In silico structural modeling and quality assessment of Plasmodium knowlesi apical membrane antigen 1 using comparative protein models.

Plasmodium knowlesi is the most common zoonotic parasite associated with human malaria infection in Malaysia. Apical membrane antigen 1 (AMA1) protein in the parasite plays a critical role in parasite invasion into host cells. To date, there is no complete three-dimensional ectodomain structure of P. knowlesi AMA1 (PkAMA1) protein. The knowledge of a protein structure is important to understand the protein molecular functions. Three in silico servers with respective structure prediction methods were used in this study, i.e., SWISS-MODEL for homology modeling and Phyre2 for protein threading, which are template-based modeling, while I-TASSER for template-free ab initio modeling. Two query sequences were used in the study, i.e., native ectodomain of PkAMA1 strain H protein designated as PkAMA1-H and a modified PkAMA1 (mPkAMA1) protein sequence in adaptation for Pichia pastoris expression. The quality of each model was assessed by ProSA-web, QMEAN and SAVES v6.0 (ERRAT, Verify3D and Ramachandran plot) servers. Generated models were then superimposed with two models of Plasmodium AMA1 deposited in Protein Data Bank (PDB), i.e., PkAMA1 (4UV6.B) and Plasmodium vivax AMA1 (PvAMA1, 1W81) protein structures for similarity assessment, quantified by root-meansquare deviation (RMSD) value. SWISS-MODEL, Phyre2 and I-TASSER server generated two, one and five models, respectively. All models are of good quality according to ProSA-web assessment. Based on the average values of model quality assessment and superimposition, the models that recorded highest values for most parameters were selected as best predicted models, i.e., model 2 for both PkAMA1-H and mPkAMA1 from SWISS-MODEL as well as model 1 of PkAMA1-H and model 3 of mPkAMA1 from I-TASSER. Template-based method is useful if known template is available, but template-free method is more suitable if there is no known available template. Generated models can be used as guidance in further protein study that requires protein structural data, i.e., protein-protein interaction study.

Bioinformatics characterization of Plasmodium knowlesi apical membrane antigen 1 (PkAMA1) for multi-epitope vaccine design.

Malaria caused by Plasmodium knowlesi species has become a public health concern, especially in Malaysia. Plasmodium knowlesi parasite which originates from the macaque species, infects human through the bite of the Anopheles mosquitoes. Research on malaria vaccine has been a continuous effort to eradicate the malaria infection, yet there is no vaccine against P. knowlesi malaria to date. Apical membrane antigen 1 (AMA1) is a unique surface protein of all apicomplexan parasites that plays a crucial role in parasite-host cell invasion and thus has been a long-standing malaria vaccine candidate. The selection of protective epitopes in silico has led to significant advances in the design of the vaccine. The present study aimed to employ bioinformatics tools to predict the potential immunogenic B- and T-cell epitopes in designing malaria vaccine targeting P. knowlesi AMA1 (PkAMA1). B-cell epitopes were predicted using four bioinformatics tools, i.e., BepiPred, ABCpred, BcePred, and IEDB servers whereas T-cell epitopes were predicted using two bioinformatics servers, i.e., NetMHCpan4.1 and NetMHCIIpan-4.0 targeting human major histocompatibility complex (MHC) class I and class II molecules, respectively. The antigenicity of the selected epitopes computed by both B- and T-cell predictors were further analyzed using the VaxiJen server. The results demonstrated that PkAMA1 protein encompasses multi antigenic regions that have the potential for the development of multi-epitope vaccine. Two B- and T-cell epitopes consensus regions, i.e., NSGIRIDLGEDAEVGNSKYRIPAGKCP (codons 28-54) and KTHAASFVIAEDQNTSY RHPAVYDEKNKT (codons 122-150) at domain I (DI) of PkAMA1 were reported. Advancement of bioinformatics in characterization of the target protein may facilitate vaccine development especially in vaccine design which is costly and cumbersome process. Thus, comprehensive B-cell and T-cell epitope prediction of PkAMA1 offers a promising pipeline for the development and design of multi-epitope vaccine against P. knowlesi.

