Host Immune Responses to Arthritogenic Alphavirus Infection, with Emphasis on Type I IFN Responses

Arthritogenic alphaviruses, such as Ross River virus, chikungunya virus and O’nyong-nyong virus, cause endemic disease globally and are a major public health concern. The hallmarks of arthritogenic alphavirus disease are debilitating pain, and potentially chronic inflammation of the muscles, thus influencing quality of life. The type I IFN response is a major component of the innate immune response against arthritogenic alphaviruses, and is essential in inhibiting viral replication and dissemination. Type I IFNs are induced during early stages of infection and are essential for the activation of the antiviral innate immune response. They also link the innate immune response and the activation of adaptive immunity. This review focuses on the host immune response, particularly that involving type I IFN, in arthritogenic alphavirus disease

`Maser-in-a-Shoebox': a portable plug-and-play maser device at room-temperature and zero magnetic-field

Masers, the microwave analogues of lasers, have seen a renaissance owing to the discovery of gain media that mase at room-temperature and zero-applied magnetic field. However, despite the ease with which the devices can be demonstrated under ambient conditions, achieving the ubiquity and portability which lasers enjoy has to date remained challenging. We present a maser device with a miniaturized maser cavity, gain material and laser pump source that fits within the size of a shoebox. The gain medium used is pentacene-doped in para-terphenyl and it is shown to give a strong masing signal with a peak power of -5 dBm even within a smaller form factor. The device is also shown to mase at different frequencies within a small range of 1.5 MHz away from the resonant frequency. The portability and simplicity of the device, which weighs under 5 kg, paves the way for demonstrators particularly in the areas of low-noise amplifiers, quantum sensors, cavity quantum electrodynamics and long-range communications

N-Heteroacenes as an Organic Gain Medium for Room-Temperature Masers

The development of future quantum devices such as the maser, i.e., the microwave analog of the laser, could be well-served by the exploration of chemically tunable organic materials. Current iterations of room-temperature organic solid-state masers are composed of an inert host material that is doped with a spin-active molecule. In this work, we systematically modulated the structure of three nitrogen-substituted tetracene derivatives to augment their photoexcited spin dynamics and then evaluated their potential as novel maser gain media by optical, computational, and electronic paramagnetic resonance (EPR) spectroscopy. To facilitate these investigations, we adopted an organic glass former, 1,3,5-tri(1-naphthyl)benzene to act as a universal host. These chemical modifications impacted the rates of intersystem crossing, triplet spin polarization, triplet decay, and spin–lattice relaxation, leading to significant consequences on the conditions required to surpass the maser threshold

In silico-guided sequence modifications of K-ras epitopes improve immunological outcome against G12V and G13D mutant KRAS antigens

Background: Somatic point substitution mutations in the KRAS proto-oncogene primarily affect codons 12/13 where glycine is converted into other amino acids, and are highly prevalent in pancreatic, colorectal, and non-small cell lung cancers. These cohorts are non-responsive to anti-EGFR treatments, and are left with non-specific chemotherapy regimens as their sole treatment options. In the past, the development of peptide vaccines for cancer treatment was reported to have poor AT properties when inducing immune responses. Utilization of bioinformatics tools have since become an interesting approach in improving the design of peptide vaccines based on T- and B-cell epitope predictions. Methods: In this study, the region spanning exon 2 from the 4th to 18th codon within the peptide sequence of wtKRAS was chosen for sequence manipulation. Mutated G12V and G13D K-ras controls were generated in silico, along with additional single amino acid substitutions flanking the original codon 12/13 mutations. IEDB was used for assessing human and mouse MHC class I/II epitope predictions, as well as linear B-cell epitopes predictions, while RNA secondary structure prediction was performed via CENTROIDFOLD. A scoring and ranking system was established in order to shortlist top mimotopes whereby normalized and reducing weighted scores were assigned to peptide sequences based on seven immunological parameters. Among the top 20 ranked peptide sequences, peptides of three mimotopes were synthesized and subjected to in vitro and in vivo immunoassays. Mice PBMCs were treated in vitro and subjected to cytokine assessment using CBA assay. Thereafter, mice were immunized and sera were subjected to IgG-based ELISA. Results: In silico immunogenicity prediction using IEDB tools shortlisted one G12V mimotope (68-V) and two G13D mimotopes (164-D, 224-D) from a total of 1,680 candidates. Shortlisted mimotopes were predicted to promote high MHC-II and -I affinities with optimized B-cell epitopes. CBA assay indicated that: 224-D induced secretions of IL-4, IL-5, IL-10, IL-12p70, and IL-21; 164-D triggered IL-10 and TNF-α; while 68-V showed no immunological responses. Specific-IgG sera titers against mutated K-ras antigens from 164-D immunized Balb/c mice were also elevated post first and second boosters compared to wild-type and G12/G13 controls. Discussion: In silico-guided predictions of mutated K-ras T- and B-cell epitopes were successful in identifying two immunogens with high predictive scores, Th-bias cytokine induction and IgG-specific stimulation. Developments of such immunogens are potentially useful for future immunotherapeutic and diagnostic applications against KRAS(+) malignancies, monoclonal antibody production, and various other research and development initiatives

