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Evolutionary design is a widely accepted practice for defining microservice boundaries. It is performed through a sequence of incremental refactoring tasks (we call it “microservice refactoring”), each restructuring only part of a microservice system (a.k.a., refactoring part) into well-defined services for improving the architecture in a controlled manner. Despite its popularity in practice, microservice refactoring suffers from insufficient methodological support. While there are numerous studies addressing similar software design tasks, i.e., software remodularization and microservitization, their approaches prove inadequate when applied to microservice refactoring. Our analysis reveals that their approaches may even degrade the entire architecture in microservice refactoring, as they only optimize the refactoring part in such applications, but neglect the relationships between the refactoring part and the remaining system. As the first response to the need, Micro2Micro is proposed to re-partition the refactoring part while optimizing three quality objectives including the interdependence between the refactoring and non-refactoring parts. In addition, it allows architects to intervene in the decision-making process by interactively incorporating their knowledge into the iterative search for optimal refactoring solutions. An empirical study on 13 open-source projects of different sizes shows that the solutions from Micro2Micro perform well and exhibit quality improvement with an average up to 45% to the original architecture. Users of Micro2Micro found the suggested solutions highly satisfactory. They acknowledge the advantages in terms of infusing human intelligence into decisions, providing immediate quality feedback, and quick exploration capability. 

Abstract The ICESat‐2 and GEDI missions were launched in 2018, becoming the new generation of space‐borne laser altimeters. These missions provide unprecedented global geodetic elevations, opening great opportunities for water level monitoring. The potential of these altimeters has been demonstrated in open‐water environments such as lakes, rivers, and reservoirs. However, detailed evaluations in vegetated environments, such as wetlands, floodplains, and other areas not constrained by water canal networks, are essential for continued improvement and further hydrological application. We developed a systematic accuracy assessment of ICESat‐2 ATL08, and GEDI L2A products to monitor spatial‐temporal water level and depth dynamics over the South Florida Everglades wetlands. The evaluation was performed on data acquired between 2020 and 2021, using gauge‐based water level and depth estimates as references. The results showed an RMSE of 0.17 m (water level) and 0.15 m (water depth) for ICESat‐2 and 0.75 m (water level) and 0.37 m (water depth) for GEDI. The analysis suggested that nighttime acquisitions were more accurate for both missions than daytime ones. The low‐power beams achieved slightly higher accuracies than those of the high‐power beams over the evaluated wetlands. Water level retrieval was more problematic in densely vegetated areas; however, we derived a correction model based on the leaf area index that improved the accuracy by up to 75% for water depth retrievals from GEDI. Furthermore, the analysis provides new insights to understand the potential of the altimeters in monitoring the spatial‐temporal dynamics of water levels in the evaluated wetlands. 

Many techniques were proposed for detecting software misconfigurations in cloud systems and for diagnosing unintended behavior caused by such misconfigurations. Detection and diagnosis are steps in the right direction: misconfigurations cause many costly failures and severe performance issues. But, we argue that continued focus on detection and diagnosis is symptomatic of a more serious problem: configuration design and implementation are not yet first-class software engineering endeavors in cloud systems. Little is known about how and why developers evolve configuration design and implementation, and the challenges that they face in doing so. This paper presents a source-code level study of the evolution of configuration design and implementation in cloud systems. Our goal is to understand the rationale and developer practices for revising initial configuration design/implementation decisions, especially in response to consequences of misconfigurations. To this end, we studied 1178 configuration-related commits from a 2.5 year version-control history of four large-scale, actively-maintained open-source cloud systems (HDFS, HBase, Spark, and Cassandra). We derive new insights into the software configuration engineering process. Our results motivate new techniques for proactively reducing misconfigurations by improving the configuration design and implementation process in cloud systems. We highlight a number of future research directions. 

