Antibodies against human herpesvirus 8 in black South African patients with cancer

Background Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. Methods Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti–HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV-1 infection were examined with the use of unconditional logistic-regression models. Results Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti–HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti–HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1–positive patients than among those who were HIV-1–negative (P<0.001). Conclusions Among black patients with cancer in South Africa, the seroprevalence of anti–HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

Soft tissue human thigh and buttock finite element model to simulate vehicle seat cushion indentation

Accurate modelling of automotive occupant posture is strongly related to the mechanical interaction between human body soft tissue and flexible seat components. This paper presents a finite-element study simulating the deflection of seat cushion foam and supportive seat structures, as well as human buttock and thigh soft tissue when seated. The thigh-buttock surface shell model was based on 95th percentile male subject scan data and made of two layers, covering thin to moderate thigh and buttock proportions. To replicate the effects of skin and fat, the neoprene rubber layer was modelled as a hyperelastic material with viscoelastic behaviour. The analytical seat model is based on a Ford production seat. The result of the finite-element indentation simulation is compared to a previous simulation of an indentation with a hard shell human model of equal geometry, and to the physical indentation result. We conclude that SAE composite buttock form and human-seat indentation of a suspended seat cushion can be validly simulated.

Elucidating the host-pathogen interactions between in vitro human cells and enterovirus 71 in Hand, Foot and Mouth Disease (HFMD)

This study has provided further understanding of the pathogenesis of EV71, one of the major etiological agents associated with significant mortality in Hand, Foot and Mouth disease. Elucidating the host-pathogen interaction and the mechanism that the virus uses to bypass host defence systems to establish infection will aid in the development of potential antiviral therapeutics against EV71.

Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses

This is a comprehensive study of human kidney proximal tubular epithelial cells (PTEC) which are known to respond to and mediate the pathological process of a range of kidney diseases. It identifies various molecules expressed by PTEC and how these molecules participate in down-regulating the inflammatory process, thereby highlighting the clinical potential of these molecules to treat various kidney diseases. In the disease state, PTEC gain the ability to regulate the immune cell responses present within the interstitium. This down-regulation is a complex interaction of contact dependent/independent mechanisms involving various immuno-regulatory molecules including PD-L1, sHLA-G and IDO. The overall outcome of this down-regulation is suppressed DC maturation, decreased number of antibody producing B cells and low T cell responses. These manifestations within a clinical setting are expected to dampen the ongoing inflammation, preventing the damage caused to the kidney tissue.

Mobile interaction design approaches for reducing domestic food waste

This thesis is a trans-disciplinary study of domestic food waste in Australia. Firstly, it examines why consumers are prone to waste food. Secondly, it explores several situated design interventions to reduce domestic food waste by informing consumer food supply and location awareness, and improving the level of food literacy among consumers. The thesis outcomes have implications for academic and industry domains within the fields of Human-Computer Interaction, urban informatics, environmental sustainability, food security and public health.

Social interaction and the role of empathy in information and knowledge management

This article provides a general review of the literature on the nature and role of empathy in social interaction for information professionals working in a variety of information and knowledge environments. Relational agency theory (Edwards, 2005) is used asa framework to re-conceptualize education for empathic social interaction between information professionals and their clients. Past, present and future issues relevant to empathic interaction in information and knowledge management are discussed in the context of three shifts identified from the literature: (a) the continued increase in communication channels, both physical and virtual, for reference, information and re-search services, (b) the transition from the information age to the conceptual age and(c) the growing need for understanding of the affective paradigm in the information and knowledge professions. Findings from the literature review on the relationships between empathy and information behavior, social networking, knowledge management and information and knowledge services are presented. Findings are discussed in relation to the development of guidelines for the affective education and training of information and knowledge professionals and the potential use of virtual learning software such as Second Life in developing empathic communication skills

Temporal characteristics of melanopsin inputs to the human pupil light reflex

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

Teleoperation of a 7 DOF humanoid robot arm using human arm accelerations and EMG signals

We present our work on tele-operating a complex humanoid robot with the help of bio-signals collected from the operator. The frameworks (for robot vision, collision avoidance and machine learning), developed in our lab, allow for a safe interaction with the environment, when combined. This even works with noisy control signals, such as, the operator’s hand acceleration and their electromyography (EMG) signals. These bio-signals are used to execute equivalent actions (such as, reaching and grasping of objects) on the 7 DOF arm.

Design of a tablet sized human-computer interface and its effect on situation awareness

Emergency Response Teams increasingly use interactive technology to help manage information and communications. The challenge is to maintain a high situation awareness for different interactive devices sizes. This research specifically compared a handheld interactive device in the form of an iPad with a large interactive multi-touch tabletop. A search and rescue inspired simulator was designed to test operator situation awareness for the two sized devices. The results show that operators had better situation awareness on the tabletop device when the operation related to detecting of moving targets, searching target locations, distinguishing target types, and comprehending displayed information.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: Implications for xenograft models of human prostate cancer

Background Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. Methods An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. Results At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. Conclusion These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Growing food in the city: A study across interaction design and urban agriculture

The thesis offers the foundation of a design pattern language for urban gardening, as well as a prototype mobile storytelling platform through which urban gardeners can share gardening experiences. This study examined three urban agriculture communities – a city farm, a permaculture movement, and residential gardeners – in order to better understand some of the challenges in their food growing practices. The city is increasingly being rediscovered by gardeners, food activists, and local governments as an under-utilised opportunity space for land cultivation and local food production, and the findings of this research were analysed with a view to consider interactive technology and design interventions in response.

Interaction design for tablet based edutainment systems for mathematical education of primary student

Mathematics has been perceived as the core area of learning in most educational systems around the world including Sri Lanka. Unfortunately, it is clearly visible that a majority of Sri Lankan students are failing in their basic mathematics when the recent grade five scholarship examination and ordinary level exam marks are analysed. According to Department of Examinations Sri Lanka , on average, over 88 percent of the students are failing in the grade 5 scholarship examinations where mathematics plays a huge role while about 50 percent of the students fail in there ordinary level mathematics examination. Poor or lack of basic mathematics skills has been identified as the root cause.

Revisiting the Task-Capability interface model for incorporating human factors into car-following models

Human factors such as distraction, fatigue, alcohol and drug use are generally ignored in car-following (CF) models. Such ignorance overestimates driver capability and leads to most CF models’ inability in realistically explaining human driving behaviors. This paper proposes a novel car-following modeling framework by introducing the difficulty of driving task measured as the dynamic interaction between driving task demand and driver capability. Task difficulty is formulated based on the famous Task Capability Interface (TCI) model, which explains the motivations behind driver’s decision making. The proposed method is applied to enhance two popular CF models: Gipps’ model and IDM, and named as TDGipps and TDIDM respectively. The behavioral soundness of TDGipps and TDIDM are discussed and their stabilities are analyzed. Moreover, the enhanced models are calibrated with the vehicle trajectory data, and validated to explain both regular and human factor influenced CF behavior (which is distraction caused by hand-held mobile phone conversation in this paper). Both the models show better performance than their predecessors, especially in presence of human factors.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10-8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10-6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.