Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog

Natural killer (NK) cells have been implicated in early immune responses against certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of class I major histocompatibility complex (MHC) expression in infected cells; however, it has been proposed that a class I MHC homolog encoded by CMV, UL18, may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In this study, we examined the role of UL18 in NK cell recognition and lysis using fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by using cell lines transfected with the UL18 gene. In both systems, the expression of UL18 resulted in the enhanced killing of target cells. We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell–mediated cytotoxicity

Utilizing open source software running in inexpensive high performance computing system for cfd applications

The high cost of conducting research is a significant issue for the successfulness of any research project. For research activities involving flow simulation, the licensing fee for the numerical software and the cost to acquire powerful machine are the main factors contributing to the high cost. This paper reports our experiences in setting up a cost effective way of doing computational fluid dynamics (CFD). The actions involve two areas, i.e., software and hardware. For the software, open source softwares are utilized, particularly the OpenFOAM(r) as the CFD package. For the hardware, a parallel computer made from a cluster of inexpensive desktop computer is constructed. This architecture is found able to meet our requirement in investigating various flow problems that include aeroacoustics, vibration and wind engineering for ventilation

Sub-Nyquist Field Trial Using Time Frequency Packed DP-QPSK Super-Channel Within Fixed ITU-T Grid

Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR=15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE*d product of 9254 bit/s/Hz*km was achieved

Extending Feynman's Formalisms for Modelling Human Joint Action Coordination

The recently developed Life-Space-Foam approach to goal-directed human action deals with individual actor dynamics. This paper applies the model to characterize the dynamics of co-action by two or more actors. This dynamics is modelled by: (i) a two-term joint action (including cognitive/motivatonal potential and kinetic energy), and (ii) its associated adaptive path integral, representing an infinite--dimensional neural network. Its feedback adaptation loop has been derived from Bernstein's concepts of sensory corrections loop in human motor control and Brooks' subsumption architectures in robotics. Potential applications of the proposed model in human--robot interaction research are discussed. Keywords: Psycho--physics, human joint action, path integralsComment: 6 pages, Late

Seasonal and spatial dynamics of the primary vector of plasmodium knowlesi within a major transmission focus in Sabah, Malaysia

Background The simian malaria parasite Plasmodium knowlesi is emerging as a public health problem in Southeast Asia, particularly in Malaysian Borneo where it now accounts for the greatest burden of malaria cases and deaths. Control is hindered by limited understanding of the ecology of potential vector species. Methodology/Principal Findings We conducted a one year longitudinal study of P. knowlesi vectors in three sites within an endemic area of Sabah, Malaysia. All mosquitoes were captured using human landing catch. Anopheles mosquitoes were dissected to determine, oocyst, sporozoites and parous rate. Anopheles balabacensis is confirmed as the primary vector of. P. knowlesi (using nested PCR) in Sabah for the first time. Vector densities were significantly higher and more seasonally variable in the village than forest or small scale farming site. However An. balabacensis survival and P. knowlesi infection rates were highest in forest and small scale farm sites. Anopheles balabacensis mostly bites humans outdoors in the early evening between 1800 to 2000hrs. Conclusions/Significance This study indicates transmission is unlikely to be prevented by bednets. This combined with its high vectorial capacity poses a threat to malaria elimination programmes within the region. Author Summary The first natural infection of Plasmodium knowlesi was reported 40 years ago. At that time it was perceived that the infection would not affect humans. However, now P. knowlesi is the predominant malaria species (38% of the cases) infecting people in Malaysia and is a notable obstacle to malaria elimination in the country. Plasmodium knowlesi has also been reported from all countries in Southeast Asia with the exception of Lao PDR and Timor Leste. In Sabah, Malaysian Borneo cases of human P. knowlesi are increasing. Thus, a comprehensive understanding of the bionomics of the vectors is required so as to enable proper control strategies. Here, we conducted a longitudinal study in Kudat district, Sabah, to determine and characterize the vectors of P. knowlesi within this transmission foci. Anopheles balabacensis was the predominant mosquito in all study sites and is confirmed as vector for P. knowlesi and other simian malaria parasites. The peak biting time was in the early part of the evening between1800 to 2000. Thus, breaking the chain of transmission is an extremely challenging task for the malaria elimination programme

