Rheumatoid arthritis sera react with a phage-displayed peptide selected by a monoclonal antibody to type II collagen that has homology to EBNA-1

Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies involving probing of phage-displayed random peptide libraries with an antibody to type II collagen, CII-C1, we observed that among 17 phagotopes selected 5 expressed peptides with homology with the sequence of EBNA-1. The residues in common were RLPFG. Hence we tested sera from 50 patients with RA, of whom 26 had antibodies to native type II collagen, and 43 healthy controls, for reactivity by ELISA with a phagotope selected 4 times, which expressed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted with the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with which reactivity occurred in 78% of RA patients and 81% of controls. Evidence for molecular mimicry was not found insofar as the phagotope did not inhibit reactivity of RA sera with EBNA-1 and CII-C1 was not reactive with EBNA-1. We conclude that the reactivity of the RA sera with the phagotope is most likely due to the phagotope being a mimic of an epitope of type II collagen for a proportion of RA sera.

Enriching architectural design education through interactive displays and local community engagement

Designers have a social responsibility to deal with the needs, issues, and problems that their clients and communities are confronted with. Students of design require opportunities to reflect on their role as social facilitators to develop an attitude towards community engagement through different phases and aspects of their careers. However, current design courses are challenged by compressed timeframes and fragmented scenarios of different academic requirements that do not actively teach community engagement. This paper outlines a participatory and technological approach that was employed to address these issues within the teaching of Architecture and Urban Design at the Queensland University of Technology, Brisbane, Australia. A multi-phase community based research project with actual stakeholders was implemented over a two-year period. Approximately 150 students in the final year of the Bachelor of Design-Architecture; 10 students in the Master of Architecture and 15 students in the Master of Design-Urban Design have informed and influenced each others’ learning through the teaching and research nexus facilitated by this project. The technical approach was implemented in form of a bespoke digital platform that supported the display and discussion of digital media on a series of interactive touch walls. The platform allowed students to easily upload their final designs onto large interactive surfaces, where visitors could explore the media and provide comments. Through the use of this technical platform and the introduction of neogeography, students have been able to broaden their level of interaction and support their learning experience through external structured and unstructured feedback from the local community. Students have not only been exposed to community representatives, but they also have been working in parallel on a specific case study providing each other, across different years and courses, material for reflection and data to structure their design activities.

Introduction to "Learning Chinese as a Heritage Language : An Australia Perspective"

The book grapples with the complex entanglement of identity construction, language choice, cultural heritage, and social orders. Specifically, the book investigates how Chinese Australians negotiate their Chineseness and capitalise on resources through learning Chinese as a heritage language in Australia and beyond. Though the book is concerned with Chinese Australians, knowledge built and lessons learned can provide insight into other multicultural settings where people of Chinese descent are becoming increasingly prominent in representing the cultural and linguistic diversity of the society, and more recently, in contributing to the economic dynamics of the society. In addition, the focus on the potholes and distractions as well as the benefits and gains of heritage language learning is not restricted to Chinese diaspora, but relevant to ethnic minority individuals and communities elsewhere.

Manufacturing and use of human placenta-derived mesenchymal stromal cells for phase I clinical trials: Establishment and evaluation of a protocol

Background/Aim. Mesenchymal stromal cells (MSCs) have been utilised in many clinical trials as an experimental treatment in numerous clinical settings. Bone marrow remains the traditional source tissue for MSCs but is relatively hard to access in large volumes. Alternatively, MSCs may be derived from other tissues including the placenta and adipose tissue. In an initial study no obvious differences in parameters such as cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability, were detected when we compared human marrow derived- MSCs to human placenta-derived MSCs. The aim of this study was to establish and evaluate a protocol and related processes for preparation placenta-derived MSCs for early phase clinical trials. Methods. A full-term placenta was taken after delivery of the baby as a source of MSCs. Isolation, seeding, incubation, cryopreservation of human placentaderived MSCs and used production release criteria were in accordance with the complex regulatory requirements applicable to Code of Good Manufacturing Practice manufacturing of ex vivo expanded cells. Results. We established and evaluated instructions for MSCs preparation protocol and gave an overview of the three clinical areas application. In the first trial, MSCs were co-transplanted iv to patient receiving an allogeneic cord blood transplant as therapy for treatmentrefractory acute myeloid leukemia. In the second trial, MSCs were administered iv in the treatment of idiopathic pulmonary fibrosis and without serious adverse effects. In the third trial, MSCs were injected directly into the site of tendon damage using ultrasound guidance in the treatment of chronic refractory tendinopathy. Conclusion. Clinical trials using both allogeneic and autologous cells demonstrated MSCs to be safe. A described protocol for human placenta-derived MSCs is appropriate for use in a clinical setting, relatively inexpensive and can be relatively easily adjusted to a different set of regulatory requirements, as applicable to early phase clinical trials.

