Regulatory T cells (Tregs), a subset of CD4+ T cells plays a pivotal role in regulating the immune system. An increase in Treg numbers enables cancer progression by dampening the immune system and allowing tumor cells to evade immune detection and destruction. An increase in Treg numbers and expression of inhibitory cytokines including TGF-β and IL-10 are mechanisms by which Tregs exert their immune suppressive function. However, the presence of Tregs and inhibitory cytokines in oral cancer patients is still unclear. In this study, the presence of circulating Tregs in 39 oral cancer patients and 24 healthy donors was examined by studying the presence of the CD4+CD25hiCD127low cell population in their peripheral blood mononuclear cells using flow cytometry. Serum levels of TGF-β and IL-10 were measured by ELISA. T cell subsets of OSCC patients were found to differ significantly from healthy donors where a decrease in CD8+ cytotoxic T cells and an increase in Tregs (CD4+CD25hiCD127low) were observed. Further, the ratio of CD8+ T cells/Tregs was also decreased in patients compared to healthy donors. The presence of Tregs was accompanied by a decrease in IL-10 but not TGF-β secretion in OSCC patients when compared to donors; in addition, the analysis also revealed that an increased presence of Tregs was accompanied by better patient survival. Amongst OSCC patients, smokers had significantly higher levels of TGF-β. It is apparent that the immune system is compromised in OSCC patients and the characterization of the Treg subpopulation could form a basis for improving our understanding of the perturbations in the immune system that occur during OSCC tumorigenesis.
Biomolecules have been widely investigated as potential therapeutics for various diseases. However their use is limited due to rapid degradation and poor cellular uptake in vitro and in vivo. To address this issue, we synthesized a new nano-carrier system comprising of cholic acid-polyethylenimine (CA-PEI) copolymer micelles, via carbodiimide-mediated coupling for the efficient delivery of small interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA) as model protein. The mean particle size of siRNA- or BSA-loaded CA-PEI micelles ranged from 100-150 nm, with zeta potentials of +3-+11 mV, respectively. Atomic force, transmission electron and field emission scanning electron microscopy demonstrated that the micelles exhibited excellent spherical morphology. No significant morphology or size changes were observed in the CA-PEI micelles after siRNA and BSA loading. CA-PEI micelles exhibited sustained release profile, the effective diffusion coefficients were successfully estimated using a mathematically-derived cylindrical diffusion model and the release data of siRNA and BSA closely fitted into this model. High siRNA and BSA binding and loading efficiencies (95% and 70%, respectively) were observed for CA-PEI micelles. Stability studies demonstrated that siRNA and BSA integrity was maintained after loading and release. The CA-PEI micelles were non cytotoxic to V79 and DLD-1 cells, as shown by alamarBlue and LIVE/DEAD cell viability assays. RT-PCR study revealed that siRNA-loaded CA-PEI micelles suppressed the mRNA for ABCB1 gene. These results revealed the promising potential of CA-PEI micelles as a stable, safe, and versatile nano-carrier for siRNA and the model protein delivery.
OBJECTIVES: To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.
MATERIALS AND METHODS: We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.
RESULTS: There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05).
CONCLUSION: These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.
The native forests of Borneo have been impacted by selective logging, fire, and conversion to plantations at unprecedented scales since industrial-scale extractive industries began in the early 1970s. There is no island-wide documentation of forest clearance or logging since the 1970s. This creates an information gap for conservation planning, especially with regard to selectively logged forests that maintain high conservation potential. Analysing LANDSAT images, we estimate that 75.7% (558,060 km2) of Borneo's area (737,188 km2) was forested around 1973. Based upon a forest cover map for 2010 derived using ALOS-PALSAR and visually reviewing LANDSAT images, we estimate that the 1973 forest area had declined by 168,493 km2 (30.2%) in 2010. The highest losses were recorded in Sabah and Kalimantan with 39.5% and 30.7% of their total forest area in 1973 becoming non-forest in 2010, and the lowest in Brunei and Sarawak (8.4%, and 23.1%). We estimate that the combined area planted in industrial oil palm and timber plantations in 2010 was 75,480 km2, representing 10% of Borneo. We mapped 271,819 km of primary logging roads that were created between 1973 and 2010. The greatest density of logging roads was found in Sarawak, at 0.89 km km-2, and the lowest density in Brunei, at 0.18 km km-2. Analyzing MODIS-based tree cover maps, we estimate that logging operated within 700 m of primary logging roads. Using this distance, we estimate that 266,257 km2 of 1973 forest cover has been logged. With 389,566 km2 (52.8%) of the island remaining forested, of which 209,649 km2 remains intact. There is still hope for biodiversity conservation in Borneo. Protecting logged forests from fire and conversion to plantations is an urgent priority for reducing rates of deforestation in Borneo.