Unexplained ascites, a sign for neuroendocrine carcinoma.

Neuroendocrine neoplasm is an epithelial neoplasm with predominant neuroendocrine differentiation that can arise from many organs in the body. We reported a rare case of gastric neuroendocrine carcinoma which accounts for less than 1% of all gastric tumours that is associated with poor prognosis. The recognition of this rare tumour in early stage is challenging and high suspicious into it might bring to early detection and so forth might improve the prognostication.

A quasi two-dimensional model for sound attenuation by the sonic crystals.

Sound propagation in the sonic crystal (SC) along the symmetry direction is modeled by sound propagation through a variable cross-sectional area waveguide. A one-dimensional (1D) model based on the Webster horn equation is used to obtain sound attenuation through the SC. This model is compared with two-dimensional (2D) finite element simulation and experiment. The 1D model prediction of frequency band for sound attenuation is found to be shifted by around 500 Hz with respect to the finite element simulation. The reason for this shift is due to the assumption involved in the 1D model. A quasi 2D model is developed for sound propagation through the waveguide. Sound pressure profiles from the quasi 2D model are compared with the finite element simulation and the 1D model. The result shows significant improvement over the 1D model and is in good agreement with the 2D finite element simulation. Finally, sound attenuation through the SC is computed based on the quasi 2D model and is found to be in good agreement with the finite element simulation. The quasi 2D model provides an improved method to calculate sound attenuation through the SC.

PCR-RFLP genotyping of C1q mutations and single nucleotide polymorphisms in Malaysian patients with systemic lupus erythematosus.

Five types of known mutations within the C1q gene [located at C1qA-Gln186 (C >T), C1qB-Gly15 (G >A), C1qB-Arg150 (C >T), C1qC-Gly6 (G >A), and C1qC-Arg41 (C >T)] and two SNPs located at C1qA-Gly70 (G/A) and C1qC-Pro14 (T/C) were screened in a multiracial Malaysian population. One hundred thirty patients with systemic lupus erythematosus (SLE) and 130 matched healthy control subjects were genotyped using PCR-RFLP methods. We found no occurrence of the five types of mutations in either the homozygous or heterozygous form among the 260 samples studied. Statistical analysis also revealed that there were no significant associations observed in the genotype distributions and allele frequencies among the patients with SLE and healthy control subjects with both C1qA-Gly70 (G/A) and C1qC-Pro14 (T/C) SNPs. Overall, C1q deficiency was not proven as a primary causative genetic predisposition factor for SLE in the Malaysian population.

A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population.

The aim of the present study was to investigate the association of C4 gene mutations with systemic lupus erythematosus, in 130 Malaysian SLE patients and 130 healthy controls. Generally, various PCR approaches were used to screen the mutations of the C4 genes, which included 2 bp (+TC) insertions at codon 1213 in exon 29, 1 bp deletions (-C) at codon 811 in exon 20, 1 bp (-C), 2 bp (-GT) deletions at codons 522 and 497 in exon 13 and null alleles. No mutations located at exons 13, 20 and 29 of the C4 gene, were detected amongst the patient and control samples in this study. C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients. Overall, our results do not demonstrate a significant association to these known C4 mutations identified by previous studies, in the Malaysian scenario.

Postgraduate medical education and specialist training in Singapore.

The Singapore Medical School celebrates its Centenary in 2005. This historical review is presented on Singapore's postgraduate medical education and specialist training programmes. The special informal role of the Alumni Association and its members during the early years and soon after World War II is highlighted. Postgraduate education and specialist training was more formalised only during the challenging years when Singapore became more autonomous and politically independent with the establishment of the Academy of Medicine, the School's postgraduate medical studies, the Singapore Medical Association, specialist societies and, more recently, the College of Family Physicians. Specialist training programmes and the process of specialist accreditation are also outlined. While Singapore has gone far towards developing a comprehensive programme of postgraduate medical education and specialist training, the process is still evolving and can be improved upon. As long as we keep pace with relevant and realistic strategies, the future for postgraduate medical training and specialist training should be assured.

