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Search Results: 1 - 10 of 101 matches for " Marinee Chuah "
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Repression of Cardiac Hypertrophy by KLF15: Underlying Mechanisms and Therapeutic Implications
Joost J. Leenders, Wino J. Wijnen, Ingeborg van der Made, Monika Hiller, Melissa Swinnen, Thierry Vandendriessche, Marinee Chuah, Yigal M. Pinto, Esther E. Creemers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036754
Abstract: The Kruppel-like factor (KLF) family of transcription factors regulates diverse cell biological processes including proliferation, differentiation, survival and growth. Previous studies have shown that KLF15 inhibits cardiac hypertrophy by repressing the activity of pivotal cardiac transcription factors such as GATA4, MEF2 and myocardin. We set out this study to characterize the interaction of KLF15 with putative other transcription factors. We first show that KLF15 interacts with myocardin-related transcription factors (MRTFs) and strongly represses the transcriptional activity of MRTF-A and MRTF-B. Second, we identified a region within the C-terminal zinc fingers of KLF15 that contains the nuclear localization signal. Third, we investigated whether overexpression of KLF15 in the heart would have therapeutic potential. Using recombinant adeno-associated viruses (rAAV) we have overexpressed KLF15 specifically in the mouse heart and provide the first evidence that elevation of cardiac KLF15 levels prevents the development of cardiac hypertrophy in a model of Angiotensin II induced hypertrophy.
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt,Avedis Kazanjian,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P. Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F. Shroyer,Bassem A. Hassan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt equal contributor,Avedis Kazanjian equal contributor,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F Shroyer ,Bassem A Hassan
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
A format for databasing and comparison of AFLP fingerprint profiles
Yan Hong, Aaron Chuah
BMC Bioinformatics , 2003, DOI: 10.1186/1471-2105-4-7
Abstract: A scheme is described to represent a DNA fingerprint profile with a nucleotide sequence-like format in which the information line contains the minimal necessary details to interpret an AFLP DNA fingerprint profile. They include technique used, information on restriction enzymes, primer combination, biological source for DNA materials, fragment sizing and annotation. The bodylines contain information on size and relative intensity of DNA fragments by a string of defined alphabets or symbols. Algorithms for normalizing raw data, binning of fragments and comparing AFLP DNA fingerprint profiles are described. Firstly, the peak heights are normalized against their average and then represented by five symbols according to their relative intensities. Secondly, a binning algorithm based loosely on common springs and rubber bands is applied, which positions sequence fragments into their best possible integer approximations. A BLAST-like reward-penalty concept is used to compare AFLP fingerprint profiles by matching peaks using two metrics: score and percentage of similarity. A software package was developed based on our scheme and proposed algorithms. Example of use this software is given in evaluating novelty of a new tropical orchid cultivar by comparing its AFLP fingerprint profile against those of related commercial cultivars in a database.AFLP DNA fingerprint profiles can be databased and compared effectively with software developed based on our scheme and algorithms. It will facilitate wider use of this DNA fingerprinting technique in areas such as forensic study, intellectual property protection for biological materials and biodiversity management. Moreover, the same concepts can be applied to databasing and comparing DNA fingerprint profiles obtained with other DNA fingerprint techniques.DNA markers reflect difference in the DNA sequences of chromosomes derived from different progenitors. They arise as a result of mutations as well as rearrangements in the DNA interv
The Cultural and Social Interaction between Chinese Muslim Minorities and Chinese Non-Muslim Majority in China: A Sociological Analysis
Osman Abdullah Chuah
Asian Social Science , 2012, DOI: 10.5539/ass.v8n15p267
Abstract: The paper is a research on the interaction between Chinese Muslim minority, the Hui with the non-Muslim majority, the Han in China. The findings prove that the Hui in China remain a marginalized group with little influence on political, economical, cultural and social affairs. It is also confirmed that for the Hui people, Islam is practised as a comprehensive way of life unlike the Chinese non-Muslims. In China, the non-Muslim majority, the Han recognize the Hui people only as a minority ethnic group. There are three kinds of relationship between the Muslim Hui and the non-Muslim Han. First, there is peaceful co-existence between the non-Muslim Han and Muslim Hui, the latter resisting the great force of assimilation and acculturation of non-Muslim ways. Second, there is intensification and persecution of the Hui by the Han. Third, the Hui cannot take the pressure of intensified prejudice, persecution and discrimination and so they revolt against the Han. These three kinds of relationship continue to exist in China depending on the delicate and complex situation between the non-Muslim Han and the Muslim Hui in China.
