Signal Peptide-Dependent Inhibition of MHC Class I Heavy Chain Translation by Rhesus Cytomegalovirus

The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC) expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference

Killer immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Aged Subjects: Observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST)

BACKGROUND: Natural Killer Cells (NK) play an important role in detection and elimination of virus-infected, damaged or cancer cells. NK cell function is guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with altered HLA self-antigens, damaged by viruses or tumours. We have previously described increased numbers of NK and NK-related subsets in association with sIL-2R cytokine serum levels in BELFAST octo/nonagenarians. We hypothesised that changes in KIR A and B haplotype gene frequencies could explain the increased cytokine profiles and NK compartments previously described in Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) octo/nonagenarians, who show evidence of ageing well. RESULTS: In the BELFAST study, 24% of octo/nonagenarians carried the KIR A haplotype and 76% KIR B haplotype with no differences for KIR A haplogroup frequency between male or female subjects (23% v 24%; p=0.88) or for KIR B haplogroup (77% v 76%; p=0.99). Octo/nonagenarian KIR A haplotype carriers showed increased NK numbers and percentage compared to Group B KIR subjects (p=0.003; p=0.016 respectively). There were no KIR A/ B haplogroup-associated changes for related CD57+CD8 ((high or low)) subsets. Using logistic regression, KIR B carriers were predicted to have higher IL-12 cytokine levels compared to KIR A carriers by about 3% (OR 1.03, confidence limits CI 0.99–1.09; p=0.027) and 14% higher levels for TGF-β (active), a cytokine with an anti-inflammatory role, (OR 1.14, confidence limits CI 0.99–1.09; p=0.002). CONCLUSION: In this observational study, BELFAST octo/nonagenarians carrying KIR A haplotype showed higher NK cell numbers and percentage compared to KIR B carriers. Conversely, KIR B haplotype carriers, with genes encoding for activating KIRs, showed a tendency for higher serum pro-inflammatory cytokines compared to KIR A carriers. While the findings in this study should be considered exploratory they may serve to stimulate debate about the immune signatures of those who appear to age slowly and who represent a model for good quality survivor-hood

Recommendations for long-term luminance distribution measurements:the spatial resolution

Currently, luminance distribution measurement devices are increasingly used because there is high relevancy in the luminance distribution to the perceived visual comfort, also technology is maturing. It is now feasible to conduct long-term measurements and integrate these devices into lighting control systems. This, however, can result in new issues such as privacy controversies and high computational costs, induced by high spatial resolutions. Therefore, this study aims to propose a spatial resolution that is able to measure the luminance accurately while minimizing privacy sensitivity and computational costs. This is done based on luminance distribution measurements in office environments. The accuracy of lower resolution luminance distributions is tested for the mean and maximum luminance and the illuminance. Additionally, the ability to recognize faces is measured as an indicator for privacy-sensitive content. Finally, the processing time is measured as an indicator for the computational costs. The results show that for mean luminance or illuminance measurements the spatial resolution can be reduced significantly to 440 x 330 and 720 x 540 pixels, respectively. This spatial resolution does not compromise the accuracy while minimizing the ability of automated facial recognition and reducing the computational costs significantly. However, for maximum luminance measurements, a high resolution of 3000 x 2250 pixels is deemed appropriate, although this does allow automated facial recognition and results in high computation costs. A toolbox has been developed to assist others in choosing a relevant spatial resolution for their luminance camera during long term luminance measurements in typical office environments

Feasibility of ceiling-based luminance distribution measurements

There is a high relevancy in the luminance distribution related to the perceived visual comfort. Moreover, the required technology is maturing such that it is feasible to integrate such devices in lighting control systems, which is expected to improve the overall lighting quality in office environments, or to conduct long-term field studies. Preferably, the luminance distribution measurement corresponds to the visual field of the user. However, for long-term measurements this is not feasible as this causes interference. Therefore, this study aimed to find a suitable ceiling-based position for luminance distribution measurements. In a first phase, the most suitable ceiling-based measurement position was identified for four luminance based metrics: Desktop Luminance, Monitor Luminance, B40 Luminance, and Retinal Illuminance. The results showed that a ceiling-based position above the aisle with a 20° angle relative to the ceiling was the most suitable position because its field of view has large similarities with the field and angle of view of the user. In a second phase, the performance of this most suitable position found in phase 1 was assessed under real office conditions, and compared with the visual field of the user. The Desktop and Monitor Luminance achieved an acceptable accuracy with very basic commissioning. The Retinal illuminance was measured with a reasonable accuracy when an elaborate calibration procedure was applied. For the B40 Luminance, in all scenarios, inaccuracies above 20% were found. This study shows that ceiling-based measurements are feasible, except for the B40 luminance, however, one should account for the introduced uncertainty

How not to become a buffoon in front of a shop window: a solution allowing natural head movement for interaction with a public display

The user interaction solution described in this paper was developed in the context of an Intelligent Shop Window (ISW) with an aim to offer a user the interaction solution where system response would be triggered by naturally gazing at products. We have analyzed a possibility to realize such a user interaction solution using gaze tracking and concluded that remote calibration free eye tracking is still a subject of academic research, but that head tracking could be used instead. We argue that conventional use of head tracking requires conscious intentional head movements and thus does not fit into the context of applications such as the ISW. We further describe our experiment aimed to explore how head movements relate to eye movements when looking at objects in a shop window context. We show large variability in head movement and that per individual the gaze-head data could well be approximated with a straight line. Based on these results we propose a new solution that enables natural gaze interaction by means of head tracking

Influence of wall luminance and uniformity on preferred task illuminance

Literature suggests an influence of the luminance from non-horizontal surfaces in our visual field on our visual and psychological assessments of an office space. These assessments are believed to directly relate to our expressed preferred task illuminances.\u3cbr/\u3eThis paper describes an evaluation in a mock-up office, wherein wall conditions with a non-uniform and a more uniform light distribution of 3 different average luminance levels have been evaluated regarding their effect on users' preferred task illuminance. Each condition is evaluated starting from three different initial desk illuminances.\u3cbr/\u3eFor all test conditions, a wall with a non-uniformly distributed average luminance of 200 cd/m2 lead to significantly lower selected desk illuminances than a uniformly lit wall with the same average luminance level. In all cases, preferred task illuminances set were significantly lower when offering the lowest starting level for dimming of 300 lx. The range of preferred illuminance levels between subjects was also found to be smaller for dimming with the starting level of 300 lx at desk level.\u3cbr/\u3eThe study suggests that when providing users with personal control they will control the total perceived brightness in their visual field, even though they are only directly affecting their task illuminance level. Triggering the selection of lower preferred illuminance levels due to a personal control starting level of 300 lx, will positively influence the energy used for lighting. The smaller range of\u3cbr/\u3epreferred illuminance levels between subjects at the starting of 300 lx could reduce the risk of lighting preference related conflict between people. However, more research is needed to confirm that these smaller differences are also perceivable by users

Method of controlling an apparatus

The invention relates to an apparatus comprising user operable control means for controlling the apparatus, detection means for detecting an object and determining an identity of said object, and associating means for associating control options with said identity, the control means being operable to apply said control options in response to the detection means detecting and identifying said object