Abstract Wireframe DNA origami assemblies can now be programmed automatically from the top-down using simple wireframe target geometries, or meshes, in 2D and 3D, using either rigid, six-helix bundle (6HB) or more compliant, two-helix bundle (DX) edges. While these assemblies have numerous applications in nanoscale materials fabrication due to their nanoscale spatial addressability and high degree of customization, no easy-to-use graphical user interface software yet exists to deploy these algorithmic approaches within a single, standalone interface. Further, top-down sequence design of 3D DX-based objects previously enabled by DAEDALUS was limited to discrete edge lengths and uniform vertex angles, limiting the scope of objects that can be designed. Here, we introduce the open-source software package ATHENA with a graphical user interface that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami using DX or 6HB edges, including irregular, asymmetric DX-based polyhedra with variable edge lengths and vertices demonstrated experimentally, which significantly expands the set of possible 3D DNA-based assemblies that can be designed. ATHENA also enables external editing of sequences using caDNAno, demonstrated using asymmetric nanoscale positioning of gold nanoparticles, as well as providing atomic-level models for molecular dynamics, coarse-grained dynamics with oxDNA, and other computational chemistry simulation approaches. 

Prokaryotes and viruses have fought a long battle against each other. Prokaryotes use CRISPR–Cas-mediated adaptive immunity, while conversely, viruses evolve multiple anti-CRISPR (Acr) proteins to defeat these CRISPR–Cas systems. The type I-F CRISPR–Cas system in Pseudomonas aeruginosa requires the crRNA-guided surveillance complex (Csy complex) to recognize the invading DNA. Although some Acr proteins against the Csy complex have been reported, other relevant Acr proteins still need studies to understand their mechanisms. Here, we obtain three structures of previously unresolved Acr proteins (AcrF9, AcrF8, and AcrF6) bound to the Csy complex using electron cryo-microscopy (cryo-EM), with resolution at 2.57 Å, 3.42 Å, and 3.15 Å, respectively. The 2.57-Å structure reveals fine details for each molecular component within the Csy complex as well as the direct and water-mediated interactions between proteins and CRISPR RNA (crRNA). Our structures also show unambiguously how these Acr proteins bind differently to the Csy complex. AcrF9 binds to key DNA-binding sites on the Csy spiral backbone. AcrF6 binds at the junction between Cas7.6f and Cas8f, which is critical for DNA duplex splitting. AcrF8 binds to a distinct position on the Csy spiral backbone and forms interactions with crRNA, which has not been seen in other Acr proteins against the Csy complex. Our structure-guided mutagenesis and biochemistry experiments further support the anti-CRISPR mechanisms of these Acr proteins. Our findings support the convergent consequence of inhibiting degradation of invading DNA by these Acr proteins, albeit with different modes of interactions with the type I-F CRISPR–Cas system. 

Abstract Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Gα bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Gα at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Gα binding sites. The C-terminus of Gα is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Gα beta sheet and switch II to stabilize the nucleotide-free state of Gα. 

Human gastric pathogenHelicobacter pylori(H. pylori) is the primary risk factor for gastric cancer and is one of the most prevalent carcinogenic infectious agents. Vacuolating cytotoxin A (VacA) is a key virulence factor secreted byH. pyloriand induces multiple cellular responses. Although structural and functional studies of VacA have been extensively performed, the high-resolution structure of a full-length VacA protomer and the molecular basis of its oligomerization are still unknown. Here, we use cryoelectron microscopy to resolve 10 structures of VacA assemblies, including monolayer (hexamer and heptamer) and bilayer (dodecamer, tridecamer, and tetradecamer) oligomers. The models of the 88-kDa full-length VacA protomer derived from the near-atomic resolution maps are highly conserved among different oligomers and show a continuous right-handed β-helix made up of two domains with extensive domain–domain interactions. The specific interactions between adjacent protomers in the same layer stabilizing the oligomers are well resolved. For double-layer oligomers, we found short- and/or long-range hydrophobic interactions between protomers across the two layers. Our structures and other previous observations lead to a mechanistic model wherein VacA hexamer would correspond to the prepore-forming state, and the N-terminal region of VacA responsible for the membrane insertion would undergo a large conformational change to bring the hydrophobic transmembrane region to the center of the oligomer for the membrane channel formation.