Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay

The transcriptome in a cell is finely regulated by a large number of molecular mechanisms able to control the balance between mRNA production and degradation. Recent experimental findings have evidenced that fine and specific regulation of degradation is needed for proper orchestration of a global cell response to environmental conditions. We developed a computational technique based on stochastic modeling, to infer condition-specific individual mRNA half-lives directly from gene expression time-courses. Predictions from our method were validated by experimentally measured mRNA decay rates during the intraerythrocytic developmental cycle of Plasmodium falciparum. We then applied our methodology to publicly available data on the reproductive and metabolic cycle of budding yeast. Strikingly, our analysis revealed, in all cases, the presence of periodic changes in decay rates of sequentially induced genes and co-ordination strategies between transcription and degradation, thus suggesting a general principle for the proper coordination of transcription and degradation machinery in response to internal and/or external stimuli. Citation: Cacace F, Paci P, Cusimano V, Germani A, Farina L (2012) Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay. PLoS Comput Biol 8(11): e1002772. doi:10.1371/journal.pcbi.100277

Okapi: Causally Consistent Geo-Replication Made Faster, Cheaper and More Available

Okapi is a new causally consistent geo-replicated key- value store. Okapi leverages two key design choices to achieve high performance. First, it relies on hybrid logical/physical clocks to achieve low latency even in the presence of clock skew. Second, Okapi achieves higher resource efficiency and better availability, at the expense of a slight increase in update visibility latency. To this end, Okapi implements a new stabilization protocol that uses a combination of vector and scalar clocks and makes a remote update visible when its delivery has been acknowledged by every data center. We evaluate Okapi with different workloads on Amazon AWS, using three geographically distributed regions and 96 nodes. We compare Okapi with two recent approaches to causal consistency, Cure and GentleRain. We show that Okapi delivers up to two orders of magnitude better performance than GentleRain and that Okapi achieves up to 3.5x lower latency and a 60% reduction of the meta-data overhead with respect to Cure