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

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

Complete genome sequence and pathogenesis of bovine viral diarrhea virus JL-1 isolate from cattle in China

BACKGROUND: Bovine viral diarrhea virus (BVDV) is a pathogen found worldwide in calves. It can cause significant economic losses in agriculture. Many BVDV strains have been isolated in China. However, the pathogenesis and complete gene characteristics of BVDV isolate have yet not been reported in China. Here, a BVDV isolate was isolated and its pathogenesis and complete genome were studied. RESULTS: A new isolate of bovine viral diarrhea virus, named JL-1, was isolated from the spleen of a sick cow with diarrhea using MDBK cell culture. The complete genome of JL-1 is 12,276 nucleotides and contains a 5′-UTR of 382 nucleotides, a 3′-UTR of 188 nucleotides, and a large ORF encoding a polyprotein consisting of 3,901 amino acids. Genomic comparison and phylogenetic analyses of complete genomic sequence clearly showed that JL-1 fell into the BVDV-1b subtype. The result of pathogenesis of JL-1 strain showed that all infected calves developed clinical signs of elevated rectal temperatures, decreased leucopenia, and viral discharge. Viral antigen was detected in infected animal tissues using immunohistochemistry. Animals in the mock were normal. These results demonstrated that BVDV JL-1 was a virulent strain. CONCLUSIONS: This is the first study to report the pathogenesis and complete gene characterization of the BVDV strain in China. This report may set a good foundation for further study of BVDV in China

The efficacy and safety of adjuvant immunotherapy after neoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal squamous cell carcinoma: a real−world study

BackgroundThe promising therapeutic outcomes of neoadjuvant immunotherapy with chemotherapy (NAIC) in the treatment of resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have been confirmed by several clinical trials. However, the potential benefits of adjuvant therapy for LA-ESCC patients remain unclear.Materials and methodsWe analyzed the LA-ESCC patients underwent NAIC and adjuvant immunotherapy between January 2020 and September 2023. The effectiveness and feasibility of adjuvant immunotherapy were evaluated.ResultsA total of 112 LA-ESCC patients were included. With a median follow-up of 24.0 months, all 112 patients had an R0 resection, and 23 patients (20.5%) achieved pathological complete response (pCR). The median disease-free survival (DFS) and overall survival (OS) were 18.5 and 24.0 months. The 12- and 24-month DFS rates were 91.0% and 81.7%, and the 12- and 24-month OS rates were 99.1% and 96.8%, respectively. Patients with BMI ≥20 kg/m2 had a longer 24-month DFS rate compared with those with BMI <20 kg/m2 (87.1% vs 62.0%, P=0.034). Additionally, patients with postoperative pCR than those with non-pCR achieved better 12-month (100% vs 88.6%) and 24-month (100% vs 77.3%, P<0.001) DFS. Superior DFS rates were acquired in patients with ypT0-1 (12-month: 98.1% vs 84.6%, P=0.008, 24-month: 95.4% vs 70.7%, P<0.001), ypN0 (12-month: 96.9% vs 83.1%, P=0.019, 24-month: 88.9% vs 72.2%, P=0.042), obtained T (12-month: 96.2% vs 78.3%, P=0.018, 24-month: 92.8% vs 56.0%, P<0.001) or TNM (12-month: 96.5% vs 84.8%, P=0.033, 24-month: 90.5% vs 72.5%, P=0.02) downstaging. A total of 85 (78.0%) patients experienced treatment-related adverse events (TRAEs), with the most common TRAEs were digestive reactions (52.3%) and neutropenia (50.4%). The majority of these events were classified as grade 1-2.ConclusionThe combination of NAIC and adjuvant immunotherapy displays short survival benefits and has an acceptable safety profile, which may be an effective treatment strategy for LA-ESCC patients

Relationship between triglyceride glucose-body mass index baselines and variation with future cardiovascular diseases risk in the middle-aged and elderly individuals

BackgroundCardiovascular diseases (CVDs) are gradually becoming the leading cause of morbidity and mortality among chronic non-communicable diseases. Previous studies have found that the TyG index is an effective alternative indicator for insulin resistance (IR) and is associated with cardiovascular events. Additionally, obesity directly or indirectly increases the risk of developing CVDs. Up to now, studies on the combined effects of these factors are insufficient, and the conclusions are not yet consistent. This study aims to analyze whether the baseline levels and fluctuations of triglyceride glucose-body mass index (TyG-BMI) are associated with the incidence of CVDs and their subtypes in a prospective cohort of middle-aged and elderly individuals.MethodsThe data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. After excluding participants with partially missing variables that could affect the study results, this study ultimately included 7,072 participants, with data records spanning from 2011 to 2020. The exposures were TyG-BMI and the change in TyG-BMI from 2011 to 2015. The TyG-BMI index was calculated as TyG index multiply BMI. The change of TyG-BMI was categorized using K-means clustering and baseline TyG-BMI was grouped based on quartiles. We used Cox proportional hazards models to evaluate the relationship between baseline quartiles of the TyG-BMI index and its variability with CVDs and their subtypes.ResultsAmong the 7,072 participants (mean age of 59.1 ± 9.3 years), 3330 (47%) were male. During an average follow-up of 7.1 years, 1,774 (25.1%) participants developed new-onset cardiovascular diseases. After stratification by baseline TyG-BMI quartiles, higher TyG-BMI levels were associated with an increased risk of CVDs, The hazard ratio (HR) and 95% confidence interval (95% CI) for the highest quartile group were 1.69 (1.44-2.00). After adjusting for potential confounding factors, compared to participants with consistently low TyG-BMI levels, those with moderate TyG-BMI levels and a slowly increasing trend had an HR of 1.27 (95% CI 1.10-1.47), while those with the highest TyG-BMI levels and a slowly decreasing trend had an HR of 1.52 (95% CI 1.26-1.83).ConclusionMaterial changes in the TyG-BMI are independently associated with the risk of CVDs in middle-aged and elderly individuals. Detecting long-term changes in the TyG-BMI may aid in the early identification of high-risk individuals and help prevent the occurrence of various cardiovascular diseases