An elusive facet of high-impact research is translation to production. Production deployments are intrinsically complex and specialized, whereas research exploration requires stripping away incidental complexity and extraneous requirements to create clarity and generality. Conventional wisdom suggests that promising research rarely holds up once simplifying assumptions and missing features are addressed. This paper describes a productization methodology that led to a striking result: outperforming the mature and highly optimized state of the art by more than 10%. Concretely, this experience paper captures lessons from translating a high-performance research garbage collector published at PLDI’22, called LXR, to a hyperscale revenue-critical application. Key to our success was a new process that dovetails best practice research methodology with industrial processes, at each step assuring that neither research metrics nor production measures regressed. This paper makes three contributions, i) We advance the state of the art, nearly halving the cost of garbage collection, ii) We advance research translation by sharing our approach and five actionable lessons, iii) We pose questions about how the community should evaluate innovative ideas in mature and heavily productized fields. We deliver an optimized version of LXR. This collector, as far as we are aware, is the fastest general- purpose garbage collector for Java to date. On standard workloads, it substantially outperforms OpenJDK’s default G1 collector and the prior version of LXR, while also meeting Google internal correctness and uptime requirements. We address all of the limitations identified in the PLDI’22 paper. We use this experience to illustrate the following key lessons that are concrete, actionable, and transferable. LI) A systematic combination of research and production methodologies can meet production objectives while simultaneously advancing the research state-of-the-art. L2) A benchmark suite cannot and need not contain facsimiles of production workloads. It is sufficient to replicate individual pathologies that manifest in production (e.g., allocation rates, trace rates, heap constraints, etc.) or configure the JVM to force a workload to manifest the pathology. L3) Productization experiences can strengthen research workloads; we upstreamed one such workload. L4) Production environment requirements are myriad and sometimes prosaic, extending well beyond those that can reasonably be addressed in a research paper. L5) This collector is not yet in production, reminding us that replacing core technology in industry is a challenging sociotechnical problem. The artifact we deliver gives practitioners and researchers a new benchmark for high performance garbage collection. The lessons we enumerate should help academic and industrial researchers with actionable steps to close the gap between research paper results and industrial impact. The 10% ‘productization dividend’ the process delivered should spark discussion about how our field evaluates innovative ideas in mature areas.

Protein phosphorylation is a reversible and ubiquitous post-translational modification that primarily occurs at serine, threonine and tyrosine residues and regulates a variety of biological processes. In this paper, we first briefly summarized the current progresses in computational prediction of eukaryotic protein phosphorylation sites, which mainly focused on animals and plants, especially on human, with a less extent on fungi. Since the number of identified fungi phosphorylation sites has greatly increased in a wide variety of organisms and their roles in pathological physiology still remain largely unknown, more attention has been paid on the identification of fungi-specific phosphorylation. Here, experimental fungi phosphorylation sites data were collected and most of the sites were classified into different types to be encoded with various features and trained via a two-step feature optimization method. A novel method for prediction of species-specific fungi phosphorylation-PreSSFP was developed, which can identify fungi phosphorylation in seven species for specific serine, threonine and tyrosine residues (http://computbiol.ncu.edu.cn/PreSSFP). Meanwhile, we critically evaluated the performance of PreSSFP and compared it with other existing tools. The satisfying results showed that PreSSFP is a robust predictor. Feature analyses exhibited that there have some significant differences among seven species. The species-specific prediction via two-step feature optimization method to mine important features for training could considerably improve the prediction performance. We anticipate that our study provides a new lead for future computational analysis of fungi phosphorylation.

Accumulative studies have indicated that amino acid variations through changing the type of residues of the target sites or key flanking residues could directly or indirectly influence protein posttranslational modifications (PTMs) and bring about a detrimental effect on protein function. Computational mutation analysis can greatly narrow down the efforts on experimental work. To increase the utilization of current computational resources, we first provide an overview of computational prediction of amino acid variations that influence protein PTMs and their functional analysis. We also discuss the challenges that are faced while developing novel in silico approaches in the future. The development of better methods for mutation analysis-related protein PTMs will help to facilitate the development of personalized precision medicine.

MOTIVATION: Protein glycation is a familiar post-translational modification (PTM) which is a two-step non-enzymatic reaction. Glycation not only impairs the function but also changes the characteristics of the proteins so that it is related to many human diseases. It is still much more difficult to systematically detect glycation sites due to the glycated residues without crucial patterns. Computational approaches, which can filter supposed sites prior to experimental verification, can extremely increase the efficiency of experiment work. However, the previous lysine glycation prediction method uses a small number of training datasets. Hence, the model is not generalized or pervasive. RESULTS: By searching from a new database, we collected a large dataset in Homo sapiens. PredGly, a novel software, can predict lysine glycation sites for H.sapiens, which was developed by combining multiple features. In addition, XGboost was adopted to optimize feature vectors and to improve the model performance. Through comparing various classifiers, support vector machine achieved an optimal performance. On the basis of a new independent test set, PredGly outperformed other glycation tools. It suggests that PredGly can provide more instructive guidance for further experimental research of lysine glycation. AVAILABILITY AND IMPLEMENTATION: https://github.com/yujialinncu/PredGly. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Lysine acetylation exists extensively in prokaryotes, and plays a vital role in function adjustment. Recent progresses in the identification of prokaryote acetylation substrates and sites provide a great opportunity to explore the difference of substrate site specificity between prokaryotic and eukaryotic acetylation. Motif analysis suggests that prokaryotic and eukaryotic acetylation sites have distinct location-specific difference, and it is necessary to develop a prokaryote-specific acetylation sites prediction tool. Results: Therefore, we collected nine species of prokaryote lysine acetylation data from various databases and literature, and developed a novel online tool named ProAcePred for predicting prokaryote lysine acetylation sites. Optimization of feature vectors via elastic net could considerably improve the prediction performance. Feature analyses demonstrated that evolutionary information played significant roles in prediction model for prokaryote acetylation. Comparison between our method and other tools suggested that our species-specific prediction outperformed other existing works. We expect that the ProAcePred could provide more instructive help for further experimental investigation of prokaryotes acetylation. Availability and implementation: http://computbiol.ncu.edu.cn/ProAcePred. Supplementary information: Supplementary data are available at Bioinformatics online.