Characterization and third-order optical nonlinearities of uniform surface-modified CdS nanoparticles.

Size-controlled uniform surface-capped CdS nanoparticles were readily prepared by an improved inverse microemulsion technique using hexanethiol as co-surfactant. The third-order optical nonlinearities were studied for the first time by newly-developed Z-scan technique, from which the enhanced nonlinear optical responses were observed after heat-treatment.

AFM imaging and characterization of latex particles formed by copolymerization of styrene and poly(ethylene oxide) macromonomer.

A new type of latex particle was prepared by copolymerization of styrene and poly(ethylene oxide) macromonomer. By controlling the concentration of styrene in reaction mixtures, several latexes with different grain sizes were obtained. The packing patterns of the latex films as well as shapes and sizes of the latex particles were measured with atomic force microscopy (AFM). AFM images revealed that the grain sizes of the latexes increase with increasing concentration of styrene. At a higher styrene concentration (10 wt%), the latex showed a rather homogenous distribution of grain sizes. Lateral force microscopy (LFM) was used to reveal frictional features of latex particles. Contact and non-contact mode AFM were employed to image the same sample of the latex films. The results show that AFM working in non-contact mode can be used to effectively eliminate the horizontal-line-like artifacts, which may obscure AFM images.

Processing of hydroxyapatite via microemulsion and emulsion routes.

Hydroxyapatite powders have been prepared by reacting CaCl2 and (NH4)2HPO4 in bicontinuous microemulsion, inverse microemulsion and emulsion, which have the same components as cyclohexane, non-ionic surfactant (NP5 + NP9) and aqueous solution. The characteristics of the resulting hydroxyapatite powders, such as the particle size, particle size distribution, chemical homogeneity and the degree of particle agglomeration, are strongly affected by the structure of the reaction medium. Both bicontinuous and inverse microemulsions led to the formation of much finer hydroxyapatite powders than that prepared from the emulsion composition. The two fine hydroxyapatite powders are sintered to a relative density of >95% theoretical density at 1000 degrees C, compared with a relative density of <73% theoretical density for the emulsion-derived one. The two microemulsion-derived hydroxyapatites also exhibit a higher sintered density and are more refined in grain size than that of the emulsion-derived one when sintered at 1200 degrees C for 2h.

Poly(sodium acrylamidoalkanoates) in water treatment.

Poly(sodium 6-acrylamidocaproate), poly(sodium 11-acrylamidoundecanoate), poly(sodium 11-N-methylacrylamidoundecanoate) and poly(sodium 11-N-ethylacrylamidoundecanoate) have been synthesized. The performance of these anionic polyelectrolytes as coagulant aids in water treatment was assessed by the jar test. The effects of polymer dosage and pH on their performances were investigated in order to establish the optimum flocculation conditions. The effectiveness of these polyelectrolytes as well as a commercially available cationic polyamine organic coagulant aid was compared in terms of floc size, settling rate and the quality of treated water. Poly(sodium 6-acrylamidocaproate) and poly(sodium 11-acrylamidoundecanoate) were superior to poly(sodium 11-N-methylacrylamidoundecanoate) and poly(sodium 11-N-ethylacrylamidoundecanoate), and they are as effective as the commercial cationic coagulant aid.

Behavioral inhibition and electrodermal activity during deception.

We tested the assumption that the act of inhibiting ongoing behavior requires physiological work. In a guilty knowledge test (GKT) paradigm, subjects were induced to attempt to deceive the experimenter on two separate occasions while electrodermal activity was measured. For 20 of the 30 subjects, overt behaviors (changes in eye movement and facial expression) were recorded during the second GKT. Results indicated that the incidence of behaviors decreased during their deceptive responses. This behavioral inhibition coincided with increases in skin conductance level. In addition to suggesting nonverbal correlates of deception, the results indicate that long-term behavioral inhibition may be a factor in psychosomatic disease.