Constrained Bayesian Optimization with Adaptive Active Learning of Unknown Constraints

Optimizing objectives under constraints, where both the objectives and constraints are black box functions, is a common scenario in real-world applications such as scientific experimental design, design of medical therapies, and industrial process optimization. One popular approach to handling these complex scenarios is Bayesian Optimization (BO). In terms of theoretical behavior, BO is relatively well understood in the unconstrained setting, where its principles have been well explored and validated. However, when it comes to constrained Bayesian optimization (CBO), the existing framework often relies on heuristics or approximations without the same level of theoretical guarantees. In this paper, we delve into the theoretical and practical aspects of constrained Bayesian optimization, where the objective and constraints can be independently evaluated and are subject to noise. By recognizing that both the objective and constraints can help identify high-confidence regions of interest (ROI), we propose an efficient CBO framework that intersects the ROIs identified from each aspect to determine the general ROI. The ROI, coupled with a novel acquisition function that adaptively balances the optimization of the objective and the identification of feasible regions, enables us to derive rigorous theoretical justifications for its performance. We showcase the efficiency and robustness of our proposed CBO framework through empirical evidence and discuss the fundamental challenge of deriving practical regret bounds for CBO algorithms

Recruitment of O-GlcNAc Transferase to Promoters by Corepressor mSin3A Coupling Protein O-GlcNAcylation to Transcriptional Repression

AbstractTranscription factors and RNA polymerase II can be modified by O-linked N-acetylglucosamine (O-GlcNAc) monosaccharides at serine or threonine residues, yet the precise functional roles of this modification are largely unknown. Here, we show that O-GlcNAc transferase (OGT), the enzyme that catalyzes this posttranslational modification, interacts with a histone deacetylase complex by binding to the corepressor mSin3A. Functionally, OGT and mSin3A cooperatively repress transcription in parallel with histone deacetylation. We propose that mSin3A targets OGT to promoters to inactivate transcription factors and RNA polymerase II by O-GlcNAc modification, which acts in concert with histone deacetylation to promote gene silencing in an efficient and specific manner

Performance Assessment of Solar Assisted Absorption Heat Pump System with Parabolic Trough Collectors

AbstractA solar assisted absorption heat pump (AHP) system was installed in Tianjin University for space heating in winter and heat water supply. The primary heat source for the AHP is supplied from parabolic trough collectors. In this paper, experimental and simulation are presented to give an overview assessment of the whole system. The performance of the solar collectors in steady and transient state was investigated, the thermal efficiency curve that characterizing the optical and heat loss of the collectors was carried out with a series of tests. For the whole system, the absorption heat pump performance during operating test was measured and presented.The simulation were performed by TRNSYS using the measured meteorological data and the estimated building load with the specific building type and structure, the daily and monthly operation showed that the solar radiation had significant impact on the ratio of useful energy provided by solar collectors, a high instantaneous solar fraction during the sunshine time while a very low average daily solar fraction was seen from the simulation results, this indicated that a thermal storage is necessary to improve the system performance and lower the auxiliary energy usage

Effects of Climate Warming on Net Primary Productivity in China During 1961–2010

The response of ecosystems to different magnitudes of climate warming and corresponding precipitation changes during the last few decades may provide an important reference for predicting the magnitude and trajectory of net primary productivity (NPP) in the future. In this study, a process-based ecosystem model, Carbon Exchange between Vegetation, Soil and Atmosphere (CEVSA), was used to investigate the response of NPP to warming at both national and subregional scales during 1961–2010. The results suggest that a 1.3°C increase in temperature stimulated the positive changing trend in NPP at national scale during the past 50 years. Regardless of the magnitude of temperature increase, warming enhanced the increase in NPP; however, the positive trend of NPP decreased when warming exceeded 2°C. The largest increase in NPP was found in regions where temperature increased by 1–2°C, and this rate of increase also contributed the most to the total increase in NPP in China\u27s terrestrial ecosystems. Decreasing precipitation depressed the positive trend in NPP that was stimulated by warming. In northern China, warming depressed the increasing trend of NPP and warming that was accompanied by decreasing precipitation led to negative changing trends in NPP in large parts of northern China, especially when warming exceeded 2°C. However, warming stimulated the increase in NPP until warming was greater than 2°C, and decreased precipitation helped to increase the NPP in southern China

Differentiation of canine distemper virus isolates in fur animals from various vaccine strains by reverse transcription-polymerase chain reaction-restriction fragment length polymorphism according to phylogenetic relations in china

