional passive devices inside the birdcage of MRI to strengthen |B1|, such as using high permittivity layers, local resonators, etc. Among these studies, a cylindrical resonator with a radius of 48 mm as a local resonator has already proven effective for wrist imaging. However, when the resonator aperture is enlarged to accommodate larger body parts (e.g., a hand), |B1| in its central region decays significantly, and the radial field becomes non-uniform. To address this shortcoming, a circularly slotted endcap (CSE) and an interval field suppressor (IFS) that can be integrated on a wide-aperture cylindrical resonator are proposed. The wide aperture resonator with these two structural add-ons can sufficiently enhance |B1| and its homogeneity. Full-wave CST simulations of two case studies are carried out for resonators with inner radii of 104 mm and 130 mm, over twice the original design for the wrist. With CSE and IFS, the central |B1| increases by 15.5% and 25.6% relative to the bare 104 mm and 130 mm resonator, respectively, while maintaining radial field inhomogeneity below 5%. Compared with a standalone birdcage coil, the integrated assemblies (cylindrical resonator + CSE + IFS) can achieve a 141.9% and 99.4% increase in central |B1| for the two radii cases. These two case studies show that the CSE and IFS provide a general, scalable way of enhancing |B1| and uniformity in large-aperture cylindrical resonators, extending their use to clinical imaging of other larger body parts than the wrist, such as hands. The design is compatible with standard hardware and can be fabricated with low-cost materials, laying the groundwork for future in-vivo studies and clinical translation.Magnetresonanstomografi (MRI) är en icke-invasiv avbildningsteknik som används i stor utsträckning inom medicinsk diagnostik för att generera högupplösta bilder av människokroppen. Bildupplösningen beror på signal-brus-förhållandet (SNR), vilket är proportionellt mot kvadraten på det sändande radiofrekventa magnetfältet |B1|. Flera studier har föreslagit att man placerar passiva strukturer inne i MRI:ns birdcage-spole för att förstärka |B1|, såsom högpermittivitetsmaterial, lokala resonatorer osv. Bland dessa har en cylindrisk resonator med en radie på 48 mm visat sig vara effektiv för handledsavbildning. När resonatorns öppning utökas för att rymma större kroppsdelar (t.ex. en hand) minskar dock |B1| avsevärt i det centrala området, och fältfördelningen blir radiellt icke-uniform. För att åtgärda denna brist föreslås en cirkulärt slitsad ändplatta (CSE) samt en fältförsvagare (IFS) som kan integreras med en cylindrisk resonator med stor öppning. Med dessa två tillägg kan resonatorn avsevärt förstärka |B1| samt förbättra dess homogenitet. Fullvågssimuleringar i CST har utförts för två resonatorer med innerradier på 104 mm respektive 130 mm – mer än dubbelt så stora som ursprungsdesignen för handleden. Med CSE och IFS ökar det centrala |B1| med 15,5% respektive 25,6% jämfört med respektive naken resonator, samtidigt som radiell fältinhomogenitet hålls under 5%. Jämfört med en ensam birdcage-spole uppnås en ökning av centralt |B1| med 141,9% respektive 99,4% i de två fallen med CSE+IFS. Dessa två fallstudier visar att CSE och IFS erbjuder ett generellt och skalbart sätt att förbättra |B1|-fältet och dess jämnhet i cylindriska resonatorer med stor öppning. Detta gör att tekniken kan användas för klinisk avbildning av andra större kroppsdelar än handleden, såsom händer. Konstruktionen är kompatibel med standardhårdvara och kan tillverkas med billiga material, vilket lägger grunden för framtida in-vivo-studier och klinisk tillämpning
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