Snapshot Provisioning of Cloud Application Stacks to Face Traffic Surges

Traffic surges, like the Slashdot effect, occur when a web application is overloaded by a huge number of requests, potentially leading to unavailability. Unfortunately, such traffic variations are generally totally unplanned, of great amplitude, within a very short period, and a variable delay to return to a normal regime. In this report, we introduce PeakForecast as an elastic middleware solution to detect and absorb a traffic surge. In particular, PeakForecast can, from a trace of queries received in the last seconds, minutes or hours, to detect if the underlying system is facing a traffic surge or not, and then estimate the future traffic using a forecast model with an acceptable precision, thereby calculating the number of resources required to absorb the remaining traffic to come. We validate our solution by experimental results demonstrating that it can provide instantaneous elasticity of resources for traffic surges observed on the Japanese version of Wikipedia during the Fukushima Daiichi nuclear disaster in March 2011.Les pics de trafic, tels que l'effet Slashdot, apparaissent lorsqu'une application web doit faire face un nombre important de requêtes qui peut potentiellement entraîner une mise hors service de l'application. Malheureusement, de telles variations de traffic sont en général totalement imprévues et d'une grande amplitude, arrivent pendant une très courte période de temps et le retour à un régime normal prend un délai variable. Dans ce rapport, nous présentons PeakForecast qui est une solution intergicielle élastique pour détecter et absorber les pics de trafic. En particulier, PeakForecast peut, à partir des traces de requêtes reçues dans les dernières secondes, minutes ou heures, détecter si le système sous-jacent fait face ou non à un pic de trafic, estimer le trafic futur en utilisant un modèle de prédiction suffisamment précis, et calculer le nombre de ressources nécessaires à l'absorption du trafic restant à venir. Nous validons notre solution avec des résultats expérimentaux qui démontrent qu'elle fournit une élasticité instantanée des ressources pour des pics de trafic qui ont été observés sur la version japonaise de Wikipedia lors de l'accident nucléaire de Fukushima Daiichi en mars 2011

Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions

<p>Abstract</p> <p>Background</p> <p>The combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. In a malaria model system, it has been shown that the progression of <it>Plasmodium berghei </it>through <it>Anopheles stephensi </it>and the survival of the mosquito both depend non-linearly on parasite density. These processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (TBIs) currently under development.</p> <p>Methods</p> <p>An individual-based stochastic mathematical model is used to investigate the combined impact of these multiple regulatory processes and examine how TBIs, which target different parasite life-stages within the mosquito, may influence overall parasite transmission.</p> <p>Results</p> <p>The best parasite molecular targets will vary between different epidemiological settings. Interventions that reduce ookinete density beneath a threshold level are likely to have auxiliary benefits, as transmission would be further reduced by density-dependent processes that restrict sporogonic development at low parasite densities. TBIs which reduce parasite density but fail to clear the parasite could cause a modest increase in transmission by increasing the number of infectious bites made by a mosquito during its lifetime whilst failing to sufficiently reduce its infectivity. Interventions with a higher variance in efficacy will therefore tend to cause a greater reduction in overall transmission than a TBI with a more uniform effectiveness. Care should be taken when interpreting these results as parasite intensity values in natural parasite-vector combinations of human malaria are likely to be significantly lower than those in this model system.</p> <p>Conclusions</p> <p>A greater understanding of the development of the malaria parasite within the mosquito is required to fully evaluate the impact of TBIs. If parasite-induced vector mortality influenced the population dynamics of <it>Plasmodium </it>species infecting humans in malaria endemic regions, it would be important to quantify the variability and duration of TBI efficacy to ensure that community benefits of control measures are not overestimated.</p

Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation

Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis

A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells

Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50–100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry

Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

Background: Horizontal gene transfer (HGT) is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results: In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR) survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR) were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT)- PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions: This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native mitochondrial copies suggests that transferred genes may be evolutionarily important in generating mitochondrial genetic diversity. Finally, the complex relationships within each lineage of transferred genes imply a surprisingly complicated history of these genes in Plantago subsequent to their acquisition via HGT and this history probably involves some combination of additional transfers (including intracellular transfer), gene duplication, differential loss and mutation-rate variation. Unravelling this history will probably require sequencing multiple mitochondrial and nuclear genomes from Plantago

Australia's National Bowel Cancer Screening Program: does it work for Indigenous Australians?

<p>Abstract</p> <p>Background</p> <p>Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP) using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population.</p> <p>This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups.</p> <p>Methods</p> <p>A search was undertaken of peer-reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions.</p> <p>Results</p> <p>The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening.</p> <p>Conclusions</p> <p>Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating the already widening disparities in cancer outcomes that exist among Indigenous Australians. Modifications to the program are recommended to facilitate access and participation by Indigenous and other minority populations. Further research is also needed to understand the needs and social and cultural sensitivities of these groups around cancer screening and inform alternative approaches to bowel cancer screening.</p