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Current strategies to target RNA splicing mutant myeloid cancers proposes targeting the remaining splicing apparatus. This approach has only been modestly sensitizing and is also toxic to non-mutant-bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of missplicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (acute myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia) was performed to identify conserved missplicing events. From this analysis, we identified that the cell-cycle and DNA repair pathways were overrepresented within the conserved misspliced transcript sets. In parallel, to functionally define pathways essential for survival and proliferation of Srsf2P95H/+ cells, we performed a genome-wide Clustered regularly interspaced short palindromic repeat loss-of-function screen using Hoxb8 immortalized R26-CreERki/+Srsf2P95H/+ and R26-CreERki/+Srsf2+/+ cell lines. We assessed loss of single guide RNA representation at 3 timepoints: immediately after Srsf2P95H/+ activation, and at 1 week and 2 weeks after Srsf2P95H/+ mutation. Pathway analysis demonstrated that the cell-cycle and DNA damage response pathways were among the top synthetic lethal pathways with Srsf2P95H/+ mutation. Based on the loss of guide RNAs targeting Cdk6, we identified that palbociclib, a CDK6 inhibitor, showed preferential sensitivity in Srsf2P95H/+ cell lines and in primary nonimmortalized lin-cKIT+Sca-1+ cells compared with wild-type controls. Our data strongly suggest that the cell-cycle and DNA damage response pathways are required for Srsf2P95H/+ cell survival, and that palbociclib could be an alternative therapeutic option for targeting SRSF2 mutant cancers.

Network science plays a big role in the representation of real-world phenomena such as user-item bipartite networks presented in e-commerce or social media platforms. It provides researchers with tools and techniques to solve complex real-world problems. Identifying and predicting future popularity and importance of items in e-commerce or social media platform is a challenging task. Some items gain popularity repeatedly over time while some become popular and novel only once. This work aims to identify the key-factors: popularity and novelty. To do so, we consider two types of novelty predictions: items appearing in the popular ranking list for the first time; and items which were not in the popular list in the past time window, but might have been popular before the recent past time window. In order to identify the popular items, a careful consideration of macro-level analysis is needed. In this work we propose a model, which exploits item level information over a span of time to rank the importance of the item. We considered ageing or decay effect along with the recent link-gain of the items. We test our proposed model on four various real-world datasets using four information retrieval based metrics.

Objectives. To understand the current risk of HIV infection and transmission and further elucidate the underlying risk factors among men who have sex with men and women (MSMW) in China. Methods. Following PRISMA guidelines, we conducted a systematic review and meta-analysis of searching through Chinese and English available literature databases between January 2000 and June 2014 to identify articles. Results. Thirty-six articles (including 19,730 MSMW and 53,536 MSMO) met the selection criteria and the aggregated results found that MSMW have significantly higher HIV prevalence than MSMO (6.6% versus 5.4%, OR = 1.27, 95% CI = 1.01-1.58). A higher proportion of MSMW had commercial male partners in the past 6 months (18.3% versus 12.2%, OR = 1.56, 95% CI = 1.01-2.42). Additionally, substance use in the past 6 months was significantly more frequent among MSMW than MSMO (alcohol use: 27.1% versus 13.1%, OR = 2.53, 95% CI = 2.14-2.99; illicit drug use: 5.3% versus 2.5%, OR = 2.09, 95% CI = 1.48-2.95). Conclusion. A higher proportion of commercial sex and substance use among MSMW may be a potentially indicative factor for significantly higher HIV prevalence compared to MSMO. Targeted interventions should aim at increasing the frequency of HIV/STIs screening and preventing high risk commercial sex and substance use among MSMW to decrease their HIV transmission to the general population.

Real-time grasping force optimization problem can be naturally formulated as a convex optimization problem on the Riemannian manifold of positive definite matrices subject to linear constraints for which many algorithms, including gradient algorithms, Newton algorithms, and interior point algorithms, have been developed. In all these algorithms we need to specify a step size in every iteration and a valid initial point to start the recursion. In this paper we propose several strategies for selecting such a step size according to the properties of each algorithm and one method for searching a valid initial point. Simulation and experimental results show the different performances of these algorithms from computation time and convergence rates.

Real-time grasping force optimization problem can be naturally formulated as a convex optimization problem on the Riemannian manifold of positive definite matrices subject to linear constraints for which many algorithms, including gradient algorithms, Newton algorithms, and interior point algorithms, have been developed. In all these algorithms we need to specify a step size in every iteration and a valid initial point to start the recursion. In this paper we propose several strategies for selecting such a step size according to the properties of each algorithm and one method for searching a valid initial point. Simulation and experimental results show the different performances of these algorithms from computation time and convergence rates.

Real-time grasping force optimization problem can be naturally formulated as a convex optimization problem on the Riemannian manifold of positive definite matrices subject to linear constraints for which many algorithms, including gradient algorithms, Newton algorithms, and interior point algorithms, have been developed. In all these algorithms we need to specify a step size in every iteration and a valid initial point to start the recursion. In this paper we propose several strategies for selecting such a step size according to the properties of each algorithm and one method for searching a valid initial point. Simulation and experimental results show the different performances of these algorithms from computation time and convergence rates.