36,101 research outputs found
Transcription factor Sox17 regulates tumor angiogenesis and the morphogenesis of tumor vasculatures
No full textTumor vasculatures generated by tumor angiogenesis are different from normal vasculatures in the morphology and function. These distinct features of tumor vessels are, in part, caused by transcriptional changes in endothelial cells during tumor angiogenesis. To understand the transcriptional regulation in endothelial cells during tumor angiogenesis, we have studied the expression and role of transcription factor Sox17 in tumor endothelial cells by using loss-of-function and gain-of-function genetic mouse models as well as a reporter mouse system. Sox17 was highly expressed in almost all tumor endothelial cells during the whole tumor angiogenesis. Its expression in tumor endothelial cells showed a strong correlation with sprouting angiogenesis. Indeed, Sox17 promoted tumor angiogenesis by sprouting. Sox17 also modulated the shape and function of tumor vessels by regulating vascular integrity in endothelium and periendothelial compartment. These vascular changes by Sox17 resulted in many changes of tumoral responses. We currently pursue to elucidate the cellular and molecular events led by Sox17 in tumor endothelial cells. Our studies demonstrate endothelial Sox17 as a key player for angiogenesis and the morphogenesis of tumor vessels by regulating gene expression
Special issue: Process safety in times of a pandemic
No full textGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Safety and Security Scienc
Distributed human computation framework for linked data co-reference resolution
No full textDistributed Human Computation (DHC) is a technique used to solve computational problems by incorporating the collaborative effort of a large number of humans. It is also a solution to AI-complete problems such as natural language processing. The Semantic Web with its root in AI is envisioned to be a decentralised world-wide information space for sharing machine-readable data with minimal integration costs. There are many research problems in the Semantic Web that are considered as AI-complete problems. An example is co-reference resolution, which involves determining whether different URIs refer to the same entity. This is considered to be a significant hurdle to overcome in the realisation of large-scale Semantic Web applications. In this paper, we propose a framework for building a DHC system on top of the Linked Data Cloud to solve various computational problems. To demonstrate the concept, we are focusing on handling the co-reference resolution in the Semantic Web when integrating distributed datasets. The traditional way to solve this problem is to design machine-learning algorithms. However, they are often computationally expensive, error-prone and do not scale. We designed a DHC system named iamResearcher, which solves the scientific publication author identity co-reference problem when integrating distributed bibliographic datasets. In our system, we aggregated 6 million bibliographic data from various publication repositories. Users can sign up to the system to audit and align their own publications, thus solving the co-reference problem in a distributed manner. The aggregated results are published to the Linked Data Cloud
Intersystem soft handover for converged DVB-H and UMTS networks
No full textDigital video broadcasting for handhelds (DVB-H) is the standard for broadcasting Internet Protocol (IP) data services to mobile portable devices. To provide interactive services for DVB-H, the Universal Mobile Telecommunications System (UMTS) can be used as a terrestrial interaction channel for the unidirectional DVB-H network. The converged DVB-H and UMTS network can be used to address the congestion problems due to the limited multimedia channel accesses of the UMTS network. In the converged network, intersystem soft handover between DVB-H and UMTS is needed for an optimum radio resource allocation, which reduces network operation cost while providing the required quality of service. This paper deals with the intersystem soft handover between DVB-H and UMTS in such a converged network. The converged network structure is presented. A novel soft handover scheme is proposed and evaluated. After considering the network operation cost, the performance tradeoff between the network quality of service and the network operation cost for the intersystem soft handover in the converged network is modeled using a stochastic tree and analyzed using a numerical simulation. The results show that the proposed algorithm is feasible and has the potential to be used for implementation in the real environment
Beyond interfaces: A usability study of Chinese journal databases
No full textA presentation at the Council on East Asian Libraries (CEAL) annual meeting in Boston, MA on March 21, 2007
Rose Galaida and the Central China Relief Records, 1946: Discovery, Investigation, and Implications
No full textThe materials in the Central China Relief Records (CCRR) collection provide a window to the experiences of Rose Galaida in Hubei. The collection consists of about 100 documents totaling over 300 pages (excluding duplicate copies) and 5 photographs.Peer reviewedPublished in the Journal of East Asian Libraries and available from the journal at: https://scholarsarchive.byu.edu/jeal/vol2011/iss153/
Breaking New Ground in East Asia Library History
No full textReview of Peter X. Zhou. Collecting Asia: East Asian Libraries in North America (2010).Published in H-Net Reviews in the Humanities and Social Sciences and available at: http://www.h-net.org/reviews/showrev.php?id=32231March 201
One step preparation of pure tau-MnAl phase with high magnetization using strip casting method
No full textFerromagnetic phase of Mn-Al exhibits great potential in the rare-earth free permanent magnetic materials due to its high magnetocrystalline anisotropy, high magnetization, high Curie temperature and low cost. In this work, the strip casting technique was applied to prepare MnAl magnetic phase. X-ray diffraction and energy dispersive X-ray analyses indicate that the as-prepared Mn54Al46 strip sample consists of pure tau-MnAl magnetic phase. It is found that the composition of Mn54Al46 is suitable to prepare tau-MnAl phase during the strip casting process. The Mn54Al46 strip sample synthesized through the strip casting exhibits a fairly high magnetization of 114 emu/g under a field of 5 T, while the coercivity of iHc = 2.8 kOe, magnetization of M-5T = 63.9 emu/g at room temperature can be obtained for Mn54Al46 powder sample. This preparation method can produce a large amount of tau-phase MnAl alloy and promote mass industrialized production. (C) 2017 Author(s)
알츠하이머병에서 뉴런 간 Tau 확산 조절 인자에 대한 연구
No full text학위논문(석사) -- 서울대학교대학원 : 자연과학대학 생명과학부, 2023. 2. 정용근.Tau 확산 (propagation)은 알츠하이머병 (AD) 환자의 뇌에서 비정상적 Tau가 세포 간 전파가 되면서 마치 prion처럼 정상적인 tau의 응집을 유도함으로써 진행된다. Tau propagation은 AD 진행에 핵심적인 단계이나 그 기전이 규명되지 않았다. 따라서 본 연구에서 tau propagation 조절 인자 발굴을 통해 기전을 설명하고자 한다. Tau propagation의 조절 인자를 찾기 위해 tau-BiFC propagation assay를 사용하여 1,800여개의 secretory protein 유전자를 screening 하였다. Tau-BiFC propagation assay는 tau propagation을 쉽게 관찰할 수 있는 cell-based assay로서 tau propagation이 일어난 세포에서만 형광이 관찰되어 tau propagation 발생 정도를 수치적으로 측정 가능하다.
