Prospectus, January 17, 2001

https://spark.parkland.edu/prospectus_2001/1001/thumbnail.jp

Evaluation and comparison of protein ultrafiltration test results: dead-end stirred cell compared with a cross-flow system

Dead-end stirred cell devices are commonly used in laboratories to characterise ultrafiltration membranes and their separation behaviour. Additionally, protein separation data from such systems are used for process scale-up. Such devices are operated under conditions that are inherently different from those used during the continuous or semi-continuous processing of industrial feed streams. The work presented in this paper compares the rejection behaviour of single protein solutions in both a dead-end stirred cell (SC) device with that for a crossflow system (CF). The effect of ionic strength (20 mM and 100 mM) and solution pH (4.9, 6.0, 7.1, 8.4 and 11.0) on protein filtration (bovine serum albumin (BSA) and lysozyme (LYZ) from buffered aqueous solutions) behaviour has been investigated using polyethersulfone (PES) membranes with a manufacturer specified molecular weight cut-off (MWCO) of 50 kDa. PES membranes were characterised in terms of dextran MWCO using both the SC and the CF systems. The mode of operation resulted in significant observed differences in the resulting dextran solute rejection curves for the two systems. The observed rejection (Robs) values for a series of dextran standards were consistently found to be lower for the CF system compared with the SC unit suggesting higher wall concentrations (Cw) due to concentration polarisation effects in the CF unit. Protein ultrafiltration studies with the 50 kDa PES membranes highlighted important differences in observed protein rejection behaviour despite operation of the two systems at the same transmembrane pressures (25 kPa). Solution pH was found to have little effect on the rejection of both BSA and LYZ. The solute rejection was found to be more sensitive to ionic strength effects for the SC device both during BSA and LYZ filtration. Convective mass transfer coefficients and hence the true rejection coefficients (Rtr) were calculated for both systems using the stagnant film model to understand the influence of hydrodynamic effects on the ultrafiltration behaviour of the two systems. The magnitude of the Peclet number (Pe) provides a means of comparing hydrodynamic conditions for the two systems and thereby allows differences in observed solute rejection to be better understood

Prospectus, February 7, 2001

https://spark.parkland.edu/prospectus_2001/1004/thumbnail.jp

Tutors and gatekeepers in sustainability MOOCS

Purpose The purpose of this paper is to explore the nature of interactions between learners in a massive open online course (MOOC), particularly role of the tutors in such interactions. For educators concerned with sustainability literacy, the authors are necessarily both affected by, and effectors of, digital pedagogies. The call for papers for this special issue challenged the authors to consider whether digital pedagogies are “supportive of sustainability or perpetuators of unsustainability”. As might be expected, this question is not a simple binary choice and the authors have chosen to address it indirectly, by considering the nature of interaction in a global, digitally connected community of learners. In particular, the changing role of tutors in these communities, and the possible implications of this change on sustainable literacy, are examined. Design/methodology/approach The authors focus on the “Sustainability for Professionals” massive open online course (MOOC) delivered by the University of Bath on the FutureLearn platform which hosts the “Inside Cancer” MOOC, also from Bath. “Sustainability for Professionals” is pedagogically connectivist, with “Inside Cancer” being more traditional and instructor led. The authors used social network analysis (SNA) for the research. It is a key tool to understand interactions in an online environment and allows quantitative comparison between different networks and thus between courses. In the context of digital pedagogy, the authors used a number of relevant SNA metrics to carry out analysis of MOOC network structures. Findings It was found that MOOCs are different in their network structure but tend to adapt to the subject matter. Digital pedagogies for sustainability result in a qualitative as well as quantitative change in learning where course design affects the learning process and gatekeepers are critical for information flow. These gatekeepers are distinct from tutors in the network. In such a network, tutors’ role is limited to course delivery and verifying, depending on course content, the information within the network. The analysis shows that network learning is dependent on course design and content, and gatekeepers exercise influence over the information within the network. Originality/value This study has implications for sustainability literacy. The authors examined the extent to which patterns of interaction in the network affect the learning process, and how this can help participants engage with the concept of sustainability. They used SNA to explore the nature of interaction between learners in a MOOC, particularly the role of the tutors in mediating such interactions. They also found that tutors can and do take a central role in early runs of the MOOC; however, with the subsequent runs, the removal of tutor nodes has little effect, suggesting that different modes of learning driven by participants are possible in a MOOC community. </jats:sec

Prospectus, March 7, 2001

https://spark.parkland.edu/prospectus_2001/1008/thumbnail.jp

A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach.

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10⁻⁷), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10⁻⁸). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10⁻¹⁵; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS

Common coding variant in SERPINA1 increases the risk for large artery stroke

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis