289 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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Text-to-Song: Towards Controllable Music Generation Incorporating Vocals and Accompaniment
No full textA song is a combination of singing voice and accompaniment. However, existing
works focus on singing voice synthesis and music generation independently.
Little attention was paid to explore song synthesis. In this work, we propose a
novel task called text-to-song synthesis which incorporating both vocals and
accompaniments generation. We develop Melodist, a two-stage text-to-song method
that consists of singing voice synthesis (SVS) and vocal-to-accompaniment (V2A)
synthesis. Melodist leverages tri-tower contrastive pretraining to learn more
effective text representation for controllable V2A synthesis. A Chinese song
dataset mined from a music website is built up to alleviate data scarcity for
our research. The evaluation results on our dataset demonstrate that Melodist
can synthesize songs with comparable quality and style consistency. Audio
samples can be found in https://text2songMelodist.github.io/Sample/.Comment: ACL 2024 Mai
Recommended from our members
Effective Learning of Descriptive and Generator Models and Learning Representations for Grid Cells and V1 Cells
No full textIn recent decades, deep learning has achieved tremendous successes in supervised learning; however, unsupervised learning and representation learning, i.e., learning the hidden structure of the data without requiring expensive and time-consuming human annotation, remains a fundamental challenge, which probably underlies the gap between current artificial intelligence and the intelligence of a biological brain. In this thesis, we propose novel solutions to the problems in this area. Specifically, we work on deep generative modeling, an important approach of unsupervised learning, and representation learning inspired by structures in the brain. 1. We propose efficient algorithms for learning descriptive models, which are also known as energy-based models (EBMs). Despite an appealing class of generative models with a number of desirable properties, the learning of descriptive models on high-dimensional space remains challenging, which involves computationally expensive Markov chain Monte Carlo (MCMC). To tackle this problem, we propose a multi-grid modeling and sampling method, which learns descriptive models at multiple scales or resolutions and the MCMC sampling follows a coarse-to-fine scheme. This approach enables efficient learning and sampling of descriptive models from large-scale image datasets with small-budget MCMC. Later on, we extend this method to an improved version named diffusion recovery likelihood, where a sequence of descriptive models are proposed and learned on increasingly noisy versions of a dataset. Each descriptive model is trained by sampling from the conditional probability of the data at a certain noise level given their noisy versions at a higher noise level, which further releases the burden of MCMC.
2. We develop dynamic and motion-based generator models which learn semantically meaningful vector representations for spatial-temporal processes such as dynamic textures and action sequences in video data. The models are capable of learning disentangled representations of appearance, trackable motion and intrackable motion in spatial-temporal processes in a fully unsupervised manner. We also propose an efficient learning algorithm named alternating back-propagation through time, which learns the proposed models using online MCMC inference without resorting to auxiliary networks. 3. We propose hybrid generative models that integrate the advantages of different classes of generative models. Specifically, we propose a training algorithm flow contrastive estimation to jointly estimate a descriptive model and a flow-based model, in which the two models are iteratively updated based on a shared adversarial value function. The algorithm is an extension of noise contrastive estimation (NCE) and combines the flexibility of descriptive models and the tractability of flow-based models. We also study another hybrid model where the descriptive model serves as a correction or an exponential tilting of the flow-based model. We show that this model has a particularly simple form in the space of the latent variables of the flow-based model, and MCMC sampling of the descriptive model in the latent space mixes well and traverses modes in the data space. 