스크리닝을 통해 TauSec 유전자가 tau propagation을 증가시키는 유전자로 동정되었다. TauSec은 tau propagation의 복합적인 과정 중에서 특히 uptake 단계를 촉진시키는 것으로 관찰되었다. 정제된 TauSec 단백질과 tau oligomer 처리 시 초기에 SH-SY5Y cell과 mouse primary cortical neuron에서 모두 tau uptake가 증가하는 것을 관찰할 수 있었다.
TauSec에 의한 tau uptake에는 TauSec과 TauSec receptor의 상호작용이 핵심적으로 보인다. TauSec receptor을 knock-down한 SH-SY5Y와 mouse primary cortical neuron에서 tau uptake가 현저히 감소했으며 TauSec protein을 처리해도 tau uptake를 증가시키지 못하였다. TauSec 처리 시 세포 내 TauSec receptor의 양과 modification 이 증가하는데 발현이 증가하는 것이 아니라 TauSec receptor 단백질이 축적되는 것으로 확인된다. TauSec receptor은 endolysosomal pathway에 관여하는 단백질로 알려져 있으며 장시간 TauSec 처리 시 과도한 modification이 일어나면서 정상적인 기능을 하지 못해 lysosome의 기능에 악영향을 끼치는 것으로 보인다. 따라서 TauSec은 후기에 tau clearance를 저해하는 역할까지 함으로서 tau propagation을 악화시킨다는 결론을 내릴 수 있다.
Tau propagation은 임상 치료에서 큰 의미를 가진다. Tau propagation 조절 인자를 저해하는 약물이나 항체가 개발된다면 독성을 가진 tau가 전파되기 전에 단백질을 제어할 수 있을 것이다. Tau propagation이 대뇌의 대부분 영역으로 확산되면 신경세포 사멸로 이어지기 때문에 그 단계를 방지하는 것이 치매 치료에 핵심적일 것이다. 뉴런에서 응집된 단백질의 확산은 tau 뿐만 아니라 파킨슨병(PD)에서 나타나는 alpha-synuclein에서도 보이는 현상이다. 따라서 향후에 본 연구가 PD 치료에까지 응용될 가능성도 있다.Alzheimers Disease (AD) is characterized by Amyloid beta (A) plaques and tau tangles that cause neuronal death and dementia. Tau propagation has garnered attention in AD research for its strong correlation with disease progression. Severity of neurodegeneration in AD is in line with the transneuronal spread and deposition of pathological tau, which occurs stereotypically from the entorhinal cortex to the entire cerebral cortex via the hippocampus. Tau propagation is a commonly observed phenomenon not only in AD but also in various tauopathies. Despite extensive research on tau propagation over the recent years, the mechanism underlying tau propagation remains enigmatic.
The purpose of identifying tau propagation modulators was to understand tau propagation and discover a potential therapeutic target in AD. Inhibiting interneuronal tau propagation can fundamentally transform the approach of AD therapy that is currently more focused on A-targeted therapy. I used the tau-BiFC propagation cell-based assay to screen 1,806 genes encoding secretory proteins. Here, I show that, among several genes that have demonstrated their effect on tau propagation, TauSec protein increases internalization and propagation of tau in SH-SY5Y and mouse primary cortical neurons. TauSec promotes tau internalization in neurons via interaction with its receptor, which has been reported to be involved in the assembly of V-type ATPase. Treatment of TauSec protein leads to accumulation and modification of the TauSec receptor in neuronal cells. On the other hand, knockdown of TauSec receptor in neuronal cells significantly reduces tau uptake in neuronal cells, even in the presence of TauSec. Prolonged TauSec incubation leads to increase in lysosomal pH and accumulation of intracellular tau protein, indicating dysregulation in lysosomal acidification and leading to defective tau clearance in neurons. In addition, blocking TauSec receptor with anti-TauSec receptor antibody or small molecule inhibitor (RRPPI) impairing the TauSec-TauSec receptor interaction abolishes tau uptake and tau propagation in neuronal cells. Together, the results of this research identify TauSec as a potent modulator of tau propagation, hence its value as a therapeutic target for AD and tauopathies.INTRODUCTION 1
MATERIALS AND METHODS 9
RESULTS 16
DISCUSSION 55
REFERENCES 58
국문 초록 71석
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