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SLOWPOKE is a new system to accurately quantify the effects of hypothetical optimizations on end-to-end throughput for microservice applications, without relying on tracing or a priori knowledge of the call graph. Microservice operators can use SLOWPOKE to ask what-if performance analysis questions of the form "What throughput could my retail application sustain if I optimized the shopping cart service from 10K req/s to 20K req/s?". Given a target service and its hypothetical optimization, SLOWPOKE employs a perfor- mance model that determines how to selectively slow down non-target services to preserve the relative effect of the optimization. It then performs profiling experiments to predict the end-to-end throughput, as if the optimization had been implemented. Applied to four real-world microservice applications, SLOWPOKE accurately quantifies optimization effects with a root mean squared error of only 2.07%. It is also effective in more complex scenarios, e.g., predicting throughput after scaling optimizations or when bottlenecks arise from mutex contention. Evaluated in large-scale deployments of 45 nodes and 108 synthetic benchmarks, SLOWPOKE further demonstrates its scalability and coverage of a wide range of microservice characteristics. 

First release of NG-Scope with IEEE Spectrum Consumption Model (SCM) support. 

Yarrowia lipolyticaexcels in microbial lipid production, thriving across diverse conditions. Batch or fed-batch fermentation is the not only common practice to achieve higher lipid titer and yield but it is also subject to lower lipid productivity. Single-stage continuous fermentation (CF) provides a great potential for significantly higher productivity, but genetic instability is often seen and challenges strain performance over the long-period CF. This study harnesses single-stage CF to not only improve lipid productivity but also evolve high-lipid mutants from a previously engineeredY. lipolyticastrain E26 via adaptive laboratory evolution (ALE) in a continuous bioreactor, guided by a predictive kinetic model. The single-stage CF was run for 1128 hours (47 days) with key process parameters adjusted in a 1-L bioreactor to produce over 150 g/L yeast biomass, exceeding the targeted 113 g/L that is predicted by the model. Compared with the fed-batch fermentation process, the single-stage CF successfully improved lipid productivity from 0.3–0.5 g/L/h to about 1 g/L/h while maintaining the lipid yield at around 0.1 g/g. The CF sample at 1008 hours was used to isolate mutants with higher lipid production after ALE in the continuous bioreactor. A mutant E26E03 was identified, which demonstrated improvements in biomass, lipid content, and lipid yield by 43%, 30%, and 51%, respectively, over the original strain E26 in fed-batch fermentation. Our study indicated that using model-guided CF with ALE in a continuous bioreactor provides a great potential for significantly higher product titer, rate, and yield in biomanufacturing. 

Abstract A Low-rank Spectral Optimization Problem (LSOP) minimizes a linear objective function subject to multiple two-sided linear inequalities intersected with a low-rank and spectral constrained domain. Although solving LSOP is generally NP-hard, its partial convexification (i.e., replacing the domain with its convex hull), termed “LSOP-R, is often tractable and yields a high-quality solution. This motivates us to study the strength of LSOP-R. Specifically, we derive rank bounds for any extreme point of LSOP-R in different matrix spaces and prove their tightness. The proposed rank bounds recover two well-known results in the literature from a fresh angle and allow us to derive sufficient conditions under which the relaxation LSOP-R is equivalent to LSOP. To effectively solve LSOP-R, we develop a column generation algorithm with a vector-based convex pricing oracle and a rank-reduction algorithm, which ensures that the output solution always satisfies the theoretical rank bound. Finally, we numerically verify the strength of LSOP-R and the efficacy of the proposed algorithms. 

Abstract Distributionally Favorable Optimization (DFO) is a framework for decision-making under uncertainty, with applications spanning various fields, including reinforcement learning, online learning, robust statistics, chance-constrained programming, and two-stage stochastic optimization without complete recourse. In contrast to the traditional Distributionally Robust Optimization (DRO) paradigm, DFO presents a unique challenge– the application of the inner infimum operator often fails to retain the convexity. In light of this challenge, we study the tractability and complexity of DFO. We establish sufficient and necessary conditions for determining when DFO problems are tractable (i.e., solvable in polynomial time) or intractable (i.e., not solvable in polynomial time). Despite the typical nonconvex nature of DFO problems, our results show that they are mixed-integer convex programming representable (MICP-R), thereby enabling solutions via standard optimization solvers. Finally, we numerically validate the efficacy of our MICP-R formulations. 

Surrogate selection is an experimental design that without sequencing any DNA can restrict a sample of cells to those carrying certain genomic mutations. In immunological disease studies, this design may provide a relatively easy approach to enrich a lymphocyte sample with cells relevant to the disease response because the emergence of neutral mutations associates with the proliferation history of clonal subpopulations. A statistical analysis of clonotype sizes provides a structured, quantitative perspective on this useful property of surrogate selection. Our model specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires. 

We consider the infinite-horizon, average-reward restless bandit problem in discrete time. We propose a new class of policies that are designed to drive a progressively larger subset of arms toward the optimal distribution. We show that our policies are asymptotically optimal with an [Formula: see text] optimality gap for an N-armed problem, assuming only a unichain and aperiodicity assumption. Our approach departs from most existing work that focuses on index or priority policies, which rely on the Global Attractor Property to guarantee convergence to the optimum, or a recently developed simulation-based policy, which requires a Synchronization Assumption.