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.

Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤0.05) at markers close to or within the candidate genes IL- 1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.

A novel approach to 6-DOF adaptive trajectory tracking control of an AUV in the presence of parameter uncertainties

In this paper, the trajectory tracking control of an autonomous underwater vehicle (AUVs) in six-degrees-of-freedom (6-DOFs) is addressed. It is assumed that the system parameters are unknown and the vehicle is underactuated. An adaptive controller is proposed, based on Lyapunov׳s direct method and the back-stepping technique, which interestingly guarantees robustness against parameter uncertainties. The desired trajectory can be any sufficiently smooth bounded curve parameterized by time even if consist of straight line. In contrast with the majority of research in this field, the likelihood of actuators׳ saturation is considered and another adaptive controller is designed to overcome this problem, in which control signals are bounded using saturation functions. The nonlinear adaptive control scheme yields asymptotic convergence of the vehicle to the reference trajectory, in the presence of parametric uncertainties. The stability of the presented control laws is proved in the sense of Lyapunov theory and Barbalat׳s lemma. Efficiency of presented controller using saturation functions is verified through comparing numerical simulations of both controllers.

Fabrication and characterization of RF plasma polymerized thin films from 3,7-dimethyl-1,6-octadien-3-ol for electronic and biomaterial applications

Poly(linalool) thin films were fabricated using RF plasma polymerisation. All films were found to be smooth, defect-free surfaces with average roughness of 0.44 nm. The FTIR analysis of the polymer showed a notable reduction in –OH moiety and complete dissociation of C=C unsaturation compared to the monomer, and presence of a ketone band absent from the spectrum of the monomer. Poly(linalool) were characterised by chain branching and a large quantity of short polymer chains. Films were optically transparent, with refractive index and extinction coefficient of 1.55 and 0.001 (at 500 nm) respectively, indicating a potential application as an encapsulating (protective) coating for circuit boards. The optical band gap was calculated to be 2.82 eV, which is in the semiconducting energy gap region.

Exploiting the beta distribution-based reputation model in recommender system

Reputation systems are employed to measure the quality of items on the Web. Incorporating accurate reputation scores in recommender systems is useful to provide more accurate recommendations as recommenders are agnostic to reputation. The ratings aggregation process is a vital component of a reputation system. Reputation models available do not consider statistical data in the rating aggregation process. This limitation can reduce the accuracy of generated reputation scores. In this paper, we propose a new reputation model that considers previously ignored statistical data. We compare our proposed model against state-of the-art models using top-N recommender system experiment.

Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Editorial of "International Journal of Critical Indigenous Studies, Volume 6, Number 1, 2013"

This edition of the International Journal of Critical Indigenous Studies marks the tenth since the journal’s launch in 2008. During that time, over forty articles and eleven book reviews have been published, which is testament to the continuing upward trajectory of Critical Indigenous Studies. Although there continues to be an increasing range of areas of Indigenous research to which a critical focus is brought to bear, a consistent issue for many of the journal’s contributors has been the delineation and application of Indigenous methods and methodologies in social research. The present edition is no exception, with two articles focussing on Indigenous-centred research. The first, by Krystal Summers, reflexively explores the author’s experiences as an undergraduate student undertaking Indigenous-centred research in Peru. As an Indigenous First Nations woman, Summers was mindful that her research practice was faithful to the ethics and protocols outlined in her original project proposal. Her subsequent ‘journey of critical reflexive understanding and storytelling’ supports the proposition of current literature in Indigenous research methodologies that a properly critical Indigenous ethnography will naturally enjoin with Indigenous epistemologies and methodologies.

Editorial of "International Journal of Critical Indigenous Studies Volume 6, Number 2, 2013"

The International Journal of Critical Indigenous Studies (IJCIS) now complements the recently launched National Indigenous Research and Knowledges Network (NIRAKN) in its efforts to build Indigenous research capacity. In this context the journal provides a platform for the research of Indigenous postgraduates, early- to mid-career researchers, and senior scholars. Indigenous scholars are therefore encouraged to submit their articles to future editions of the IJCIS, an ‘Excellence in Research for Australia’ (ERA) ranked journal.