The Athabasca University edusource Project: Building An Accessible Learning Object Repository

Athabasca University - Canada's Open University (AU) made the commitment to put all of its courses online as part of its Strategic University Plan. In pursuit of this goal, AU participated in the eduSource project, a pan-Canadian effort to build the infrastructure for an interoperable network of learning object repositories. AU acted as a leader in the eduSource work package, responsible for the metadata and standards for learning objects. In addition, the team of professionals, academics, librarians and other researchers worked to create an accessible repository of learning objects across university departments and subjects. Most critically, the team worked beyond the development of a learning object repository and considered the adaptation of content and related applications, pedagogical approaches and the use of learning objects by instructional designers, faculty and the learners themselves. This paper describes one institution's approach to learning object repository development, from a technical and pedagogical perspective, along with some of the lessons learned during the process

UK Housing Market: Time Series Processes with Independent and Identically Distributed Residuals

The paper examines whether a univariate data generating process can be identified which explains the data by having residuals that are independent and identically distributed, as verified by the BDS test. The stationary first differenced natural log quarterly house price index is regressed, initially with a constant variance and then with a conditional variance. The only regression function that produces independent and identically distributed standardised residuals is a mean process based on a pure random walk format with Exponential GARCH in mean for the conditional variance. There is an indication of an asymmetric volatility feedback effect but higher frequency data is required to confirm this. There could be scope for forecasting the index but this is tempered by the reduction in the power of the BDS test if there is a non-linear conditional variance process

Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis.

BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two -871G and -336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens

Activism and Legitimation in Israel's Jurisprudence of Occupation

Colonial law need not exclude the colonized in order to subordinate them, and ‘activist’ courts can advance the effect of subordination no less than ‘passive’ courts. As a case study, this article examines the jurisprudential legacy of the Israeli Supreme Court in the context of the prolonged Israeli occupation of Palestine. Applying insights from legal realist, law and society, and critical legal studies scholarship, the article questions the utility of using the activist and passive labels. It illustrates how the Israeli activist court, through multiple legal and discursive moves, has advanced and legitimated the colonization of Palestine; that the court is aware of its role; and that arguments that focus on the court’s informal role do not mitigate this legitimating effect. Unlike other scholars, the article shows that the Israeli court’s role—by extending the power of judicial review to the military’s actions in the occupied areas—is neither novel nor unique or benevolent, as the British colonization of India and the US colonization of Puerto Rico show

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation

Assessing sustainability in housing LED urban regeneration : insights from a housing association in Northern England

How far do current assessment methods allow the thorough evaluation of sustainable urban regeneration? Would it be useful, to approach the evaluation of the environmental and social impacts of housing regeneration schemes, by making both hidden pitfalls and potentials explicit, and budgeting costs and benefits in the stakeholders’ perspective? The paper aims at answering these questions, by focusing on a case study located in the Manchester area, the City West Housing Trust, a nonprofit housing association. Drawing from extensive fieldwork and including several interviews with key experts from this housing association, the paper first attempts to monetize the environmental and social value of two extant projects – a high-rise housing estate and an environmentally-led program. It then discusses whether and how a stakeholder-oriented approach would allow more engagement of both current and potential funders in the projects at hand. Findings from both the literature and the empirical data that was gathered show how in current housing regeneration processes, room for significant improvements in terms of assessment methods still exist. Findings additionally show that the environmental and social spillovers are largely disregarded because of a gap in the evaluation tools. This may also hinder the potential contributions of further funders in the achievements of higher impacts in terms of sustainability

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages

notes: PMCID: PMC4006850types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov'tCandida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine), differentiation (M1-/M2-type) or activation status (vitamin D3 stimulation). We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore, protein mannosylation may play a key role in alterations of phagosomal properties caused by C. glabrata.Deutsche ForschungsgemeinschaftNational Institutes for HealthWellcome TrustBBSR

The Dectin-2 family of C-type lectin-like receptors : an update

Peer reviewedPublisher PD