For the first time, a new circuit to extend the linear operation bandwidth of a LTE (Long Term Evolution) power amplifier, while delivering a high efficiency is implemented in less than 1 mm2 chip area. The 950 µm × 900 µm monolithic microwave integrated circuit (MMIC) power amplifier (PA) is fabricated in a 2 µm InGaP/GaAs process. An on-chip analog pre-distorter (APD) is designed to improve the linearity of the PA, up to 20 MHz channel bandwidth. Intended for 1.95 GHz Band 1 LTE application, the PA satisfies adjacent channel leakage ratio (ACLR) and error vector magnitude (EVM) specifications for a wide LTE channel bandwidth of 20 MHz at a linear output power of 28 dBm with corresponding power added efficiency (PAE) of 52.3%. With a respective input and output return loss of 30 dB and 14 dB, the PA's power gain is measured to be 32.5 dB while exhibiting an unconditional stability characteristic from DC up to 5 GHz. The proposed APD technique serves to be a good solution to improve linearity of a PA without sacrificing other critical performance metrics.
Currently, it is well established that cancer arises in chronically inflamed tissue. A number of NOD-like receptors (NLRs) form inflammasomes, intracellular multiprotein complexes critical for generating mature pro-inflammatory cytokines (IL-1β and IL-18). As chronic inflammation of the gastric mucosa is a consequence of Helicobacter pylori infection, we investigated the role of genetic polymorphisms and expression of genes involved in the NLR signalling pathway in H. pylori infection and related gastric cancer (GC).
High prevalence of infection with high-risk human papilloma virus (HPV) ranging from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER) showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.
Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain-Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain-Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.
Cognitive impairment, colloquially termed "chemobrain", occurs in 10-40% of all cancer patients, and is an emerging target of cancer survivorship research.
This study reviews published qualitative studies to explore cognitive impairments or chemobrain among breast cancer survivors, with particular attention given to the impact on quality of life.
Using keywords, we searched ten electronic databases (CINAHL, EMBASE, Proquest, OVID SP, MEDLINE, Oxford Journal, Science Direct, PubMED).
Of 457 papers, seven relevant papers were included. Data was extracted and concepts were analysed using a meta ethnography approach. Four second order intepretations were identified, on the basis of which, four third order intrepretations were constructed. Linked together in a line of argument, was a consistent account on their struggles to self-manage the chemobrain impairments that impact their daily lives. Five concepts emerged from the analysis of the primary findings: i) real experiences of cognitive changes, ii) calls for help, iii) impact of cognitive impairments, iv) coping and v) survivorship and meaning. Further synthesis resulted in four new order intepretations: i) The chemobrain struggle, ii) The substantial impact of chemobrain on life domains, iii) The struggle to readjust and to self manage, and iv) 'thankful yet fearful' representation.
Awareness of cognitive changes were context-dependent on healthcare settings and cultural contexts as strong determinants. Subjects verified the existence of chemobrain but healthcare providers mis-recognised, under-recognised, and sometimes negated it perhaps due to its unknown aetiology. Asian breast cancer survivors appear less vocal than their western counterparts.
