Displaying publications 1 - 20 of 90 in total

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  1. Fulltext Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (Trimeresurus purpureomaculatus) venom and its disintegrin (purpureomaculin)
    Tan CH, Liew JL, Navanesan S, Sim KS, Tan NH, Tan KY
    J Venom Anim Toxins Incl Trop Dis, 2020;26:e20200013.
    PMID: 32742279 DOI: 10.1590/1678-9199-JVATITD-2020-0013
    Background: The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs.

    Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.

    Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.

    Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.

  2. Fulltext Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study
    Li Z, Xia Y, Feng LN, Chen JR, Li HM, Cui J, et al.
    Lancet Oncol, 2016 Sep;17(9):1240-7.
    PMID: 27470079 DOI: 10.1016/S1470-2045(16)30148-6
    BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL.

    METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset.

    FINDINGS: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection.

    INTERPRETATION: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL.

    FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).

  3. Fulltext Computerized database management system for breast cancer patients
    Sim KS, Chong SS, Tso CP, Nia ME, Chong AK, Abbas SF
    Springerplus, 2014;3:268.
    PMID: 25045606 DOI: 10.1186/2193-1801-3-268
    Data analysis based on breast cancer risk factors such as age, race, breastfeeding, hormone replacement therapy, family history, and obesity was conducted on breast cancer patients using a new enhanced computerized database management system. My Structural Query Language (MySQL) is selected as the application for database management system to store the patient data collected from hospitals in Malaysia. An automatic calculation tool is embedded in this system to assist the data analysis. The results are plotted automatically and a user-friendly graphical user interface is developed that can control the MySQL database. Case studies show breast cancer incidence rate is highest among Malay women, followed by Chinese and Indian. The peak age for breast cancer incidence is from 50 to 59 years old. Results suggest that the chance of developing breast cancer is increased in older women, and reduced with breastfeeding practice. The weight status might affect the breast cancer risk differently. Additional studies are needed to confirm these findings.
  4. Synthesis of a DNA-targeting nickel (II) complex with testosterone thiosemicarbazone which exhibits selective cytotoxicity towards human prostate cancer cells (LNCaP)
    Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Nov 5;150:360-72.
    PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095
    Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
  5. A rhodamine based chemosensor for solvent dependent chromogenic sensing of cobalt (II) and copper (II) ions with good selectivity and sensitivity: Synthesis, filter paper test strip, DFT calculations and cytotoxicity
    Chan WC, Saad HM, Sim KS, Lee VS, Ang CW, Yeong KY, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2021 Jun 23;262:120099.
    PMID: 34198119 DOI: 10.1016/j.saa.2021.120099
    A new chemosensor 1 was synthesized by reacting rhodamine B hydrazide and 2,3,4-trihydroxybenzaldehyde, which was then characterized by spectroscopic techniques and single crystal X-ray crystallography. Sensor 1 has the ability to sense Co2+/Cu2+ ions by "naked-eye" with an apparent colour change from colourless to pink in different solvent system, MeCN and DMF respectively. Furthermore, it can selectively detect Co2+/Cu2+ among wide range of different metal ions, and it exhibits low detection limit of 4.425 × 10-8 M and 1.398 × 10-7 M respectively. Binding mode of the two complexes were determined to be 1:1 stoichiometry for Co2+ complex and 1:2 stoichiometry for Cu2+ complex through Job's plot, IR spectroscopy, mass spectrometry and 1H NMR spectroscopy. Moreover, reversibility of the sensor 1 as copper (II) ion detector was determined by using EDTA and the results showed that sensor 1 can be reused for at least 6 cycles. Other than that, a low cost chemosensor test strips were fabricated for the convenient "naked-eye" detection of Co2+ and Cu2+ in pure aqueous media. The MTT assay was conducted in order to determine the cytotoxicity of sensor 1 towards human cell lines.
  6. Local dynamic range compensation for scanning electron microscope imaging system
    Sim KS, Huang YH
    Scanning, 2015 Nov-Dec;37(6):381-8.
    PMID: 25969945 DOI: 10.1002/sca.21226
