Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Development and validation of kinase activity reporters for the dynamic study of cell response modalities by microscopy

Necroptosis is defined as a caspase-independent programmed cell death and relies on a signaling pathway involving two serine-threonine kinases: Receptor-Interacting Protein Kinase 1 and 3 (RIPK1 and RIPK3) and the pseudo-kinase Mixed-Lineage Kinase Like (MLKL). Activation of Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2) was reported to be involved in different modes of programmed cell death. It is now accepted that the regulation of the duration, magnitude and subcellular compartmentalization of ERK1/2 activity by specific spatio-temporal regulators is interpreted by the cell towards cell fate determination. ERK1/2 inhibition delays TNFα-induced necroptosis in L929 cells in a dose dependent manner but did not block it, providing arguments for a pro-necrotic function of ERK1/2. In this context, a compartmentalized biphasic phosphorylation of ERK1/2 was observed. Our results indicate a RIPK1-dependent phosphorylation of ERK1/2. Owing to the importance of ERK1/2 spatio-temporal dynamics in determining cellular responses, we developed a new reporter of ERK2 localization named ERK2-LOC. We observed a transient translocation of ERK2 when necroptosis was triggered in L929 upon TNFα stimulation, followed by progressive ERK2 accumulation in the nucleus. ERK1/2 activities were monitored during necroptosis using a FRET-based kinase biosensor for ERK1/2 (ERK1/2-ACT). Using ERK1/2-ACT, a dedicated spatio-temporal signature of ERK1/2 activity was recorded during necroptosis. Finally, to correlate ERK1/2 activity code with necroptosis occurrence, we also engineered a first generation of FRET biosensors to report on both RIPK1 and RIPK3 activities during necroptosis

Drug development progress in duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space