Towards Automatic Performance Tuning

When the computing environment becomes heterogeneous and applications become modular with reusable components, automatic performance tuning is needed for these applications to run well in different environments. We present the Active Harmony automated runtime tuning system and describe the interface used by programs to make applications tunable. We present the optimization algorithm used to adjust application parameters and the Library Specification Layer which helps program library developers expose multiple variations of the same API using different algorithms. By comparing the experience stored in a database, the tuning server is able to find appropriate configurations more rapidly. Utilizing historical data together with a mechanism that estimates performance speeds up the tuning process. To avoid performance oscillations during the initial phase of the tuning process, we use improved search refinement techniques that use configurations equally spaced throughout the performance search space to make the tuning process smoother. We also introduce a parameter prioritizing tool to focus on those performance critical parameters. We demonstrate how to reduce the time when tuning a large system with many tunable parameters. The search space can be reduced by checking the relations among parameters to avoid unnecessary search. In addition, for homogeneous processing nodes, we demonstrate how to use one set of the parameters and replicate the values to the remaining processing nodes. For environments where parameters can be divided into independent groups, an individual tuning server is used for each group. An algorithm is given to automatically adjust the structure of cluster-based web systems and it improves the system throughput up to 70%. We successfully apply the Active Harmony system to a cluster-based web service system and scientific programs. By tuning the parameters, Active Harmony helps the system adapt to different workloads and improve the performance up to 16%. The performance improvement cannot easily be achieved by tuning individual components for such a system and there is no single configuration that performs well for all kinds of workloads. All the design and experimental results show that Active Harmony is a feasible and useful tool in performance tuning

Automated Cluster-Based Web Service Performance Tuning

In this paper, we apply the Active Harmony system to improve the performance of a cluster-based web service system. The performance improvement cannot easily be achieved by tuning individual components for such a system. The experimental results show that there is no single configuration for the system that performs well for all kinds of workloads. By tuning the parameters, the Active Harmony helps the system adapt to different workloads and improve the performance up to 16%. For scalability, we demonstrate how to reduce the time when tuning a large system with many tunable parameters. Finally an algorithm is proposed to automatically adjust the structure of cluster-based web systems, and the system throughput is improved up to 70% using this technology. (UMIACS-TR-2003-84

Design of Scalable Continuous Media Servers with Dynamic Replication

Multimedia applications place high demands for quality-of-service (QoS), performance, and reliability on systems. These stringent requirements make design of cost-effective and scalable systems difficult. Therefore efficient adaptive and dynamic resource management techniques in conjunction with data placement techniques can be of great help in improving performance, scalability and reliability of such systems. In this paper, we first focus on data placement. In the recent past, a great deal of work has focused on "wide" data striping as a way of dealing with load imbalance problems caused by skews in data access patterns. Another approach to dealing with load imbalance problems is replication. The appropriate compromise between the degree of striping and the degree of replication is key to the design of scalable continuous media (CM) servers. In this work we focus on evaluation of this compromise in the context of a hybrid CM server design. Changes in data access patterns lead to other questions: (1) when should the system alter the number of copies of a CM object, and (2) how to accomplish this change. We address (1) through an adaptive threshold-based approach, and we use dynamic replication policies in conjunction with a mathematical model of user behavior to address (2). We do this without any knowledge of data access patterns and with provisions for full use of VCR functionality. Through a performance study, we show that not only does the use of this mathematical model in conjunction with dynamic resource management policies improves the system's performance but that it also facilitates reduced sensitivity to changes in:(a) workload characteristics, (b) skewness of data access patterns, and (c) frequency of changes in data access patterns. We believe that not only is this a desirable property for a CM server, in general, but that furthermore, it suggests the usefulness of these techniques across a wide range of continuous media applications. (Cross-referenced as UMIACS-TR-2001-21

Isocost Lines Describe the Cellular Economy of Genetic Circuits

Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings.United States. Air Force Office of Scientific Research (Grant FA9550-14-1-0060)United States. Defense Advanced Research Projects Agency (Contract W911NF-12-1-0540)National Institutes of Health (U.S.) (Grant P50 GM098792

Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.

Activation of the NLRP3 inflammasome is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Pyk2 is essential for NLRP3 inflammasome activation. Here we show that the Src-family kinases (SFKs)-Cbl axis plays a pivotal role in suppressing NLRP3 inflammasome activation in response to stimulation by nigericin or ATP, as assessed using gene knockout and gene knockdown cells, dominant active/negative mutants, and pharmacological inhibition. We reveal that the phosphorylation of Cbl is regulated by SFKs, and that phosphorylation of Cbl at Tyr371 suppresses NLRP3 inflammasome activation. Mechanistically, Cbl decreases the level of phosphorylated Pyk2 (p-Pyk2) through ubiquitination-mediated proteasomal degradation and reduces mitochondrial ROS (mtROS) production by contributing to the maintenance of mitochondrial size. The lower levels of p-Pyk2 and mtROS dampen NLRP3 inflammasome activation. In vivo, inhibition of Cbl with an analgesic drug, hydrocotarnine, increases inflammasome-mediated IL-18 secretion in the colon, and protects mice from dextran sulphate sodium-induced colitis. Together, our novel findings provide new insights into the role of the SFK-Cbl axis in suppressing NLRP3 inflammasome activation and identify a novel clinical utility of hydrocortanine for disease treatment