    This is the extended project by introducing the modified dynamic range histogram modification (MDRHM) and is presented in this paper. This technique is used to enhance the scanning electron microscope (SEM) imaging system. By comparing with the conventional histogram modification compensators, this technique utilizes histogram profiling by extending the dynamic range of each tile of an image to the limit of 0-255 range while retains its histogram shape. The proposed technique yields better image compensation compared to conventional methods.
  7. Improvement to the scanning electron microscope image adaptive Canny optimization colorization by pseudo-mapping
    Lo TY, Sim KS, Tso CP, Nia ME
    Scanning, 2014 Sep-Oct;36(5):530-9.
    PMID: 25139061 DOI: 10.1002/sca.21152
    An improvement to the previously proposed adaptive Canny optimization technique for scanning electron microscope image colorization is reported. The additional feature, called pseudo-mapping technique, is that the grayscale markings are temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill color information for grayscale colors in chrominance channels. This allows the presence of grayscale markings to be identified; hence optimization colorization of grayscale colors is made possible. This additional feature enhances the flexibility of scanning electron microscope image colorization by providing wider range of possible color enhancement. Furthermore, the nature of this technique also allows users to adjust the luminance intensities of selected region from the original image within certain extent.
  8. Noise variance estimation using image noise cross-correlation model on SEM images
    Sim KS, Nia ME, Tso CP
    Scanning, 2013 May-Jun;35(3):205-12.
    PMID: 22961698 DOI: 10.1002/sca.21055
    A number of techniques have been proposed during the last three decades for noise variance and signal-to-noise ratio (SNR) estimation in digital images. While some methods have shown reliability and accuracy in SNR and noise variance estimations, other methods are dependent on the nature of the images and perform well on a limited number of image types. In this article, we prove the accuracy and the efficiency of the image noise cross-correlation estimation model, vs. other existing estimators, when applied to different types of scanning electron microscope images.
  9. A contrast stretching bilateral closing top-hat Otsu threshold technique for crack detection in images
    Sim KS, Kho YY, Tso CP, Nia ME, Ting HY
    Scanning, 2013 Mar-Apr;35(2):75-87.
    PMID: 22777599 DOI: 10.1002/sca.21037
    Detection of cracks from stainless steel pipe images is done using contrast stretching technique. The technique is based on an image filter technique through mathematical morphology that can expose the cracks. The cracks are highlighted and noise removal is done efficiently while still retaining the edges. An automated crack detection system with a camera platform has been successfully implemented. We compare crack extraction in terms of quality measures with those of Otsu's threshold technique and the another technique (Iyer and Sinha, 2005). The algorithm shown is able to achieve good results and perform better than these other techniques.
  10. Reducing charging effects in scanning electron microscope images by Rayleigh contrast stretching method (RCS)
    Wan Ismail WZ, Sim KS, Tso CP, Ting HY
    Scanning, 2011 Jul-Aug;33(4):233-51.
    PMID: 21611953 DOI: 10.1002/sca.20237
    To reduce undesirable charging effects in scanning electron microscope images, Rayleigh contrast stretching is developed and employed. First, re-scaling is performed on the input image histograms with Rayleigh algorithm. Then, contrast stretching or contrast adjustment is implemented to improve the images while reducing the contrast charging artifacts. This technique has been compared to some existing histogram equalization (HE) extension techniques: recursive sub-image HE, contrast stretching dynamic HE, multipeak HE and recursive mean separate HE. Other post processing methods, such as wavelet approach, spatial filtering, and exponential contrast stretching, are compared as well. Overall, the proposed method produces better image compensation in reducing charging artifacts.
  11. Localization of burn mark under an abnormal topography on MOSFET chip surface using liquid crystal and emission microscopy tools
    Lau CK, Sim KS, Tso CP
    Scanning, 2011 Jan-Feb;33(1):13-20.
    PMID: 21462221 DOI: 10.1002/sca.20216
    This article focuses on the localization of burn mark in MOSFET and the scanning electron microscope (SEM) inspection on the defect location. When a suspect abnormal topography is shown on the die surface, further methods to pin-point the defect location is necessary. Fault localization analysis becomes important because an abnormal spot on the chip surface may and may not have a defect underneath it. The chip surface topography can change due to the catastrophic damage occurred at layers under the chip surface, but it could also be due to inconsistency during metal deposition in the wafer fabrication process. Two localization techniques, liquid crystal thermography and emission microscopy, were performed to confirm that the abnormal topography spot is the actual defect location. The tiny burn mark was surfaced by performing a surface decoration at the defect location using hot hydrochloric acid. SEM imaging, which has the high magnification and three-dimensional capabilities, was used to capture the images of the burn mark.