The current literature on the lived experiences of how women experienced chemobrain provides a consistent report that chemobrain is real, persistent and with detrimental impacts on quality of life - manifested as a constant struggles. A greater awareness of the effects of chemobrain with improved functional assessment and interventions is warranted.
A maltogenic amylase (MAG1) from alkaliphilic Bacillus lehensis G1 was cloned, expressed in Escherichia coli, purified and characterised for its hydrolysis and transglycosylation properties. The enzyme exhibited high stability at pH values from 7.0 to 10.0. The hydrolysis of β-cyclodextrin (β-CD) produced malto-oligosaccharides of various lengths. In addition to hydrolysis, MAG1 also demonstrated transglycosylation activity for the synthesis of longer malto-oligosaccharides. The thermodynamic equilibrium of the multiple reactions was shifted towards synthesis when the reaction conditions were optimised and the water activity was suppressed, which resulted in a yield of 38% transglycosylation products consisting of malto-oligosaccharides of various lengths. Thin layer chromatography and high-performance liquid chromatography analyses revealed the presence of malto-oligosaccharides with a higher degree of polymerisation than maltoheptaose, which has never been reported for other maltogenic amylases. The addition of organic solvents into the reaction further suppressed the water activity. The increase in the transglycosylation-to-hydrolysis ratio from 1.29 to 2.15 and the increased specificity toward maltopentaose production demonstrated the enhanced synthetic property of the enzyme. The high transglycosylation activity of maltogenic amylase offers a great advantage for synthesising malto-oligosaccharides and rare carbohydrates.
Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8 ± 2.3 versus 11.6 ± 3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3 ± 1.9 versus 12.8 ± 2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.
Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.
Protistan parasites in order to ensure their viability and demonstrate successful progression in their life cycle need to respond towards various environmental stressors. Blastocystis sp. is known to be the most commonly found intestinal protistan parasite in any human stool surveys and has been incriminated to be responsible for diarrhea and bloating stomach. The present study demonstrates for the first time the presence of HSP70 in subtypes of Blastocystis sp. when the cultures were subjected to temperature of 39 and 41 °C where the growth of parasites was reduced to a minimum to majority being granular forms. The growth of parasites exposed to higher temperatures however doubled compared to the controls when the parasites were re-cultured back at 37 °C. Upon thermal stress at 41 °C, subtype 3 and subtype 5 isolates' growth reached up to 2.97 × 10(6) and 3.05 × 10(6) cells/ml compared to their respective controlled culture tubes at 37 °C which peaked only at 1.34 × 10(6) and 1.70 × 10(6) cells/ml respectively. The designed primer set that amplified Blastocystis sp. subtype 7 HSP70 gene in subtypes 1, 3 and 5 was against a conserved region. The gene was amplified at 318 bp. The multiple sequence alignment showed that the targeted sequence length ranges from 291-295 bp. The pair wise alignment result showed that the sequence identity among the four sequence ranges from 88% to 96%. These findings were further evidenced by the up regulation of HSP70 gene in thermal stressed isolates of subtype 3 and 5 at 41 °C. Higher number of granular forms was significantly found in thermal stressed isolates of subtype 3 and 5 which implicates that this life cycle stage has a role in responding to thermal stress.
Forecasting naturally occurring phenomena is a common problem in many domains of science, and this has been addressed and investigated by many scientists. The importance of time series prediction stems from the fact that it has wide range of applications, including control systems, engineering processes, environmental systems and economics. From the knowledge of some aspects of the previous behaviour of the system, the aim of the prediction process is to determine or predict its future behaviour. In this paper, we consider a novel application of a higher order polynomial neural network architecture called Dynamic Ridge Polynomial Neural Network that combines the properties of higher order and recurrent neural networks for the prediction of physical time series. In this study, four types of signals have been used, which are; The Lorenz attractor, mean value of the AE index, sunspot number, and heat wave temperature. The simulation results showed good improvements in terms of the signal to noise ratio in comparison to a number of higher order and feedforward neural networks in comparison to the benchmarked techniques.
