Mitigating Semantic Confusion from Hostile Neighborhood for Graph Active Learning

Graph Active Learning (GAL), which aims to find the most informative nodes in graphs for annotation to maximize the Graph Neural Networks (GNNs) performance, has attracted many research efforts but remains non-trivial challenges. One major challenge is that existing GAL strategies may introduce semantic confusion to the selected training set, particularly when graphs are noisy. Specifically, most existing methods assume all aggregating features to be helpful, ignoring the semantically negative effect between inter-class edges under the message-passing mechanism. In this work, we present Semantic-aware Active learning framework for Graphs (SAG) to mitigate the semantic confusion problem. Pairwise similarities and dissimilarities of nodes with semantic features are introduced to jointly evaluate the node influence. A new prototype-based criterion and query policy are also designed to maintain diversity and class balance of the selected nodes, respectively. Extensive experiments on the public benchmark graphs and a real-world financial dataset demonstrate that SAG significantly improves node classification performances and consistently outperforms previous methods. Moreover, comprehensive analysis and ablation study also verify the effectiveness of the proposed framework.Comment: Accepted by CIKM 202

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo

Targeted protein degradation offers an alternative modality to classical inhibition and holds the promise of addressing previously undruggable targets to provide novel therapeutic options for patients. Heterobifunctional molecules co-recruit a target protein and an E3 ligase, resulting in ubiquitylation and proteosome-dependent degradation of the target. In the clinic, the oral route of administration is the option of choice but has only been achieved so far by CRBN- recruiting bifunctional degrader molecules. We aimed to achieve orally bioavailable molecules that selectively degrade the BAF Chromatin Remodelling complex ATPase SMARCA2 over its closely related paralogue SMARCA4, to allow in vivo evaluation of the synthetic lethality concept of SMARCA2 dependency in SMARCA4-deficient cancers. Here we outline structure- and property-guided approaches that led to orally bioavailable VHL-recruiting degraders. Our tool compound, ACBI2, shows selective degradation of SMARCA2 over SMARCA4 in ex vivo human whole blood assays and in vivo efficacy in SMARCA4-deficient cancer models. This study demonstrates the feasibility for broadening the E3 ligase and physicochemical space that can be utilised for achieving oral efficacy with bifunctional molecules

Eco-economic performance and application potential of a novel dual-source heat pump heating system

Decarbonization of building heating is the key to carbon neutrality. Heat pumps have great potential to replace non-renewable heating devices, thus creating economic and renewable heating systems. To overcome the application challenges of conventional heat pumps (HP), a novel dual-source heat pump (DSHP) heating system and corresponding model are proposed and validated in this paper. Simulated by the validated experiment-based model, the performance of the DSHP heating system is numerically investigated by comparing with different systems in various regions. The results show that the DSHP system has higher seasonal performance factors and near-zero defrosting costs when compared to the conventional HP heating system in different regions, resulting in 1.88%–21.53% reductions in annual heating bills and carbon emissions. Compared to the gas boiler heating system, the DSHP system can achieve 20.64%–54.36% of annual heating bill savings and 14.39%–86.09% of annual carbon reductions in selected regions. The investigation of heating characteristics and eco-economic performance of the DSHP system in different regions provided important guiding significance for the DSHP in global application, and thus contributes to achieving bill-saving and low-carbon heating and sustainable development

Muscle to Brain Partitioning as Measure of Transporter-Mediated Efflux at the Rat Blood–Brain Barrier and Its Implementation into Compound Optimization in Drug Discovery