Multifunctional three-dimensional T-junction graphene micro-wells: Energy-efficient, plasma-enabled growth and instant water-based transfer for flexible device applications

The “third-generation” 3D graphene structures, T-junction graphene micro-wells (T-GMWs) are produced on cheap polycrystalline Cu foils in a single-step, low-temperature (270 °C), energy-efficient, and environment-friendly dry plasma-enabled process. T-GMWs comprise vertical graphene (VG) petal-like sheets that seemlessly integrate with each other and the underlying horizontal graphene sheets by forming T-junctions. The microwells have the pico-to-femto-liter storage capacity and precipitate compartmentalized PBS crystals. The T-GMW films are transferred from the Cu substrates, without damage to the both, in de-ionized or tap water, at room temperature, and without commonly used sacrificial materials or hazardous chemicals. The Cu substrates are then re-used to produce similar-quality T-GMWs after a simple plasma conditioning. The isolated T-GMW films are transferred to diverse substrates and devices and show remarkable recovery of their electrical, optical, and hazardous NO2 gas sensing properties upon repeated bending (down to 1 mm radius) and release of flexible trasparent display plastic substrates. The plasma-enabled mechanism of T-GMW isolation in water is proposed and supported by the Cu plasma surface modification analysis. Our GMWs are suitable for various optoelectronic, sesning, energy, and biomedical applications while the growth approach is potentially scalable for future pilot-scale industrial production.

Alteration of the C-terminal ligand specificity of the Erbin PDZ domain by allosteric mutational effects

Modulation of protein binding specificity is important for basic biology and for applied science. Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus. Our goal was to engineer variants of the Erbin PDZ domain with altered specificity for the most C-terminal position (position 0) where a Val is strongly preferred by the wild-type domain. We constructed a library of PDZ domains by randomizing residues in direct contact with position 0 and in a loop that is close to but does not contact position 0. We used phage display to select for PDZ variants that bind to 19 peptide ligands differing only at position 0. To verify that each obtained PDZ domain exhibited the correct binding specificity, we selected peptide ligands for each domain. Despite intensive efforts, we were only able to evolve Erbin PDZ domain variants with selectivity for the aliphatic C-terminal side chains Val, Ile and Leu. Interestingly, many PDZ domains with these three distinct specificities contained identical amino acids at positions that directly contact position 0 but differed in the loop that does not contact position 0. Computational modeling of the selected PDZ domains shows how slight conformational changes in the loop region propagate to the binding site and result in different binding specificities. Our results demonstrate that second-sphere residues could be crucial in determining protein binding specificity.

Situated interfaces for engaging citizens on the go

Insights Live screening and playfulness of the interactive space can be effective strategies for attracting the attention of passers-by and turn them into active participants. While urban screen interfaces increase participation by encouraging group interaction, privately-oriented tangible user interfaces give people a longer time to reflect upon their answers.

Current management of transitional feeding issues in preterm neonates born in Queensland, Australia