4. We propose an optimization-based representational model of grid cells. Grid cells exist in the mammalian medial entorhinal cortex (mEC) and are so named because individual neurons exhibit striking firing patterns that form hexagonal grids when the agent (such as a rat) navigates in a 2D open field. To understand how grid cells perform path integration, we conduct theoretical analysis of a general representational model of grid cells where the 2D self-position of the agent is represented by a higher-dimensional vector and the 2D self-motion is represented by a general transformation of the vector. We identify two conditions for the general transformation and demonstrate an important geometric property of the general transformation, i.e., local conformal embedding. We further investigate the simplest transformation, i.e., the linear transformation, and uncover its explicit algebraic and geometric structure as a matrix Lie group of rotation. The model learns significant hexagon patterns of grid cells and is capable of accurate path integration. 5. We extend the representational model of grid cells to an optimization-based representational model of V1 simple cells. V1 stands for the primary visual cortex in the mammalian brain, and V1 simple cells are highly specialized for low-level motion perception and pattern recognition. We propose a representational model of V1 simple cells which couples the following two components: (1) the vector representations of local contents of images and (2) the matrix representations of local pixel displacements caused by the relative motions between the agent and the objects in the 3D scene. The model can learn Gabor-like tunings of V1 simple cells and similar to V1 simple cells, the learned adjacent neurons have quadrature-phase relations
Measurement Analysis of Traffic Flow Uncertainty on Chinese Highway Network
No full textExtensive research has been done on traffic forecasting. However, performance of forecasting models is highly influenced by traffic uncertainty and predictability. Traffic uncertainty is important for road users and governors as well. With support of adequate real data from toll stations, we reveal laws in traffic flow uncertainty by employing dispersion coefficient. For further study, Hurst exponent and Approximate Entropy reflect temporal characteristics, indicating long-term randomness and short-term complexity respectively. These measurements all suggest that traffic flow uncertainty drops with the increase of time interval. Our study provides effective measuring methods of uncertainty and theoretical evidence for 15 minutes time horizon in short-term traffic prediction. Daily periodicity exists that highway traffic flow at night is more uncertain than in day time, and off-peak hour flows are more uncertain than peak hour flows. Finally, initial investigation into traffic predictability exhibits acme at 7 a.m. in our case.Automation & Control SystemsComputer Science, Artificial IntelligenceEngineering, Electrical & ElectronicTransportation Science & TechnologyEICPCI-S(ISTP)
Valued fields: p-adic numbers as a case study
No full textIn this thesis, we first build the idea of field valuation and look into some
of its examples, followed by the idea of general absolute value, as they are
closely related. Then, an absolute value induces a metric, and we can talk
about completions of fields with respect to the induced metric. In particular,
we examine in detail the field of p-adic numbers as a great example. Finally,
we return to general valued fields, and extract this process entirely onto
the valuation level, bypassing absolute value and induced metric. Most
importantly, we want to apply Hensel’s lemma on general valued fields, and
in the end we shall see when it is possible.Bachelor of Science in Mathematical Science
An Integrated Full-bridge Class-DE Ultrasound Transducer Driver for HIFU Applications
No full textThis thesis present a CMOS integrated transducer driver for high intensity focused ultrasound
(HIFU) applications. Because this driver will be used in a magnetic resonance imaging (MRI)
environment, no magnetic components such as inductors and transformers have been used in this
design. The transducer is directly connected to the driver without a matching network. The output
stage of this driver is a full-bridge Class DE RF amplifer which is able to deliver more power than
the previous design that has a half-bridge Class DE amplifer.
The driver was also designed to be used in a transducer array. A digital control unit was
integrated with the power amplifer that allows to program the drivers phase shift and duty ratio.