Movement of xenobiotic substances across the blood–brain barrier (BBB) is tightly regulated by various transporter proteins, especially the efflux transporters P-glycoprotein (P-gp/MDR1) and breast cancer resistance protein (BCRP). Avoiding drug efflux at the BBB is a unique challenge for the development of new central nervous system (CNS) drugs. Drug efflux at the BBB is described by the partition coefficient of unbound drug between brain and plasma (Kp,uu,brain) which is typically obtained from in vivo and often additionally in vitro measurements. Here, we describe a new method for the rapid estimation of the in vivo drug efflux at the BBB of rats: the measurement of the partition coefficient of a drug between brain and skeletal muscle (Kp,brain/muscle). Assuming a closely similar distribution of drugs into the brain and muscle and that the efflux transporters are only expressed in the brain, Kp,brain/muscle, similar to Kp,uu,brain, reflects the efflux at the BBB. The new method requires a single in vivo experiment. For 64 compounds from different research programs, we show the comparability to other approaches used to obtain Kp,uu,brain. P-gp- and BCRP-overexpressing cell systems are valuable in vitro tools for prescreening. Drug efflux at the BBB can be most accurately predicted based on a simple algorithm incorporating data from both in vitro assays. In conclusion, the combined use of our new in vivo method and the in vitro tools allows an efficient screening method in drug discovery with respect to efflux at the BBB

GVoS:A General System for Near-Duplicate Video-Related Applications on Storm

The exponential increase of online videos greatly enriches the life of users but also brings huge numbers of near-duplicate videos (NDVs) that seriously challenge the video websites. The video websites entail NDV-related applications such as detection of copyright violation, video monitoring, video re-ranking, and video recommendation. Since these applications adopt different features and different processing procedures due to diverse scenarios, constructing separate and special-purpose systems for them incurs considerable costs on design, implementation, and maintenance. In this article, we propose a general NDV system on Storm (GVoS)—a popular distributed real-time stream processing platform—to simultaneously support a wide variety of video applications. The generality of GVoS is achieved in two aspects. First, we extract the reusable components from various applications. Second, we conduct the communication between components via a mechanism called Stream Shared Message (SSM) that contains the video-related data. Furthermore, we present an algorithm to reduce the size of SSM in order to avoid the data explosion and decrease the network latency. The experimental results demonstrate that GVoS can achieve performance almost the same as the customized systems. Meanwhile, GVoS accomplishes remarkably higher systematic versatility and efficiently facilitates the development of various NDV-related applications.</jats:p

Genetic Analysis of Diversity within a Chinese Local Sugarcane Germplasm Based on Start Codon Targeted Polymorphism

In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic diversity among 107 sugarcane accessions within a local sugarcane germplasm collection. These primers amplified 176 DNA fragments, of which 163 were polymorphic (92.85%). Polymorphic information content (PIC) values ranged from 0.783 to 0.907 with a mean of 0.861. Unweighted pair group method of arithmetic averages (UPGMA) cluster analysis of the SCoT marker data divided the 107 sugarcane accessions into six clusters at 0.674 genetic similarity coefficient level. Relatively abundant genetic diversity was observed among ROC22, ROC16, and ROC10, which occupied about 80% of the total sugarcane acreage in China, indicating their potential breeding value on Mainland China. Principal component analysis (PCA) partitioned the 107 sugarcane accessions into two major groups, the Domestic Group and the Foreign Introduction Group. Each group was further divided based on institutions, where the sugarcane accessions were originally developed. The knowledge of genetic diversity among the local sugarcane germplasm provided foundation data for managing sugarcane germplasm, including construction of a core collection and regional variety distribution and subrogation

A Bidirectional Permeability Assay for beyond Rule of 5 Compounds

Bidirectional permeability measurement with cellular models grown on Transwell inserts is widely used in pharmaceutical research since it not only provides information about the passive permeability of a drug, but also about transport proteins involved in the active transport of drug substances across physiological barriers. With the increasing number of investigative drugs coming from chemical space beyond Lipinski’s Rule of 5, it becomes more and more challenging to provide meaningful data with the standard permeability assay. This is exemplified here by the difficulties we encountered with the cyclic depsipeptides emodepside and its close analogs with molecular weight beyond 1000 daltons and cLogP beyond 5. The aim of this study is to identify potential reasons for these challenges and modify the permeability assays accordingly. With the modified assay, intrinsic permeability and in vitro efflux of depsipeptides could be measured reliably. The improved correlation to in vivo bioavailability and tissue distribution data indicated the usefulness of the modified permeability assay for the in vitro screening of compounds beyond the Rule of 5