Kaehler structures on Kc/(P,P)
Meng-Kiat Chuah
Mathematics , 1996,
Abstract: Let K be a compact semi-simple Lie group. We classify K-invariant Kaehler structures on the space Kc/(P,P), where Kc is the complexification of K, P is a parabolic subgroup of Kc, and (P,P) the commutator subgroup. For each Kaehler structure, we study its moment map and associated pre-quantum line bundle for geometric quantization. Some holomorphic sections of the line bundle form a unitary K-representation space, and we study the multiplicity of its irreducible subrepresentations.
Improved Multiple-Scenario Radio Network Dimensioning for WCDMA  [PDF]
Thiaw Seng Ng, Teong Chee Chuah, Yifei Tan
Int'l J. of Communications, Network and System Sciences (IJCNS) , 2012, DOI: 10.4236/ijcns.2012.51003
Abstract: In wideband code division multiple access (WCDMA) cellular systems, the coverage radius of a cell depends on its current capacity level. As a result, existing WCDMA radio network dimensioning approaches require that coverage and capacity planning be carried out jointly in an iterative manner in order to obtain the minimum site count needed while fulfilling both coverage and capacity requirements. This requires relatively long computational time, particularly when there are many scenarios or what-if cases to be considered. To overcome this problem, we propose an alternative radio network dimensioning approach where coverage planning and capacity planning can be carried out separately to reduce computational time. Besides, a portion of the values calculated in the initial iteration is preserved in a lookup graph, allowing future what-if analysis to be accomplished rapidly. Simulation results show that, unlike the existing approach, the planning and what-if analysis times of the proposed dimensioning approach are independent of the number of sce-narios considered. Lastly, we present a few case studies and show that the proposed dimensioning method can give the same prediction accuracy as the existing method.
Improved Radio Network Dimensioning for Real-Time Polling Service on IEEE 802.16 Wireless Networks with QoS Consideration  [PDF]
Thiaw Seng Ng, Teong Chee Chuah, Yi Fei Tan
Int'l J. of Communications, Network and System Sciences (IJCNS) , 2012, DOI: 10.4236/ijcns.2012.53024
Abstract: Recently, applications of real-time polling service (rtPS) in IEEE 802.16 wireless networks have gained considerable popularity. These applications generate large amounts of real time traffic in the network and thus maintaining the quality of service (QoS) such as packet delay requirement in rtPS dominant networks is critical. Existing dimensioning methodology does not consider QoS parameters of rtPS in network dimensioning. Moreover, exhaustive and time-consuming simulations are required to evaluate the performance and QoS of rtPS. To overcome this problem, we propose an improved radio network dimensioning framework which considers QoS parameters of rtPS in network dimensioning. In this framework, an analytical model is developed to evaluate the capacity and performance of rtPS in IEEE 802.16 wireless networks. The proposed framework provides a fast and accurate means of finding the trade-off between system load and packet delay, thus providing network operators with an analytical tool that jointly considers coverage, capacity and QoS requirements for obtaining the minimum number of sites required. The accuracy of the proposed model is validated through simulations.