  12. Image noise cross-correlation for signal-to-noise ratio estimation in scanning electron microscope images
    Sim KS, Nia ME, Tso CP
    Scanning, 2011 Mar-Apr;33(2):82-93.
    PMID: 21381045 DOI: 10.1002/sca.20223
    A new and robust parameter estimation technique, named image noise cross-correlation, is proposed to predict the signal-to-noise ratio (SNR) of scanning electron microscope images. The results of SNR and variance estimation values are tested and compared with nearest neighborhood and first-order interpolation. Overall, the proposed method is best as its estimations for the noise-free peak and SNR are most consistent and accurate to within a certain acceptable degree, compared with the others.
  13. Autoregressive Wiener filtering in a scanning electron microscopy imaging system
    Sim KS, Kamel NS, Chuah HT
    Scanning, 2005 6 7;27(3):147-53.
    PMID: 15934507
    In this paper, we propose to use the autoregressive (AR)-based interpolator with Wiener filter and apply the idea to scanning electron microscope (SEM) images. The concept for combining the AR-based interpolator with Wiener filtering comes from the essential requirement of Wiener filtering for accurate and consistent estimation of the power of the noise in images prior to filter implementation. The resultant filter is called AR-Wiener filter. The proposed filter is embedded onto the frame grabber card of the scanning electron microscope (SEM) for real-time image processing. Different images are captured using SEM and used to compare the performances of the conventional Wiener and the proposed AR-Wiener technique.
  14. Robust image signal-to-noise ratio estimation using mixed Lagrange time delay estimation autoregressive model
    Sim KS, Cheng Z, Chuah HT
    Scanning, 2004 12 23;26(6):287-95.
    PMID: 15612206
    A new technique based on the statistical autoregressive (AR) model has recently been developed as a solution to signal-to-noise (SNR) estimation in scanning electron microscope (SEM) images. In the present study, we propose to cascade the Lagrange time delay (LTD) estimator with the AR model. We call this technique the mixed Lagrange time delay estimation autoregressive (MLTDEAR) model. In a few test cases involving different images, this model is found to present an optimum solution for SNR estimation problems under different noise environments. In addition, it requires only a small filter order and has no noticeable estimation bias. The performance of the proposed estimator is compared with three existing methods: simple method, first-order linear interpolator, and AR-based estimator over several images. The efficiency of the MLTDEAR estimator, being more robust with noise, is significantly greater than that of the other three methods.
  15. Image signal-to-noise ratio and noise variance estimation using autoregressive model
    Kamel NS, Sim KS
    Scanning, 2004 12 23;26(6):277-81.
    PMID: 15612204
    During the last three decades, several techniques have been proposed for signal-to-noise ratio (SNR) and noise variance estimation in images, with different degrees of success. Recently, a novel technique based on the statistical autoregressive model (AR) was developed and proposed as a solution to SNR estimation in scanning electron microscope (SEM) image. In this paper, the efficiency of the developed technique with different imaging systems is proven and presented as an optimum solution to image noise variance and SNR estimation problems. Simulation results are carried out with images like Lena, remote sensing, and SEM. The two image parameters, SNR and noise variance, are estimated using different techniques and are compared with the AR-based estimator.
  16. Image signal-to-noise ratio estimation using the autoregressive model
    Sim KS, Kamel NS
    Scanning, 2004 7 31;26(3):135-9.
    PMID: 15283250
    In the last two decades, a variety of techniques for signal-to-noise ratio (SNR) estimation in scanning electron microscope (SEM) images have been proposed. However, these techniques can be divided into two groups: first, SNR estimators of good accuracy, but based on impractical assumptions; second, estimators based on realistic assumptions but of poor accuracy. In this paper we propose the implementation of autoregressive (AR)-model interpolation as a solution to the problem. Unlike others, the proposed technique is based on a single SEM image and offers the required accuracy and robustness in estimating SNR values.
