The call to retrieval: Kenneth Cragg's Christian vocation to Islam

The career of the Anglican scholar and bishop, Kenneth Cragg, focusses attention on the Christian understanding of other faiths in general and of Islam in particular. Cragg has been a leading exponent of a particular missionary approach to Islam, emphasizing that there is a 'mission to Islam' as much as a mission to Muslims. To this end he interprets Islam as pointing in its deepest meaning towards Christianity, a course which has aroused both admiration and opposition among Christians and Muslims alike. I attempt to show that his theology is strongly influenced by distinctive Anglican traditions, and nourished by one particular Arab Christian source. Cragg, however, resists any easy classification, and faces the accusation of theological evasiveness as well as hermeneutic sleight of hand. His writings show a remarkable consistency over thirty years and point to possibilities for reconciliation between deeply rooted religious antagonisms. A further significance of Cragg is his awareness of contemporary secularity in its interaction with and impact upon religious belief. Here again his conviction that the deepest convictions of unbelief are at heart religious needs to be tested. The central question is whether he illegitimately 'christianises' Islam, and by extension, other faiths and ideologies. His keyword is 'retrieval', but there are attitudes and beliefs that cannot be retrieved, only abandoned. Few would quarrel with the ethics he advocates, but the question remains whether his theological method can be accepted as valid

Investigation of GLUT4 sorting into the insulin responsive compartment: a role for ubiquitination and deubiquitination.

GLUT4 is the insulin-regulated glucose transporter found in muscle and adipose tissue. On insulin stimulation, GLUT4 translocates from a slowly recycling storage compartment (GLUT4 storage vesicles or GSVs) to the plasma membrane. This allows glucose to enter cells by diffusion down its concentration gradient, clearing glucose from the plasma. This response is defective in the disease states of insulin resistance and type 2 diabetes. The aim of this study is to understand how GLUT4 enters GSVs, which will hopefully extend our knowledge of insulin responsive tissues. Previous studies from our lab, expressing GLUT4 in yeast, have shown that GLUT4 is subject to the same nitrogen- and ubiquitin-dependent trafficking as the yeast amino acid permease Gap1p. In my thesis I have extended these studies into 3T3-L1 adipocytes, and shown that GLUT4 is ubiquitinated in this insulin responsive cell line. A ubiquitin resistant version of GLUT4 (HA-GLUT4 7K/R) has an impaired ability to enter GSVs and does not translocate in response to insulin. However GLUT4 mutants with single ubiquitination sites outwith the large intracellular loop are ubiquitinated and traffic in an identical manner to wild type GLUT4, addressing concerns that mutation of the large intracellular loop of GLUT4 in HA-GLUT4 7K/R affects its trafficking. The GGA family of clathrin adaptor proteins have previously been implicated in sorting of newly synthesised GLUT4 into GSVs. Our lab has shown previously that the two yeast Ggas are required for ubiquitin dependent trafficking of GLUT4 in yeast, as is the case for Gap1p. I have gone on to show that the ubiquitin binding function of the GGA3 GAT domain is, at least partially, required for an in vitro interaction between GLUT4 and the VHS-GAT domains of GGA3. When expressed in adipocytes, a ubiquitin binding deficient mutant of myc-GGA3 reduces the proportion of GLUT4 loaded into a subcellular fraction enriched in GSVs, suggesting that GLUT4 ubiquitination is one of the signals for GGA dependent sorting into GSVs. As ubiquitination is usually thought of as a signal to direct lysosomal degradation, and only 0.1 % of total GLUT4 is ubiquitinated at any one time, there may be a role for a deubiquitination step in ubiquitin dependent GLUT4 traffic. Work by our collaborator (Nai-Wen Chi, UCSD) has demonstrated that the GSV cargo IRAP and its binding partner tankyrase-1 are required for normal insulin responsive GLUT4 traffic. An interaction between tankyrase and the deubiquitinase (DUB) USP25 has been demonstrated by yeast two hybrid analysis, and this DUB contains a putative tankyrase binding motif. USP25 may therefore be recruited to GSVs by IRAP, with tankyrase acting as a scaffold. I demonstrated that GST-USP25 binds tankyrase-1 from an adipocyte lysate, and that a version of the enzyme with a mutation in the putative tankyrase binding motif (GST-USP25 R1049A) does not. I also used siRNA to deplete USP25 from 3T3-L1 adipocytes, and found that this results in a reduction of GLUT4 levels in these cells. A concomitant reduction in the fold change of insulin-stimulated glucose transport into these cells suggests that GLUT4 is not sequestered in GSVs, but is rather directed to the lysosome. In summary, my data show that ubiquitination of GLUT4 is required for the transporter to be loaded into its insulin responsive compartment (GSVs). I also began to characterise the role of the ubiquitin binding GAT domain of GGA3 and the deubiquitinase USP25 in GLUT4 traffic, opening up two further avenues for research into the insulin regulated trafficking of GLUT4

Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

Managed Control of Composite Cloud Systems

Cloud providers have just begun to provide primitive functionality enabling users to configure and easily provision resources, primarily in the infrastructure as a service domain. In order to effectively manage cloud resources in an automated fashion, systems must automate quality-of-service (QoS) metric measurement as a part of a larger usage management strategy. Collected metrics can then be used within control loops to manage and provision cloud resources. This basic approach can be scaled to monitor the use of system artifacts as well as simple QoS parameters, and can also address the needs of large systems spanning the boundaries of single service providers though the problem seems to moving toward intractability

Neurogenesis Deep Learning

Neural machine learning methods, such as deep neural networks (DNN), have achieved remarkable success in a number of complex data processing tasks. These methods have arguably had their strongest impact on tasks such as image and audio processing - data processing domains in which humans have long held clear advantages over conventional algorithms. In contrast to biological neural systems, which are capable of learning continuously, deep artificial networks have a limited ability for incorporating new information in an already trained network. As a result, methods for continuous learning are potentially highly impactful in enabling the application of deep networks to dynamic data sets. Here, inspired by the process of adult neurogenesis in the hippocampus, we explore the potential for adding new neurons to deep layers of artificial neural networks in order to facilitate their acquisition of novel information while preserving previously trained data representations. Our results on the MNIST handwritten digit dataset and the NIST SD 19 dataset, which includes lower and upper case letters and digits, demonstrate that neurogenesis is well suited for addressing the stability-plasticity dilemma that has long challenged adaptive machine learning algorithms.Comment: 8 pages, 8 figures, Accepted to 2017 International Joint Conference on Neural Networks (IJCNN 2017