Design of Pixellated CMOS Photon Detector for Secondary Electron Detection in the Scanning Electron Microscope
Joon Huang Chuah,David Holburn
Advances in OptoElectronics , 2011, DOI: 10.1155/2011/648487
Abstract: This paper presents a novel method of detecting secondary electrons generated in the scanning electron microscope (SEM). The method suggests that the photomultiplier tube (PMT), traditionally used in the Everhart-Thornley (ET) detector, is to be replaced with a configurable multipixel solid-state photon detector offering the advantages of smaller dimension, lower supply voltage and power requirements, and potentially cheaper product cost. The design of the proposed detector has been implemented using a standard 0.35?μm CMOS technology with optical enhancement. This microchip comprises main circuit constituents of an array of photodiodes connecting to respective noise-optimised transimpedance amplifiers (TIAs), a selector-combiner (SC) circuit, and a postamplifier (PA). The design possesses the capability of detecting photons with low input optical power in the range of 1?nW with 100?μm × 100?μm?sized photodiodes and achieves a total amplification of 180?dBΩ at the output. 1. Introduction The Everhart-Thornley (ET) detector has been widely used as the secondary electron detector for the scanning electron microscope (SEM) for the past half a century [1]. The detector consists mainly of collector, scintillator, light pipe, photomultiplier tube (PMT), and preamplifier. Being a vital component of the ET detector, PMT is responsible for sensing the arrival of photons, converting them to electrons, and multiplying the number of electrons which essentially produce an amplified output current. Its dominance of use is due chiefly to its ability to provide an excellent sensitivity solution. The rapid advancement of semiconductor technologies in recent years has manifested in many applications in various fields. Solid-state method essentially allows the integration of large operating components into a small microchip. Complementary metal-oxide-semiconductor (CMOS) processes, which are silicon based, have become the most popular among all technologies thanks to its ability to provide low-cost solutions and highly integrated design. Certain CMOS processes do attract special attention owing to their ability to include both optical devices and electrical circuits into a monolithic microchip. This form of integration is very popular in the optical communications world, both wired and wireless, in the past decade [2–5]. Apart from communications, it also finds a number of implementations in optical storage systems [6]. In the optical sensory sectors, numerous applications such as camera sensory devices, optical microsensors particularly used in medical monitoring, and
Targeted treatment of imatinib-resistant chronic myeloid leukemia: Focus on dasatinib
Charles Chuah, Junia V Melo
OncoTargets and Therapy , 2009, DOI: http://dx.doi.org/10.2147/OTT.S3971
Abstract: rgeted treatment of imatinib-resistant chronic myeloid leukemia: Focus on dasatinib Review (5067) Total Article Views Authors: Charles Chuah, Junia V Melo Published Date April 2009 Volume 2009:2 Pages 83 - 94 DOI: http://dx.doi.org/10.2147/OTT.S3971 Charles Chuah1, Junia V Melo2 1Singapore General Hospital and Duke-NUS Graduate Medical School, Singapore; 2Institute of Medical and Veterinary Science, South Australia, Australia Abstract: The efficacy of imatinib in chronic myeloid leukemia has been remarkable, but the development of resistance and the persistence of minimal residual disease have dampened the initial enthusiasm for this much heralded ‘magic bullet’. Much progress has been made in elucidating the mechanisms which underlie imatinib resistance. The most common cause of such drug resistance is the selection of leukemic clones with point mutations in the Abl kinase domain leading to amino acid substitutions which prevent the appropriate binding of the drug. Other mechanisms include genomic amplification of BCR-ABL and modulation of drug efflux or influx transporters. Dasatinib is a multi-target kinase inhibitor which has increased potency and is able to inhibit most Bcr-Abl mutant cell lines. Clinical trials of dasatinib in imatinib-resistant and -intolerant chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoid leukemia have shown that it is effective and well tolerated. In this review, we will discuss the pre-clinical development of dasatinib, the clinical trial data demonstrating its efficacy and tolerability and highlight certain aspects of its toxicity profile and mechanisms of resistance.
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