Here we present a modular, chemo‐, regio‐, and stereoselective synthesis of fully‐substituted and configuration‐defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive ...approach involves the chemo‐ and regioselective functionalization of the CF2 unit in gem‐difluorinated cyclopropanes with O−H and C−H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring‐opening process to produce fully‐substituted and configuration‐defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual‐functional copper catalysis, which is involved in both the functionalization of the CF2 unit and the subsequent ring‐opening process.
The synthesis of highly‐substituted alkyl vinyl ethers in a well‐defined configuration is challenging. Now, a modular, chemo‐, regio‐, and stereoselective synthesis of fully‐substituted and configuration‐defined alkyl vinyl ethers (AVEs) enabled by dual‐functional Cu catalysis is reported. It also represents a novel ring‐opening pattern involving the cleavage of the C1−C3 bond in gem‐difluorinated cyclopropanes.
Herein, we report an effective method to offer chiral gem-difluorinated cyclopropanes containing an all-carbon quaternary stereocenter by rhodium-catalyzed stereoablative kinetic resolution. The ...activation of a sterically hindered all-carbon quaternary C–C bond through oxidative addition with a chiral rhodium complex is proposed as the enantiodetermining step. A wide range of gem-difluorinated cyclopropanes can be obtained with excellent ee values (ee = 87% to >99.9%), which are demonstrated to be useful chiral fluorine-containing building blocks by a series of postfunctionalizations.
Here we present a modular, chemo‐, regio‐, and stereoselective synthesis of fully‐substituted and configuration‐defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive ...approach involves the chemo‐ and regioselective functionalization of the CF2 unit in gem‐difluorinated cyclopropanes with O−H and C−H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring‐opening process to produce fully‐substituted and configuration‐defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual‐functional copper catalysis, which is involved in both the functionalization of the CF2 unit and the subsequent ring‐opening process.
The synthesis of highly‐substituted alkyl vinyl ethers in a well‐defined configuration is challenging. Now, a modular, chemo‐, regio‐, and stereoselective synthesis of fully‐substituted and configuration‐defined alkyl vinyl ethers (AVEs) enabled by dual‐functional Cu catalysis is reported. It also represents a novel ring‐opening pattern involving the cleavage of the C1−C3 bond in gem‐difluorinated cyclopropanes.
•Semantic information should be considered to improve code search result quality.•An enhanced semantics-based code search using I/O examples•Code for search can have invocation to library APIs and ...more data types.•A customized keyword-based search to prune methods to be checked against IO examples.
As the quality and quantity of open source code increase, effective and efficient search for code implementing certain semantics, or semantics-based code search, has become an emerging need for software developers to retrieve and reuse existing source code. Previous techniques in semantics-based code search encode the semantics of loop-free Java code snippets as constraints and utilize an SMT solver to find encoded snippets that match an input/output (IO) query. We present in this article the Quebio approach to semantics-based search for Java methods. Quebio advances the state-of-the-art by supporting important language features like invocation to library APIs and enabling the search to handle more data types like array/List, Set, and Map. Compared with existing approaches, Quebio also integrates a customized keyword-based search that uses as the input a textual, behavioral summary of the desired methods to quickly prune the methods to be checked against the IO examples. To evaluate the effectiveness and efficiency of Quebio, we constructed a repository of 14,792 methods from 723 open source Java projects hosted on GitHub and applied the approach to resolve 47 queries extracted from StackOverflow. Quebio was able to find methods correctly implementing the specified IO behaviors for 43 of the queries, significantly outperforming the existing semantics-based code search techniques. The average search time with Quebio was 213.2 seconds for each query.
Although software libraries promote code reuse and facilitate software development, they increase the complexity of programme analysis tasks. To effectively analyse programmes built on top of ...software libraries, it is essential to have specifications for the library methods that can be easily processed by analysis tools. However, the availability of such specifications is seriously limited at the moment. Manually writing the specifications can be prohibitively expensive and error-prone, while existing automated approaches to inferring the specifications seldom produce results that are strong enough to be used in programme analysis. In this work, we propose the DOC2SMT approach to generating strong functional constraints in SMT for library methods based on their documentations. DOC2SMT first applies natural language processing (NLP) techniques and a set of rules to translate a method's natural language documentation into a large number of candidate constraint clauses in OCL. Then, it utilises a manually enhanced domain model to identify OCL candidate constraint clauses that comply with the problem domain in static validation, translates well-formed OCL constraints into the SMT-LIB format, and checks whether each 5MB-LIB constraint rightly abstracts the functionalities of the method under consideration via testing in dynamic validation. In the end, it reports the first functional constraint that survives both validations to the user as the result. We have implemented the approach into a supporting tool with the same name. In experiments conducted on 451 methods from the Java Collections Framework and the Java IO library, DOC2SMT generated correct constraints for 309 methods, with the average generation time for each correct constraint being merely 2.7 min. We have also applied the generated constraints to facilitate symbolic-execution-based test generation with the Symbolic Java PathFinder (SPF) tool. For 24 utility methods manipulating Java container and IO objects, SPF with access to the generated constraints produced 51.2 times more test cases than SPF without the access.
