Design and User Satisfaction of Interactive Maps for Visually Impaired People

Multimodal interactive maps are a solution for presenting spatial information to visually impaired people. In this paper, we present an interactive multimodal map prototype that is based on a tactile paper map, a multi-touch screen and audio output. We first describe the different steps for designing an interactive map: drawing and printing the tactile paper map, choice of multi-touch technology, interaction technologies and the software architecture. Then we describe the method used to assess user satisfaction. We provide data showing that an interactive map - although based on a unique, elementary, double tap interaction - has been met with a high level of user satisfaction. Interestingly, satisfaction is independent of a user's age, previous visual experience or Braille experience. This prototype will be used as a platform to design advanced interactions for spatial learning

Production of mycobacterial cell wall glycopeptidolipids requires a member of the MbtH-like protein family

Background Glycopeptidolipids (GPLs) are among the major free glycolipid components of the outer membrane of several saprophytic and clinically-relevant Mycobacterium species. The architecture of GPLs is based on a constant tripeptide-amino alcohol core of nonribosomal peptide synthetase origin that is N-acylated with a 3-hydroxy/methoxy acyl chain synthesized by a polyketide synthase and further decorated with variable glycosylation patterns built from methylated and acetylated sugars. GPLs have been implicated in many aspects of mycobacterial biology, thus highlighting the significance of gaining an understanding of their biosynthesis. Our bioinformatics analysis revealed that every GPL biosynthetic gene cluster known to date contains a gene (referred herein to as gplH) encoding a member of the MbtH-like protein family. Herein, we sought to conclusively establish whether gplH was required for GPL production. Results Deletion of gplH, a gene clustered with nonribosomal peptide synthetase-encoding genes in the GPL biosynthetic gene cluster of Mycobacterium smegmatis, produced a GPL deficient mutant. Transformation of this mutant with a plasmid expressing gplH restored GPL production. Complementation was also achieved by plasmid-based constitutive expression of mbtH, a paralog of gplH found in the biosynthetic gene cluster for production of the siderophore mycobactin of M. smegmatis. Further characterization of the gplH mutant indicated that it also displayed atypical colony morphology, lack of sliding motility, altered capacity for biofilm formation, and increased drug susceptibility. Conclusions Herein, we provide evidence formally establishing that gplH is essential for GPL production in M. smegmatis. Inactivation of gplH also leads to a pleiotropic phenotype likely to arise from alterations in the cell envelope due to the lack of GPLs. While genes encoding MbtH-like proteins have been shown to be needed for production of siderophores and antibiotics, our study presents the first case of one such gene proven to be required for production of a cell wall component. Furthermore, our results provide the first example of a mbtH-like gene with confirmed functional role in a member of the Mycobacterium genus. Altogether, our findings demonstrate a critical role of gplH in mycobacterial biology and advance our understanding of the genetic requirements for the biosynthesis of an important group of constituents of the mycobacterial outer membrane

Endothelial-specific Nox2 overexpression increases vascular superoxide and macrophage recruitment in ApoE−/− mice

AIMS: Vascular disease states are associated with endothelial dysfunction and increased production of reactive oxygen species derived from NADPH oxidases. However, it remains unclear whether a primary increase in superoxide production specifically in the endothelium alters the initiation or progression of atherosclerosis. METHODS AND RESULTS: Mice overexpressing Nox2 specifically in the endothelium (Nox2-Tg) were crossed with ApoE(-/-) mice to produce Nox2-Tg ApoE(-/-) mice and ApoE(-/-) littermates. Endothelial overexpression of Nox2 in ApoE(-/-) mice did not alter blood pressure, but significantly increased vascular superoxide production compared with ApoE(-/-) littermates, measured using both lucigenin chemiluminescence and 2-hydroxyethidium production (ApoE(-/-), 19.9 ± 6.3 vs. Nox2-Tg ApoE(-/-), 47.0 ± 7.0 nmol 2-hydroxyethidium/aorta, P< 0.05). Increased endothelial superoxide production increased endothelial levels of vascular cell adhesion protein 1 and enhanced macrophage recruitment in early lesions in the aortic roots of 9-week-old mice, indicating increased atherosclerotic plaque initiation. However, endothelial-specific Nox2 overexpression did not alter native or angiotensin II-driven atherosclerosis in either the aortic root or the descending aorta. CONCLUSION: Endothelial-targeted Nox2 overexpression in ApoE(-/-) mice is sufficient to increase vascular superoxide production and increase macrophage recruitment possible via activation of endothelial cells. However, this initial increase in macrophage recruitment did not alter the progression of atherosclerosis. These results indicate that Nox-mediated reactive oxygen species signalling has important cell-specific and distinct temporal roles in the initiation and progression of atherosclerosis