This paper presents Fast Instrumentation Bias (FIB), a sound and complete dynamic data race detection algorithm that improves performance by reducing or eliminating the costs of analysis atomicity. In addition to checking for errors in target programs, dynamic data race detectors must introduce synchronization to guard against metadata races that may corrupt analysis state and compromise soundness or completeness. Pessimistic analysis synchronization can account for nontrivial performance overhead in a data race detector. The core contribution of FIB is a novel cooperative ownership-based synchronization protocol whose states and transitions are derived purely from preexisting analysis metadata and logic in a standard data race detection algorithm. By exploiting work already done by the analysis, FIB ensures atomicity of dynamic analysis actions with zero additional time or space cost in the common case. Analysis of temporally thread-local or read-shared accesses completes safely with no synchronization. Uncommon write-sharing transitions require synchronous cross-thread coordination to ensure common cases may proceed synchronization-free. We implemented FIB in the Jikes RVM Java virtual machine. Experimental evaluation shows that FIB eliminates nearly all instrumentation atomicity costs on programs where data often experience windows of thread-local access. Adaptive extensions to the ownership policy effectively eliminate high coordination costs of the core ownership protocol on programs with high rates of serialized sharing. FIB outperforms a naive pessimistic synchronization scheme by 50% on average. Compared to a tuned optimistic metadata synchronization scheme based on conventional fine-grained atomic compare-and-swap operations, FIB is competitive overall, and up to 17% faster on some programs. Overall, FIB effectively exploits latent analysis and program invariants to bring strong integrity guarantees to an otherwise unsynchronized data race detection algorithm at minimal cost.

Shared-memory parallel programs are hard to get right. A major challenge is that language and hardware memory models allow unexpected, erroneous behaviors for executions containing data races. Researchers have introduced dynamic analyses that expose weak memory model behaviors, but these approaches cannot expose behaviors due to loading a "future value" -- a value written by a program store that executes after the program load that uses the value. This paper presents prescient memory (PM), a novel dynamic analysis that exposes behaviors due to future values. PM speculatively returns a future value at a program load, and tries to validate the speculative value at a later store. To enable PM to expose behaviors due to future values in real application executions, we introduce a novel approach that increases the chances of using and successfully validating future values, by profiling and predicting future values and guiding execution. Experiments show that our approach is able to uncover a few previously unknown behaviors due to future values in benchmarked versions of real applications. Overall, PM overcomes a key limitation of existing approaches, broadening the scope of program behaviors that dynamic analyses can expose.

It is notoriously challenging to develop parallel software systems that are both scalable and correct. Runtime support for parallelism---such as multithreaded record & replay, data race detectors, transactional memory, and enforcement of stronger memory models---helps achieve these goals, but existing commodity solutions slow programs substantially in order to track (i.e., detect or control) an execution's cross-thread dependences accurately. Prior work tracks cross-thread dependences either "pessimistically," slowing every program access, or "optimistically," allowing for lightweight instrumentation of most accesses but dramatically slowing accesses involved in cross-thread dependences.

Software transactional memory offers an appealing alternative to locks by improving programmability, reliability, and scalability. However, existing STMs are impractical because they add high instrumentation costs and often provide weak progress guarantees and/or semantics. This paper introduces a novel STM called LarkTM that provides three significant features. (1) Its instrumentation adds low overhead except when accesses actually conflict, enabling low single-thread overhead and scaling well on low-contention workloads. (2) It uses eager concurrency control mechanisms, yet naturally supports flexible conflict resolution, enabling strong progress guarantees. (3) It naturally provides strong atomicity semantics at low cost. LarkTM's design works well for low-contention workloads, but adds significant overhead under higher contention, so we design an adaptive version of LarkTM that uses alternative concurrency control for high-contention objects. An implementation and evaluation in a Java virtual machine show that the basic and adaptive versions of LarkTM not only provide low single-thread overhead, but their multithreaded performance compares favorably with existing high-performance STMs.

Parallel programming is essential for reaping the benefits of parallel hardware, but it is notoriously difficult to develop and debug reliable, scalable software systems. One key challenge is that modern languages and systems provide poor support for ensuring concurrency correctness properties - atomicity, sequential consistency, and multithreaded determinism - because all existing approaches are impractical. Dynamic, software-based approaches slow programs by up to an order of magnitude because capturing and controlling cross-thread dependences (i.e., conflicting accesses to shared memory) requires synchronization at virtually every access to potentially shared memory.