A Potent and Effective Suicidal Listeria Vaccine Platform.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection

Effect of different drying methods and solvent ratios on biological activities of Phyllanthus acidus extracts

The main purpose of this study was to evaluate the antioxidant and α-glucosidase inhibitory activities of Phyllanthus acidus. The P. acidus fruits were dried using three different methods, namely oven (OD), air (AD) and freeze (FD) dryings and extracted with ethanol at different ratios (50 and 100%). The proximate analysis and total phenolic content (TPC) as well as free radical scavenging and α-glucosidase inhibitory activities were determined. The proximate analysis of P. acidus fruit indicated that all the dried samples contained potential nutrient contents. The highest TPC value, α-glucosidase inhibitory and antioxidant activities were observed for 50% ethanolic extract from OD method with TPC value of 28.39 mg GAE/g dried extract, IC50 value of 12.394 μg/mL and 64.17% inhibition, respectively. The study revealed that phenolic compounds could be the main contributors to the antioxidant and α-glucosidase inhibitory activities based on the Pearson correlation coefficients with R values of 95.0 and 73.8%, respectively. The study could provide scientific evidence for some folk uses in the treatment of diseases related to the production of reactive oxygen species and oxidative stress

Exterior noise due to interaction of tyre-thermoplastic transverse rumble strips

Transverse rumble strips (TRS) are a common choice to reduce vehicle speed and increase driver alertness on roadways. However, there is a potential trade-off using them on rural roadway due to the noise problem created when vehicles go over the strips. The present study investigated the noise level, spectral analysis, and the possible noise generation mechanism when the TRS is hit by a vehicle. Tenraised- rumbler (RR) and three-layer-overlapped (TLO) TRS were selected in this study as they have received complaints from the public. Results showed that RR generated a relatively higher noise and impulse at a low speed, and increased sound level in each octave band. Based on these results, RR may irritate human ears even when the vehicle travels at a low speed. It was found that RR increased all noise generation mechanisms of tyre-pavement interaction whilst TLO increased structural resonance, sidewall and surface texture vibration

Cost-benefit analysis for commissioning decisions in GEO600

Gravitational wave interferometers are complex instruments, requiring years of commissioning to achieve the required sensitivities for the detection of gravitational waves, of order 10^-21 in dimensionless detector strain, in the tens of Hz to several kHz frequency band. Investigations carried out by the GEO600 detector characterisation group have shown that detector characterisation techniques are useful when planning for commissioning work. At the time of writing, GEO600 is the only large scale laser interferometer currently in operation running with a high duty factor, 70%, limited chiefly by the time spent commissioning the detector. The number of observable gravitational wave sources scales as the product of the volume of space to which the detector is sensitive and the observation time, so the goal of commissioning is to improve the detector sensitivity with the least possible detector down time. We demonstrate a method for increasing the number of sources observable by such a detector, by assessing the severity of non-astrophysical noise contaminations to efficiently guide commissioning. This method will be particularly useful in the early stages and during the initial science runs of the aLIGO and adVirgo detectors, as they are brought up to design performance.Comment: 17 pages, 17 figures, 2 table

Brane World Effective Action at Low Energies and AdS/CFT Correspondence

A low energy iteration scheme to study nonlinear gravity in the brane world is developed. As a result, we obtain the brane world effective action at low energies. The relation between the geometrical approach and the approach using the AdS/CFT correspondence is also clarified. In particular, we find generalized dark radiation as homogeneous solutions in our iteration scheme. Moreover, the precise correspondence between the bulk geometry and the brane effective action is established, which gives a holographic view of the brane world.Comment: Revtex4, 12 pages, references added. Version accepted for publicaton in Phys. Rev.