SUMO chain formation is required for response to replication arrest in S. pombe

SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer

Operationalising learning from rare events: framework for middle humanitarian operations managers

The purpose of this paper is to investigate the learning from rare events and the knowledge management processinvolved, which presents a significant challenge to many organizations. This is primarily attributed to the inability tointerpret these events in a systematic and “rich” manner, which this paper seeks to address. We start by summarizing therelevant literature on humanitarian operations management (HOM), outlining the evolution of the socio-technical disasterlifecycle and its relationship with humanitarian operations, using a supply chain resilience theoretical lens. We then out-line theories of organizational learning (and unlearning) from disasters and the impact on humanitarian operations. Subse-quently, we theorize the role of middle managers in humanitarian operations, which is the main focus of our paper. Themain methodology incorporates a hybrid of two techniques for root cause analysis, applied to two related case studies.The cases were specifically selected as, despite occurring twenty years apart, there are many similarities in the chain ofcausation and supporting factors, potentially suggesting that adequate learning from experience and failures is not occur-ring. This provides a novel learning experience within the HOM paradigm. Hence, the proposed approach is based on amultilevel structure that facilitates the operationalization of learning from rare events in humanitarian operations. Theresults show that we are able to provide an environment for multiple interpretations and effective learning, with emphasison middle managers within a humanitarian operations and crisis/disaster management context

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Evaluation of vaccine delivery systems for inducing long-lived antibody responses to Dermanyssus gallinae antigen in laying hens

Dermanyssus gallinae, the poultry red mite, is a global threat to the commercial egg-laying industry. Control of D. gallinae is difficult, with only a limited number of effective pesticides and non-chemical treatments available. Here we characterise the candidate vaccine antigen D. gallinae cathepsin D-1 (Dg-CatD-1) and demonstrate that purified refolded recombinant Dg-Cat-D1 (rDg-CatD-1) is an active aspartyl proteinase which digests haemoglobin with a pH optimum of pH 4. Soluble protein extracts from D. gallinae also have haemoglobinase activity, with a pH optimum comparable to the recombinant protein and both proteinase activities were inhibited by the aspartyl proteinase inhibitor Pepstatin A. Enzyme activity and the ubiquitous localization of Dg-CatD-1 protein in sections of adult female mites is consistent with Dg-CatD-1 being a lysosomal proteinase. Using Dg-CatD-1 as a model vaccine antigen, we compared vaccine delivery methods in laying hens via vaccination with: i) purified rDg-CatD-1 with Montanide™ ISA 71 VG adjuvant; ii) recombinant DNA vaccines for expression of rDg-CatD-1 and iii) transgenic coccidial parasite Eimeria tenella expressing rDg-CatD-1. In two independent trials, only birds vaccinated with rDg-CatD-1 with Montanide™ ISA 71 VG produced a strong and long-lasting serum anti-rDg-Cat-D1 IgY response, which was significantly higher than control birds vaccinated with adjuvant only. Furthermore, we showed that egg laying rates of D. gallinae mites fed on birds vaccinated with rDg-CatD-1 in Montanide™ ISA 71 VG was reduced significantly compared with mites fed on unvaccinated birds