  17. Brain early infarct detection using gamma correction extreme-level eliminating with weighting distribution
    Teh V, Sim KS, Wong EK
    Scanning, 2016 Nov;38(6):842-856.
    PMID: 27302216 DOI: 10.1002/sca.21334
    According to the statistic from World Health Organization (WHO), stroke is one of the major causes of death globally. Computed tomography (CT) scan is one of the main medical diagnosis system used for diagnosis of ischemic stroke. CT scan provides brain images in Digital Imaging and Communication in Medicine (DICOM) format. The presentation of CT brain images is mainly relied on the window setting (window center and window width), which converts an image from DICOM format into normal grayscale format. Nevertheless, the ordinary window parameter could not deliver a proper contrast on CT brain images for ischemic stroke detection. In this paper, a new proposed method namely gamma correction extreme-level eliminating with weighting distribution (GCELEWD) is implemented to improve the contrast on CT brain images. GCELEWD is capable of highlighting the hypodense region for diagnosis of ischemic stroke. The performance of this new proposed technique, GCELEWD, is compared with four of the existing contrast enhancement technique such as brightness preserving bi-histogram equalization (BBHE), dualistic sub-image histogram equalization (DSIHE), extreme-level eliminating histogram equalization (ELEHE), and adaptive gamma correction with weighting distribution (AGCWD). GCELEWD shows better visualization for ischemic stroke detection and higher values with image quality assessment (IQA) module. SCANNING 38:842-856, 2016. © 2016 Wiley Periodicals, Inc.
  18. Local dynamic range compensation for scanning electron microscope imaging system by sub-blocking multiple peak HE with convolution
    Sim KS, Teh V, Tey YC, Kho TK
    Scanning, 2016 Nov;38(6):492-501.
    PMID: 26618303 DOI: 10.1002/sca.21285
    This paper introduces new development technique to improve the Scanning Electron Microscope (SEM) image quality and we name it as sub-blocking multiple peak histogram equalization (SUB-B-MPHE) with convolution operator. By using this new proposed technique, it shows that the new modified MPHE performs better than original MPHE. In addition, the sub-blocking method consists of convolution operator which can help to remove the blocking effect for SEM images after applying this new developed technique. Hence, by using the convolution operator, it effectively removes the blocking effect by properly distributing the suitable pixel value for the whole image. Overall, the SUB-B-MPHE with convolution outperforms the rest of methods. SCANNING 38:492-501, 2016. © 2015 Wiley Periodicals, Inc.
  19. Adaptive noise Wiener filter for scanning electron microscope imaging system
    Sim KS, Teh V, Nia ME
    Scanning, 2016 Mar;38(2):148-63.
    PMID: 26235517 DOI: 10.1002/sca.21250
    Noise on scanning electron microscope (SEM) images is studied. Gaussian noise is the most common type of noise in SEM image. We developed a new noise reduction filter based on the Wiener filter. We compared the performance of this new filter namely adaptive noise Wiener (ANW) filter, with four common existing filters as well as average filter, median filter, Gaussian smoothing filter and the Wiener filter. Based on the experiments results the proposed new filter has better performance on different noise variance comparing to the other existing noise removal filters in the experiments. SCANNING 38:148-163, 2016. © 2015 Wiley Periodicals, Inc.
  20. Signal-to-noise ratio estimation using adaptive tuning on the piecewise cubic Hermite interpolation model for images
    Sim KS, Yeap ZX, Tso CP
    Scanning, 2016 Nov;38(6):502-514.
    PMID: 26618491 DOI: 10.1002/sca.21286
    An improvement to the existing technique of quantifying signal-to-noise ratio (SNR) of scanning electron microscope (SEM) images using piecewise cubic Hermite interpolation (PCHIP) technique is proposed. The new technique uses an adaptive tuning onto the PCHIP, and is thus named as ATPCHIP. To test its accuracy, 70 images are corrupted with noise and their autocorrelation functions are then plotted. The ATPCHIP technique is applied to estimate the uncorrupted noise-free zero offset point from a corrupted image. Three existing methods, the nearest neighborhood, first order interpolation and original PCHIP, are used to compare with the performance of the proposed ATPCHIP method, with respect to their calculated SNR values. Results show that ATPCHIP is an accurate and reliable method to estimate SNR values from SEM images. SCANNING 38:502-514, 2016. © 2015 Wiley Periodicals, Inc.
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