In order to effectively identify the vaccine and field strains of Canine distemper virus (CDV), a new differential diagnostic test has been developed based on reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). We selected an 829 bp fragment of the nucleoprotein (N) gene of CDV. By RFLP analysis using BamHI, field isolates were distinguishable from the vaccine strains. Two fragments were obtained from the vaccine strains by RT-PCR-RFLP analysis while three were observed in the field strains. An 829 nucleotide region of the CDV N gene was analyzed in 19 CDV field strains isolated from minks, raccoon dogs and foxes in China between 2005 and 2007. The results suggest this method is precise, accurate and efficient. It was also determined that three different genotypes exist in CDV field strains in fur animal herds of the north of China, most of which belong to Asian type. Mutated field strains, JSY06-R1, JSY06-R2 and JDH07-F1 also exist in Northern China, but are most closely related to the standard virulent strain A75/17, designated in Arctic and America-2 genetype in the present study, respectively

Engineering Scheffersomyces segobiensis for palmitoleic acid‐rich lipid production

Palmitoleic acid (POA; C16:1) is an essential high- value ω- 7- conjugated fatty acid with beneficial bioactivities and potential applications in the nu-traceutical and pharmaceutical industries. Previously, the oleaginous yeast Scheffersomyces segobiensis DSM27193 has been identified as a promis-ing production host as an alternative for POA extraction from plant or animal sources. Here, the POA-producing capacity of this host was further expanded by optimizing the fermentation process and molecular strain engineering. Specifically, a dual fermentation strategy (O-S dynamic regulation strategy) focused on the substrate and dissolved oxygen concentration was designed to eliminate ethanol and pyruvate accumulation during fermentation. Key genes influencing POA production, such as jen, dgat, ole were identified on the transcriptional level and were subsequently over-expressed. Furthermore, the phosphoketolase (Xpk)/phosphotransacetylase (Pta) pathway was intro-duced to improve the yield of the precursor acetyl-CoA from glucose. The resulting cell factory SS-12 produced 7.3 g/L of POA, corresponding to an 11-fold increase compared to the wild type, presenting the highest POA titre reported using oleaginous yeast to date. An economic evaluation based on the raw materials, utilities and facility-dependent costs showed that microbial POA production using S. segobiensis can supersede the current extraction method from plant oil and marine fish. This study reports the construction of a promising cell factory and an effective microbial fermentation strategy for commercial POA production

O-GlcNAc Modification Is an Endogenous Inhibitor of the Proteasome

AbstractThe ubiquitin proteasome system classically selects its substrates for degradation by tagging them with ubiquitin. Here, we describe another means of controlling proteasome function in a global manner. The 26S proteasome can be inhibited by modification with the enzyme, O-GlcNAc transferase (OGT). This reversible modification of the proteasome inhibits the proteolysis of the transcription factor Sp1 and a hydrophobic peptide through inhibition of the ATPase activity of 26S proteasomes. The Rpt2 ATPase in the mammalian proteasome 19S cap is modified by O-GlcNAc in vitro and in vivo and as its modification increases, proteasome function decreases. This mechanism may couple proteasomes to the general metabolic state of the cell. The O-GlcNAc modification of proteasomes may allow the organism to respond to its metabolic needs by controlling the availability of amino acids and regulatory proteins

Network Pharmacology-Based Validation of Caveolin-1 as a Key Mediator of Ai Du Qing Inhibition of Drug Resistance in Breast Cancer

Chinese formulas have been paid increasing attention in cancer multidisciplinary therapy due to their multi-targets and multi-substances property. Here, we aim to investigate the anti-breast cancer and chemosensitizing function of Ai Du Qing (ADQ) formula made up of Hedyotis diffusa, Curcuma zedoaria (Christm.) Rosc., Astragalus membranaceus (Fisch.) Bunge, and Glycyrrhiza uralensis Fisch. Our findings revealed that ADQ significantly inhibited cell proliferation in both parental and chemo-resistant breast cancer cells, but with little cytotoxcity effects on the normal cells. Besides, ADQ was found to facilitate the G2/M arresting and apoptosis induction effects of paclitaxel. Network pharmacology and bioinformatics analysis further demonstrated that ADQ yielded 132 candidate compounds and 297 potential targets, and shared 22 putative targets associating with breast cancer chemoresponse. Enrichment analysis and experimental validation demonstrated that ADQ might improve breast cancer chemosensitivity via inhibiting caveolin-1, which further triggered expression changes of cell cycle-related proteins p21/cyclinB1 and apoptosis-associated proteins PARP1, BAX and Bcl-2. Besides, ADQ enhanced in vivo paclitaxel chemosensitivity on breast cancer. Our study not only uncovers the novel function and mechanisms of ADQ in chemosensitizing breast cancer at least partly via targeting caveolin-1, but also sheds novel light in utilizing network pharmacology in Chinese Medicine research