Background: Many preterm neonates display difficulty establishing suck-feeding competence in the weeks following birth. Ineffective management of transitional feeding issues may cause patient complications, and can contribute to increased length of stay. Aims: Given that many neonatal nurseries appear to vary in their neonatal feeding management practices, the aim of this study was to investigate and document the routine level of support and intervention currently provided for preterm neonates with transitional feeding issues across the various level II (special care) nurseries (SCNs) in Queensland, Australia. Methods: A questionnaire was mailed to all Queensland SCNs in 2005 (n = 36). The questionnaire contained a series of closed-choice and short-answer questions designed to obtain information from each SCN regarding their current practices for managing transitional feeding issues in preterm neonates. Results were confirmed during a follow-up phone call. Results: Responses were obtained from 29 SCNs (80.6%). None of these nurseries reported having any formal, written policies regarding the management of transitional feeding issues in preterm neonates. Wide variations were reported in relation to the suck-feeding assessments and interventions used by staff within the various SCNs. Of the 29 nurseries, 4 (13.8%) reported using checklists or assessments to judge readiness for suck-feeds, and 5 (17.2%) reported using pulse oximetry to judge tolerance of suck-feeding attempts. Eighteen SCNs (62.1%) reported offering some form of active intervention to assist neonates with transitional feeding issues, with the most common intervention techniques reported being non-nutritive sucking during tube feeds, pre-feeding oral stimulation, and actively pacing suck-feeds. Twenty-two SCNs (75.4%) reported having access to a lactation consultant to assist mothers with breastfeeding issues. Conclusions: Differences were reported in the routine management of transitional feeding issues in preterm neonates across the various SCNs in Queensland. It is suggested that evidence based guidelines need to be developed, and that, in order to do this, further research studies are required to determine current best practice, as well as to answer remaining questions. © 2008 Elsevier Ireland Ltd. All rights reserved.

Growth patterns in preterm infants born appropriate for gestational age

Aim: This study aimed to document the growth patterns of a contemporary cohort of preterm infants born appropriate for gestational age (AGA). It was hypothesised that preterm AGA (PT-AGA) infants would display poorer growth than full-term AGA (FT-AGA) infants. Methods: Sixty-four PT-AGA infants and 64 FT-AGA infants were assessed at 0, 4, 8 and 12 months of corrected age (CA). Measurements of weight and length were recorded at each of the specified ages. Centers for Disease Control and Prevention growth data were used to calculate Z-scores for weight and length based on CA. Results: The mean length and weight Z-scores of PT-AGA infants were found to be significantly less than those of FT-AGA infants at term, 4, 8 and 12 months of CA (P < 0.001). The mean weight Z-score of PT-AGA infants was found to be less than their mean length Z-score at each time point, though the differences were not significant. Conclusions: The results of this study suggest that PT-AGA infants are likely to display poorer growth than FT-AGA infants until at least 1 year of CA. Long-term growth monitoring in this population is recommended. © 2008 The Authors.

Understanding file access mechanisms for embedded ubicomp collaboration interfaces

This paper explores the nature of interfaces to support people in accessing their files at tabletop displays embedded in the environment. To do this, we designed a study comparing people's interaction with two very different classes of file system access interface: Focus, explicitly designed for tabletops, and the familiar hierarchical Windows Explorer. In our within-subjects double-crossover study, participants collaborated on 4 planning tasks. Based on video, logs, questionnaires and interviews, we conclude that both classes of interface have a place. Notably, Focus contributed to improved collaboration and more efficient use of the workspace than with Explorer. Our results inform a set of recommendations for future interfaces enabling this important class of interaction -- supporting access to files for collaboration at tabletop devices embedded in an ubicomp environment.

Biceps femoris architecture and strength in athletes with a prior ACL reconstruction

Purpose To determine if limbs with a history of anterior cruciate ligament (ACL) injury reconstructed from the semitendinosus (ST) display different biceps femoris long head (BFlh) architecture and eccentric strength, assessed during the Nordic hamstring exercise, compared to the contralateral uninjured limb. Methods The architectural characteristics of the BFlh were assessed at rest and at 25% of a maximal voluntary isometric contraction (MVIC) in the control (n=52) and previous ACL injury group (n=15) using two-dimensional ultrasonography. Eccentric knee-flexor strength was assessed during the Nordic hamstring exercise. Results Fascicle length was shorter (p=0.001; d range: 0.90 to 1.31) and pennation angle (p range: 0.001 to 0.006: d range: 0.87 to 0.93) was greater in the BFlh of the ACL injured limb when compared to the contralateral uninjured limb at rest and during 25% of MVIC. Eccentric strength was significantly lower in the ACL injured limb than the contralateral uninjured limb (-13.7%; -42.9N; 95% CI = -78.7 to -7.2; p=0.021; d=0.51). Fascicle length, MVIC and eccentric strength were not different between the left and right limb in the control group. Conclusions Limbs with a history of ACL injury reconstructed from the ST have shorter fascicles and greater pennation angles in the BFlh compared to the contralateral uninjured side. Eccentric strength during the Nordic hamstring exercise of the ACL injured limb is significantly lower than the contralateral side. These findings have implications for ACL rehabilitation and hamstring injury prevention practices which should consider altered architectural characteristics.