In this paper, a Semantic Web service matchmaker called UltiMatch-NL is presented. UltiMatch-NL applies two filters namely Signature-based and Description-based on different abstraction levels of a service profile to achieve more accurate results. More specifically, the proposed filters rely on semantic knowledge to extract the similarity between a given pair of service descriptions. Thus it is a further step towards fully automated Web service discovery via making this process more semantic-aware. In addition, a new technique is proposed to weight and combine the results of different filters of UltiMatch-NL, automatically. Moreover, an innovative approach is introduced to predict the relevance of requests and Web services and eliminate the need for setting a threshold value of similarity. In order to evaluate UltiMatch-NL, the repository of OWLS-TC is used. The performance evaluation based on standard measures from the information retrieval field shows that semantic matching of OWL-S services can be significantly improved by incorporating designed matching filters.
Signal transducers and activators of transcription (STAT) proteins are key signalling molecules in metazoans, implicated in various cellular processes. Increased research in the field has resulted in the accumulation of STAT sequence and structure data, which are scattered across various public databases, missing extensive functional annotations, and prone to effort redundancy because of the dearth of community sharing. Therefore, there is a need to integrate the existing sequence, structure and functional data into a central repository, one that is enriched with annotations and provides a platform for community contributions. Herein, we present STATdb (publicly available at http://statdb.bic.nus.edu.sg/), the first integrated resource for STAT sequences comprising 1540 records representing the known STATome, enriched with existing structural and functional information from various databases and literature and including manual annotations. STATdb provides advanced features for data visualization, analysis and prediction, and community contributions. A key feature is a meta-predictor to characterise STAT sequences based on a novel classification that integrates STAT domain architecture, lineage and function. A curation policy workflow has been devised for regulated and structured community contributions, with an update policy for the seamless integration of new data and annotations.
Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤ 1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance.
Wind turbine noise is one of the major obstacles for the widespread use of wind energy. Noise tone can greatly increase the annoyance factor and the negative impact on human health. Noise annoyance caused by wind turbines has become an emerging problem in recent years, due to the rapid increase in number of wind turbines, triggered by sustainable energy goals set forward at the national and international level. Up to now, not all aspects of the generation, propagation and perception of wind turbine noise are well understood. For a modern large wind turbine, aerodynamic noise from the blades is generally considered to be the dominant noise source, provided that mechanical noise is adequately eliminated. The sources of aerodynamic noise can be divided into tonal noise, inflow turbulence noise, and airfoil self-noise. Many analytical and experimental acoustical studies performed the wind turbines. Since the wind turbine noise level analyzing by numerical methods or computational fluid dynamics (CFD) could be very challenging and time consuming, soft computing techniques are preferred. To estimate noise level of wind turbine, this paper constructed a process which simulates the wind turbine noise levels in regard to wind speed and sound frequency with adaptive neuro-fuzzy inference system (ANFIS). This intelligent estimator is implemented using Matlab/Simulink and the performances are investigated. The simulation results presented in this paper show the effectiveness of the developed method.
The worldwide depletion of major fish stocks through intensive industrial fishing is thought to have profoundly altered the trophic structure of marine ecosystems. Here we assess changes in the trophic structure of the English Channel marine ecosystem using a 90-year time-series (1920-2010) of commercial fishery landings. Our analysis was based on estimates of the mean trophic level (mTL) of annual landings and the Fishing-in-Balance index (FiB). Food webs of the Channel ecosystem have been altered, as shown by a significant decline in the mTL of fishery landings whilst increases in the FiB index suggest increased fishing effort and fishery expansion. Large, high trophic level species (e.g. spurdog, cod, ling) have been increasingly replaced by smaller, low trophic level fish (e.g. small spotted catsharks) and invertebrates (e.g. scallops, crabs and lobster). Declining trophic levels in fisheries catches have occurred worldwide, with fish catches progressively being replaced by invertebrates. We argue that a network of fisheries closures would help rebalance the trophic status of the Channel and allow regeneration of marine ecosystems.
In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model.