A strategy to drive a ultrasound transducer array using the designed driver is also presented in this
thesis.
This design was implemented using the AMS H35B4 CMOS technology using the Cadence suite
of design tools and occupies a die area of 2mm by 1.5mm with 20 input and output pads. Simulation
and initial experimental results are presented in this work. The proposed integrated CMOS driver
has an efficiency of 89.4% with 3.60 W of output power. Results are little bit different for each
transducer
Apeldoorn leisure paradise
No full textThe graduation project attempts to discuss the possible approaches for transferring the Centraal Beheer into a leisure and recreation center.Centraal BeheerArchitecture, Urbanism and Building Science
Oreta loochooana subsp. timutia Watson 1967
No full textOreta loochooana timutia Watson, 1967 Figs. 16, 67, 137, 164 Oreta loochooana timutia, Watson, 1967, Bull. Br. Mus. nat. Hist. (Ent.), 19 (3): 168, figs 10–11. Holotype 3, China: Hunan, Hoeng-shan (ZFMK). Oreta trianga Chu & Wang sensu Chu & Wang, 1987, Acta Ent. Sin., 30 (3): 300. (part) Oreta pulchripes Butler sensu Chu & Wang, 1987, Acta Ent. Sin., 30 (3): 295. Material examined. CHINA, Hunan (ZFMK): Hoeng-shan, 900 m, 28.IV. 1933, coll. Höne, 13 (Holotype). Zhejiang (IZCAS): Mokan Shan, 16.V. 1936, coll. O. Piel, 13. Hubei (IZCAS): Badong, Tiechanghuang Linchang, 19.V. 1989, 13; Xingshan, Longmenhe, 670–1350 m, 19.VI. 14.–VIII. 1993, coll. Huang Runzhi et al., 531 Ƥ; same locality, 1300 m, 7– 9.V., 9–12.IX. 1994, coll. Song Shimei, 331 Ƥ; Xingshan, Xiaohekou, 700 m, 11.V. 1994, coll. Li Wenzhu, 23; Zigui, Jiulingtou, 100 m, 13.VI. 1993, coll. Yao Jian, 131 Ƥ; same locality, 110 m, 5–7.IX. 1994, coll. Song Shimei, 131 Ƥ; Xuan’en, Changtan, 650 m, 25.V. 1989, coll. Li Wei, 13; Lichuan, Xingdoushan, 800 m, 23.VII. 1989, coll. Li Wei, 13; Shennongjia, Muyu, 22.VII. 1998, coll. Zhou Haisheng, 1 Ƥ; Shennongjia, Dongxi, 600 m, 3.VIII. 1998, coll. Ye Chanjuan, 13; no data, 11.IX. 1980, 13. Jiangxi (IZCAS): Kuling, 14.IX., 5–17.VIII. 1934, coll. O. Piel, 43; Doushui, 5.VII. 1975, coll. Song Shimei, 1 Ƥ (Paratype of O. trianga). Hunan (IZCAS): Dong’an, 20.V. 1954, 1Ƥ; Zhangjiajie, 8–15.X. 1988, coll. Fang Chenglai, 333 Ƥ; Guidong, Siduxiang, 774 m, 7–12.VII. 2008, coll. Chen Fuqiang, 13. Fujian (IZCAS): Guadun, 27.VIII. 1979, coll. Wang Linyao, 13; Chong’an, Tongmu, 17–21.VIII. 1979, coll. Wang Linyao, 23; Mt. Wuyi, 24.IV. 1982, coll. Zhang Baolin, 13; same locality, 12–24.V. 1983, coll. Wang Linyao, 23; Sangang, 9–26.V. 1983, coll. Wang Linyao, 53; Mt. Wuyi, Sangang, 700 m, 25–26.VII. 2006, coll. Xie Juan and Xue Dayong, 13; Mt. Wuyi, Huangxizhou, 500 m, 29.VII. 2006, coll. Xie Juan and Yang Chao, 1 Ƥ; Wuping, Liangyeshan, Xinhua, 450 m, 13–15.XI. 2008, Chen Fuqiang, 13; Wuping, Liangyeshan, Kongxia, 481–627 m, 17–19.XI. 2008, coll. Chen Fuqiang, 33. Guangxi (IZCAS): Pingxiang, 230 m, 8–12.VI. 1975, coll. Zhang Baolin, 23. Sichuan (IZCAS): Dukou, 23.VIII. 1980, coll. Zhang Baolin, 13; Nanping, Jiuzhaigou, 2300 m, 7.IX. 1983, coll. Wang Ruiqi, 1 Ƥ; Mt. Emei, Qingyinge, 800–1000 m, 22–26.IV, 20.VI. 1957, coll. Zhu Fuxing et al., 53; Qingchengshan, 4.VI. 1979, coll. Shang Jinwen, 13. Chongqing (IZCAS): Wanxian, Wang’erbao, 1200 m, 12.VIII. 1993, coll. Song Shimei, 43; same locality, 1200 m, 27–28.V. 1994, coll. Li Wenzhu, 331 Ƥ; Fengdu, 610 m, 5.X. 1994, coll. Song Shimei, 33. Yunnan (IZCAS): Deqin, Baimangxueshan, 3700 m, 27.VII. 1981, coll. Wang Shuyong, 13; Lijiang, Yulongshan, 2950 m, 30.VII– 22.VIII. 1962, coll. Song Shimei, 43; Lijiang, Baishui, 2980 m, 18.VII. 1979, 13; Lijiang, Yufengsi, 2700 m, VII. 1979, 13; Lijiang, Yuhu, 2700 m, 22.VII. 1984, coll. Liu Dajun, 13; Shalin, Huacaopo, 2700 m, 26.VIII. 2001, coll. Cao Xiuwen, 1 Ƥ; Jinping, Hetouzhai, 1700 m, 15.V. 1956, coll. Huang Keren, 13. Diagnosis. See under nominate subspecies. Distribution. China (Zhejiang, Hubei, Jiangxi, Hunan, Fujian, Guangdong, Guangxi, Sichuan, Chongqing, Yunnan). Remarks. All the material collected from Lijiang and Deqin, Yunnan, and published as O. pulchripes in Chu & Wang (1987, 1991), was misidentified, and is referred by us to O. loochooana. One female paratype of O. trianga Chu & Wang, 1987, from Doushui, Jiangxi, was found to be identical to O. loochooana timutia.Published as part of Song, Wenhui, Xue, Dayong & Han, Hongxiang, 2012, Revision of Chinese Oretinae (Lepidoptera, Drepanidae), pp. 1-36 in Zootaxa 3445 on pages 9-12, DOI: 10.5281/zenodo.21298
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