Some remarks on the symplectic pairing on the moduli space of representations of the fundamental group of surfaces

This work grew out of an attempt to understand a conjectural remark made by Professor Kyoji Saito to the author about a possible link between the Fox-calculus description of the symplectic structure on the moduli space of representations of the fundamental group of surfaces into a Lie group and pairs of mutually dual sets of generators of the fundamental group. In fact in his paper [3] , Prof. Kyoji Saito gives an explicit description of the system of dual generators of the fundamental group.

BPMN process views construction

Process view technology is catching more attentions in modern business process management, as it enables the customisation of business process representation. This capability helps improve the privacy protection, authority control, flexible display, etc., in business process modelling. One of approaches to generate process views is to allow users to construct an aggregate on their underlying processes. However, most aggregation approaches stick to a strong assumption that business processes are always well-structured, which is over strict to BPMN. Aiming to build process views for non-well-structured BPMN processes, this paper investigates the characteristics of BPMN structures, tasks, events, gateways, etc., and proposes a formal process view aggregation approach to facilitate BPMN process view creation. A set of consistency rules and construction rules are defined to regulate the aggregation and guarantee the order preservation, structural and behaviour correctness and a novel aggregation technique, called EP-Fragment, is developed to tackle non-well-structured BPMN processes.

Synthesis, X-ray structures, and spectroscopic and electrochemical properties of (mu-oxo)bis(mu-carboxylato)diruthenium complexes having six imidazole bases as terminal ligands