Antioxidative properties of selected microencapsulated plants powder prepared using ultrasonic spray-drying technique

Ultrasonic spray drier technology has been practice because of its numerous advantages, including providing more uniform droplets and reducing bioactive compounds damages. This study was aimed to measure the antioxidant properties of several microencapsulated plants powder (MPP) prepared using ultrasonic spray dying technique. The plant samples were treated using ultrasonic spray drier at 80°C inlet temperatures and 10% of gum Arabic relative to solid content. The collected MPP were analysed for their antioxidant activities. The plants use in this study were C. ternatea, M. indica, S. rebaudiana, P. macrocarpa, K. salvarezii and R. apiculata, All MPP showed somewhat very promising high antioxidative activities with C. ternatea significantly exhibited the highest (P<0.05) antioxidant power in nearly all antioxidative test analysis performed. On the other hand, M. indica showed the least ability in antioxidant power and the content of bioactive compounds. Results of the study point that the production of MPP and microcapsules is feasible as a functional ingredient in food industry as it can retain the antioxidative properties, which could lead to a more sustainable usage of natural resources

The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

Abstract: Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations

The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

Abstract: Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations

The importance of Au⋯π(aryl) interactions in the formation of spherical aggregates in binuclear phosphane gold(I) complexes of a bipodal thiocarbamate dianion: a combined crystallographic and computational study, and anti-microbial activity

Binuclear phosphane gold(I) complexes of a bipodal thiocarbamate dianion, (R3PAu)2L, R = Et (1), Ph (2) and Cy (3), where LH2 is {1,4-[MeOC([double bond, length as m-dash]S)N(H)]2C6H4}, have been synthesised, and characterised spectroscopically (NMR and IR) and by X-ray crystallography. The gold atoms are linearly coordinated within a P-,S-donor set, and are oriented toward the central ring to form intramolecular Au⋯π(aryl) interactions, rather than the intramolecular Au⋯O interactions normally observed in mononuclear analogues. This phenomenon has been investigated by theory (LC-ωPBE-XDM) for 1 which revealed that the geometry optimised species with two Au⋯π(aryl) interactions is more stable by at least 12 kcal mol−1 compared to conformations having one or more Au⋯O interactions instead. The disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods were used to observe the inhibitory effect of complexes 1–3. The disk diffusion results demonstrated that 1 exhibited a broad spectrum of anti-bacterial activity toward 24 strains of Gram-positive and Gram-negative bacteria. By contrast, the anti-bacterial activity of 2 and 3 was limited to Gram-positive bacteria. Further evaluation showed that 1 exhibited marked bactericidal activity against B. cereus, B. subtilis, E. faecalis, L. monocytogenes, S. aureus, S. saprophyticus and methicillin resistant S. aureus cf. standard antibiotics tetracycline and chloramphenicol

Fabrication, testing and performance enhancement of a small scale tidal current turbine / Ng Kai Wern

