Soroban: Attributing latency in virtualized environments

Applications running in the cloud have highly-variable response times due to the lack of perfect performance isolation from other services served by common infrastructure. In particular, response latency when executing on a loaded hypervisor or in a container is substantially higher than uncontested bare-metal performance. Whilst efforts to increase performance isolation continue, we present Soroban, a framework for attributing latency to either the cloud provider or their customer. Soroban allows cloud providers to instrument commonly used programs, such as a web server to determine, for each request, how much of the latency is due to the cloud provider, or the consumer. We apply Soroban to a HTTP server and show that it identifies when the cause of latency is due to a provider-induced activity, such as underprovisioning a host, or due to the software run by the customer.This is the author accepted manuscript. The final version is available from USENIX. via https://www.usenix.org/conference/hotcloud15/workshop-program/presentation/sne

Telomere elongation through hTERT immortalization leads to chromosome repositioning in control cells and genomic instability in Hutchinson-Gilford progeria syndrome fibroblasts, expressing a novel SUN1 isoform

© 2018 The Authors. Immortalising primary cells with hTERT has been common practice to enable primary cells to be of extended use in the laboratory since they avoid replicative senescence. Studying exogenously expressed hTERT in cells also affords scientists models of early carcinogenesis and telomere behaviour. Control and the premature ageing disease - Hutchinson-Gilford Progeria Syndrome primary dermal fibroblasts, with and without the classical G608G mutation have been immortalised with exogenous hTERT. However, hTERT immortalisation surprisingly elicits genome reorganisation, in disease cells but also in the normal control cells, such that whole chromosome territories normally located at the nuclear periphery in proliferating fibroblasts become mis-localised in the nuclear interior. This includes chromosome 18 in the control fibroblasts and both chromosomes 18 and X in HGPS cells, which physically express an isoform of the LINC complex protein SUN1 that has previously only been theoretical. Additionally, this HGPS cell line has also become genomically unstable and has a tetraploid karyotype, which could be due to the novel SUN1 isoform. Long term treatment with the hTERT inhibitor BIBR1532 enabled the reduction of telomere length in the immortalised cells and resulted in these mis-localised internal chromosomes to be located at the nuclear periphery, as assessed in actively proliferating cells. Taken together, these findings reveal that elongated telomeres lead to dramatic chromosome mis-localisation, which can be restored with a drug treatment that results in telomere re-shortening and that a novel SUN1 isoform combined with elongated telomeres leads to genomic instability. Thus, care should be taken when interpreting data from genomic studies in hTERT immortalised cell lines.Brunel Progeria Research Fun

Contribution of Caspase(s) to the Cell Cycle Regulation at Mitotic Phase

Caspases have been suggested to contribute to not only apoptosis regulation but also non-apoptotic cellular phenomena. Recently, we have reported the involvement of caspase-7 to the cell cycle progression at mitotic phase by knockdown of caspase-7 using small interfering RNAs and short hairpin RNA. Here we showed that chemically synthesized broad-spectrum caspase inhibitors, which have been used to suppress apoptosis, prevented the cell proliferation in a dose-dependent manner, and that the subtype-specific peptide-based caspase inhibitor for caspase-3 and -7, but not for caspase-9, inhibited cell proliferation. It was also indicated that the BIR2 domain of X-linked inhibitor of apoptosis protein, functioning as an inhibitor for caspase-3 and -7, but not the BIR3 domain which plays as a caspase-9 inhibitor, induced cell cycle arrest. Furthermore, flow cytometry revealed that the cells treated with caspase inhibitors arrested at G2/M phase. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, the prevention of the cell proliferation by caspase inhibitors induced cell cycle arrest at mitotic phase accompanying the accumulation of the substrates for APC/C, suggesting the impairment of the APC/C activity at the transition from M to G1 phases. These results indicate that caspase(s) contribute to the cell cycle regulation at mitotic phase

Preterm infants have significantly longer telomeres than their term born counterparts