As the quality and quantity of open source code increase, semantics-based code search has become an emerging need for software developers to retrieve and reuse existing source code. We present an ...approach of semantics-based code search using input/output examples for the Java language. Our approach encodes Java methods in code repositories into path constraints via symbolic analysis and leverages SMT solvers to find the methods whose path constraints can satisfy the given input/output examples. Our approach extends the applicability of the semantics-based search technology to more general Java code compared with existing methods. To evaluate our approach, we encoded 1228 methods from GitHub and applied semantics-based code search on 35 queries extracted from Stack Overflow. Correct method code for 29 queries was obtained during the search and the average search time was just about 48 seconds.
Abstract This study investigates the diurnal cycles of convective activities and low-level winds with emphasis on their interactions during the East Asian summer monsoon. We categorize atmospheric ...convection states using satellite-derived cloud regimes and group southerly monsoon flows with different characteristics of diurnal cycles, and found that they are closely related to each other. Over South China, deep convection and associated cirrus anvils produce a strongly negative shortwave cloud radiative effect and induce anomalous cooling in the ABL in the daytime, which reduces the diurnal amplitude of monsoon flows during the night that follows. Conversely, a fair-weather state in the daytime leads to an anomalously warm ABL that enhances the subsequent nighttime acceleration of the monsoon southerlies. The dominant cloud regimes in the daytime over South China are closely related to whether the organized deep convection over the Yun-Gui Plateau (southeast of the Tibetan Plateau) propagates eastward during the preceding night. Such a precursor of clouds/convection governing wind diurnal amplitude indicates a possible predictability of monsoon diurnal cycles over South China. Further analyses show that the cloud regimes and induced monsoon diurnal cycles over South China can regulate the moist convection over the downstream region (central China) through modulating moisture transport and convergence. Therefore, the observational statistics of this study reveal a strong coupling of clouds, radiation, winds, and precipitation at the diurnal time scale over the summer monsoon regions, in which the cloud radiative effects of atmospheric convection can strongly regulate the diurnal variations of low-level winds that further influence precipitation downstream.
Mining-induced tremors serve as the main dynamic stress source of coal bursts which represent one type of the most critical mining disasters in underground coal mines. To evaluate coal burst risks ...and comprehend the response of the coal-rock mass to seismic waves, microseismic monitoring stands as the principal method. By inferring the zones with elevated coal burst risks based on the seismic event clusters, valuable insights can be gained. However, because of limited seismic monitoring results generated from an individual seismic event, the recognition of the corresponding dynamic disturbance process remains ambiguous. The dynamic disturbance process presents immense complexity due to the focal mechanism and heterogeneous medium, particularly under the effect of structural heterogeneity induced by large-scale mining operations. In this study, forward numerical modelling was employed to gain the comprehension of seismic wave propagation affected by extraction zones. The findings revealed heightened intricacy of the wavefields and increased displacement concentrations around the working face. The characteristics of peak particle velocity (PPV) and displacement spectra were investigated in the near- and far-field zones, respectively. Owing to the existence of the extraction zone, both a significant amplification effect and the redistribution of PPV were observed around the near-field zone. The intricate wavefield caused by the focal mechanism and extraction zones resulted in more scattered distributions of the low-frequency spectral level, which can potentially cause an overestimation of source intensity. However, the impact of the complex wavefield on the corner frequency was limited. Through the analysis of the PPV attenuation law, as well as the distribution of both seismic moment and source radius, this study offered valuable insights for seismic risk assessment. The forward modelling approach facilitated the identification of high-risk potential areas resulting from seismic events, which deepened our comprehension of the dynamic disturbance process in the complex underground mine environment.
In selective autophagy, receptors are central for cargo selection and delivery. However, it remains yet unclear whether and how multiple autophagy receptors might form complex and function ...concertedly to control autophagy. Optineurin (OPTN), implicated genetically in glaucoma and amyotrophic lateral sclerosis, was a recently identified autophagy receptor. Here we report that tumor-suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux. Interestingly, the Lys48-linked polyubiquitin chains that HACE1 conjugates onto OPTN might predominantly target OPTN for autophagic degradation. By demonstrating that the HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells, our findings may open an avenue for developing autophagy-targeted therapeutic intervention into cancer.
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•HACE1 mediates ubiquitylation of autophagy receptor OPTN in vitro and in vivo•HACE1-ubiquitylated OPTN interacts with p62 to form autophagy receptor complex•Lys48-linked polyubiquitin chains on OPTN target it for autophagic degradation•HACE1 and OPTN constitute an axis to activate autophagy and suppress tumor
Liu et al. report that HACE1 ubiquitylates Optineurin (OPTN) and promotes autophagy by facilitating autophagy receptor-complex formation involving OPTN and p62/SQSTM1. The HACE1-OPTN axis suppresses growth and tumorigenicity of lung cancer cells, suggesting activating autophagy as a potential therapeutic approach.
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