The working concept of a horizontal-axis tidal current turbine (HATCT) is similar to that of wind turbines. The technology used in wind turbine can be readily transferred to tidal current turbines. This is exactly what is going on at the moment in HATCTs industry. Malaysia is a country that can benefit from tidal current turbine, especially in the Straits of Malacca. The current flow in the Straits of Malacca varies from 0.5m/s to 1.5m/s, and reaches 2.0m/s or above at some localities. Considering the benchmark of economic power generation for tidal current turbines to be around 1.5m/s, harnessing tidal current energy looks promising for Malaysia. However, to-date, no study on creating a workable turbine has been reported for Malaysia. Therefore, it is the aim of the current research to study workability and performance of an operational tidal current turbine for Malaysia. The testing and modification of turbine were done with the sponsor and help of Laison Engineering Sdn. Bhd. A 800mm five-bladed turbine was tested at Pangkor Island. The original setting of the prototype turbine was not able to produce steady power output. But after a few modifications on the generator and shaft, a power coefficient of approximately 0.32 was achieved with current velocity of 0.25m/s. Besides the fabrication and testing of the turbine, an innovative method to improve the efficiency of tidal current turbine has also been studied. The innovative method was the use of hydrophobic antifouling paint. Antifouling paint is an important protection measure for tidal current turbine to against marine bio-fouling. Marine bio-fouling has deteriorating effects on the performance of tidal current turbine once they are attached on the turbine blades. Hydrophobic anti-fouling paint is one of the common types of anti-fouling paint that is used. Interestingly, its hydrophobicity has the ability to reduce friction drag over a surface. As such, hydrophobic anti-fouling can potentially provide performance enhancement for a tidal current turbine, meanwhile protects turbine blades from marine bio-fouling. Two commercial hydrophobic antifouling coatings, Biocyl and a normal hydrophobic coating, Always Dry were used. Experiment has been conducted to understand the effects of hydrophobic coating on hydrofoils and a 350mm diameter three-bladed turbine. It was found that both Biocyl and Always Dry lower the drag coefficient of NACA 63418 by an average of 3% and 3.5%. Biocyl has improved the revolution per minute of the turbine by an average of 1.3%, whereas Always Dry has improved the revolution per minute of the turbine by an average of 2.5%. Last but not least, two commercial antifouling paints, namely Bioycl and Palccoat, have been tested to understand their ability to protect tidal current turbine from marine bio-fouling activities in Pangkor Island. The field test results show that with these anti-fouling paints, the development of thin film on turbine blade can be postponed to 3~4weeks. Up to this stage, the thin film can still be cleaned. However, when barnacles started to grow on the blade, it is difficult to remove the barnacle by simple cleaning

Study of the application of smart materials on flexible wing UAV

In recent years, UAV has been popular in the military and homeland security field for recon and surveillance purposes, with occasional search and rescue mission. However, conventional UAVs are expensive, heavy and bulky. Nonetheless, it requires more than one crew to operate it. With the demand of smaller, lighter, cheaper as well as instant launching single man operation UAV getting more, mini‐UAV was developed. However, the issues with mini‐UAVs is that their flight altitude is lower than those conventional UAVs. This causes the mini‐UAVs more vulnerable to severe weather condition. In order to overcome this, flexible wings made from layers of carbon fibers were invented. It is proved that flexible wing membrane is easier to maneuver in the windy weather thanks to the adaptive washout mechanism that came along with it. Furthermore, flexible wings can be wrapped around the mini‐UAV fuselage for storage and can be easily deployed. The purpose of this project is to improve the controllability of this flexible wing UAV due to the drawback on lack of aileron on the wings as it is not practical to have one. Flexible wing UAV depends solely on the control surfaces that is available at the empennage, be it a pair of ruddervators or elevons. Limited choices were given due to the constraints of the flexible wings. Torque rods are first to be eliminate as it will prevent the wings from folding during storage. Hence, smart materials became the first choice. With new actuation methods, new controls are needed.Bachelor of Engineering (Mechanical Engineering