There are well-established morbidities associated with preterm birth including respiratory, neurocognitive and developmental disorders. However several others have recently emerged that characterise an `aged' phenotype in the preterm infant by term-equivalent age. These include hypertension, insulin resistance and altered body fat distribution. Evidence shows that these morbidities persist into adult life, posing a significant public health concern. In this study, we measured relative telomere length in leukocytes as an indicator of biological ageing in 25 preterm infants at term equivalent age. Comparing our measurements with those from 22 preterm infants sampled at birth and from 31 term-born infants, we tested the hypothesis that by term equivalent age, preterm infants have significantly shorter telomeres (thus suggesting that they are prematurely aged). Our results demonstrate that relative telomere length is highly variable in newborn infants and is significantly negatively correlated with gestational age and birth weight in preterm infants. Further, longitudinal assessment in preterm infants who had telomere length measurements available at both birth and term age (n = 5) suggests that telomere attrition rate is negatively correlated with increasing gestational age. Contrary to our initial hypothesis however, relative telomere length was significantly shortest in the term born control group compared to both preterm groups and longest in the preterm at birth group. In addition, telomere lengths were not significantly different between preterm infants sampled at birth and those sampled at term equivalent age. These results indicate that other, as yet undetermined, factors may influence telomere length in the preterm born infant and raise the intriguing hypothesis that as preterm gestation declines, telomere attrition rate increases

The development, design, testing, refinement, simulation and application of an evaluation framework for communities of practice and social-professional networks

Background. Communities of practice and social-professional networks are generally considered to enhance workplace experience and enable organizational success. However, despite the remarkable growth in interest in the role of collaborating structures in a range of industries, there is a paucity of empirical research to support this view. Nor is there a convincing model for their systematic evaluation, despite the significant potential benefits in answering the core question: how well do groups of professionals work together and how could they be organised to work together more effectively? This research project will produce a rigorous evaluation methodology and deliver supporting tools for the benefit of researchers, policymakers, practitioners and consumers within the health system and other sectors. Given the prevalence and importance of communities of practice and social networks, and the extent of investments in them, this project represents a scientific innovation of national and international significance. Methods and design. Working in four conceptual phases the project will employ a combination of qualitative and quantitative methods to develop, design, field-test, refine and finalise an evaluation framework. Once available the framework will be used to evaluate simulated, and then later existing, health care communities of practice and social-professional networks to assess their effectiveness in achieving desired outcomes. Peak stakeholder groups have agreed to involve a wide range of members and participant organisations, and will facilitate access to various policy, managerial and clinical networks. Discussion. Given its scope and size, the project represents a valuable opportunity to achieve breakthroughs at two levels; firstly, by introducing novel and innovative aims and methods into the social research process and, secondly, through the resulting evaluation framework and tools. We anticipate valuable outcomes in the improved understanding of organisational performance and delivery of care. The project's wider appeal lies in transferring this understanding to other health jurisdictions and to other industries and sectors, both nationally and internationally. This means not merely publishing the results, but contextually interpreting them, and translating them to advance the knowledge base and enable widespread institutional and organisational application

Signals of opportunity geolocation methods for urban and indoor environments

Motivated by the geolocation requirements of future mobile network applications such as portable internet of things (IoT) devices and automated airborne drone systems, this paper aims to provide techniques for improving device geolocation estimates in urban and indoor locations. In these applications low size, weight and power are vital design constraints. This paper proposes methods for improving the geolocation estimate available to a system in indoor and urban environments without the need for addition sensing or transmitting hardware. This paper proposes novel system application techniques that enable the integration of signals of opportunity, providing a robust geolocation estimate without any additional hardware. The proposed method utilises a sinusoidal Kalman filter architecture to analyse raw radio frequency (RF) signals that surround a system in urban and indoor environments. The introduced techniques efficiently analyse the raw RF data from any signal of opportunity and combine it with higher level geolocation sensors to provide an improved geolocation estimate. The improvements achieved by the system in a range of environments have been simulated, analysed and compared to the results obtained using the prior art. These improvements have been further validated and benchmarked by hardware test. The results obtained provide evidence that the efficient use of signals of opportunity coupled with common navigation sensors can provide a robust and reliable geolocation system in indoor and urban environments