Complexes [Ru2O(O2CR)(2)(1-MeIm)(6)](ClO4)(2) (la-c), [Ru2O(O2CR)(2)(ImH)(6)](ClO4)(2) (2a,b), and [Ru2O(O2CR)(2)(4-MeImH)(6)](ClO4)(2) (3a,b) with a (mu-oxo)bis(mu-carboxylato)diruthenium(III) core have been prepared by reacting Ru2Cl(O2CR)(4) with the corresponding imidazole base, viz. 1-methylimidazole (1-MeIm), imidazole (ImH), and 4-methylimidazole (4-MeImH) in methanol, followed by treatment with NaClO4 in water (R: Me, a; C6H4-p-OMe, b; C6H4-p-Me, c). Diruthenium(III,IV) complexes [Ru2O(O2CR)(2)(1-MeIm)(6)](ClO4)(3) (R: Me, 4a; C6H4-p-OMe, 4b; C6H4-p-Me, 4c) have been prepared by one-electron oxidation of 1 in MeCN with K2S2O8 in water. Complexes la, 2a . 3H(2)O, and 4a . 1.5H(2)O have been structurally characterized. Crystal data for the complexes are as follows: la, orthorhombic, P2(1)2(1)2(1), a = 7.659(3) Angstrom, b = 22.366(3) Angstrom, c = 23.688(2) Angstrom, V = 4058(2) Angstrom(3), Z = 4, R = 0.0475, and R-w = 0.0467 for 2669 reflections with F-o > 2 sigma(F-o); 2a . 3H(2)O, triclinic, , a = 13.735(3) Angstrom, b = 14.428(4) Angstrom, c = 20.515(8) Angstrom, alpha = 87.13(3)degrees, beta = 87.61(3)degrees, gamma = 63.92(2)degrees, V = 3646(2) Angstrom(3), Z = 4, R = 0.0485 and R-w = 0.0583 for 10 594 reflections with F-o > 6 sigma(F-o); 4a . 1.5H(2)O triclinic, , a = 11.969(3) Angstrom, b = 12.090(6) Angstrom, c = 17.421(3) Angstrom, alpha = 108.93(2)degrees, beta = 84.42(2)degrees, gamma = 105.97(2)degrees, V = 2292(1) Angstrom(3), Z = 2, R = 0.0567, and R-w = 0.0705 for 6775 reflections with F-o > 6 sigma(F-o). The complexes have a diruthenium unit held by an oxo and two carboxylate ligands, and the imidazole ligands occupy the terminal sites of the core. The Ru-Ru distance and the Ru-O-oxo-Ru angle in la and 2a . 3H(2)O are 3.266(1), 3.272(1) Angstrom and 122.4(4), 120.5(2)degrees, while in 4a . 1.5H(2)O these values are 3.327(1) Angstrom and 133.6(2)degrees. The diruthenium(III) complexes 1-3 are blue in color and they exhibit an intense visible band in the range 560-575 nm. The absorption is charge transfer in nature involving the Ru(III)-d pi and O-oxo-p pi orbitals. The diruthenium(III,IV) complexes are red in color and show an intense band near 500 nm. The diruthenium(III) core readily gets oxidized with K2S2O8 forming quantitatively the diruthenium(III,IV) complex. The visible spectral record of the conversion shows an isosbestic point at 545 nm for 1 and at 535 nm for 2 and 3. Protonation of the oxide bridge by HClO4 in methanol yields the [Ru-2(mu-OH)(mu-O2CR)(2)](3+) core. The hydroxo species shows a visible band al 550 nm. The pK(a) value for la is 2.45. The protonated species are unstable. The 1-MeIm species converts to the diruthenium(III,IV) core, while the imidazole complex converts to [Ru(ImH)(6)](3+) and some uncharacterized products. Complex [Ru(ImH)(6)](ClO4)(3) has been structurally characterized. The diruthenium(III) complexes are essentially diamagnetic and show characteristic H-1 NMR spectra indicating the presence of the dimeric structure in solution. The diruthenium(III,IV) complexes are paramagnetic and display rhombic EPR spectral features. Complexes 1-3 are redox active. Complex 1 shows the one-electron reversible Ru-2(III)/(RuRuIV)-Ru-III, one-electron quasireversible (RuRuIV)-Ru-III/Ru-2(IV), and two-electron quasireversible Ru-2(III)/Ru-2(II) couples near 0.4, 1.5, and -1.0 V vs SCE In MeCN-0.1 M TBAP, respectively, in the cyclic and differential pulse voltammetric studies. Complexes 2 and 3 exhibit only reversible Ru-2(III)/(RuRuIV)-Ru-III and the quasireversible (RuRuIV)-Ru-III/Ru-2(IV) couples near 0.4 and 1.6 V vs SCE, respectively, The observation of a quasireversible one-step two-electron transfer reduction process in 1 is significant considering its relevance to the rapid and reversible Fe-2(III)/Fe-2(II) redox process known for the tribridged diiron core in the oxy and deoxy forms of hemerythrin.

Topological mimicry and epitope duplication in the guanylyl cyclase C receptor

Guanylyl cyclase C (GCC) is the receptor for the gastrointestinal hormones, guanylin, and uroguanylin, in addition to the bacterial heat-stable enterotoxins, which are one of the major causes of watery diarrhea the world over. GCC is expressed in intestinal cells, colorectal tumor tissue and tumors originating from metastasis of the colorectal carcinoma. We have earlier generated a monoclonal antibody to human GCC, GCC:B10, which was useful for the immunohistochemical localization of the receptor in the rat intestine (Nandi A et al., 1997, J Cell Biochem 66:500-511), and identified its epitope to a 63-amino acid stretch in the intracellular domain of GCC. In view of the potential that this antibody has for the identification of colorectal tumors, we have characterized the epitope for GCC:B10 in this study. Overlapping peptide synthesis indicated that the epitope was contained in the sequence HIPPENIFPLE. This sequence was unique to GCC, and despite a short stretch of homology with serum amyloid protein and pertussis toxin, no cross reactivity was detected. The core epitope was delineated using a random hexameric phage display library, and two categories of sequences were identified, containing either a single, or two adjacent proline residues. No sequence identified by phage display was identical to the epitope present in GCC, indicating that phage sequences represented mimotopes of the native epitope. Alignment of these sequences with HIPPENIFPLE suggested duplication of the recognition motif, which was confirmed by peptide synthesis. These studies allowed us not only to define the requirements of epitope recognition by GCC:B10 monoclonal antibody, but also to describe a novel means of epitope recognition involving topological mimicry and probable duplication of the cognate epitope in the native guanylyl cyclase C receptor sequence.