【PaperReading】Prevalence and patterns of higher-order drug interactions in Escherichia coli

研究发现,随着应用于大肠杆菌的抗生素组合数量的增加,高阶药物相互作用(三药、四药和五药组合)的频率显著增加,与之前的假设相反。这些相互作用不仅包括净协同作用(效果大于预期),还显示出紧急拮抗作用(效果低于预期)的增加。这些发现强调了在设计药物组合时考虑高阶相互作用的重要性,以对抗复杂疾病的治疗,如抗生素耐药性。

Prevalence and patterns of higher-order drug interactions in Escherichia coli

 

大肠杆菌中高阶药物相互相互作用模式和普遍性

Elif TekinCynthia WhiteTina Manzhu Kang

内容概要:本文详细介绍了“秒杀商城”微服务架构的设计与实战全过程,涵盖系统从需求分析、服务拆分、技术选型到核心功能开发、分布式事务处理、容器化部署及监控链路追踪的完整流程。重点解决了高并发场景下的超卖问题,采用Redis预减库存、消息队列削峰、数据库乐观锁等手段保障数据一致性,并通过Nacos实现服务注册发现与配置管理,利用Seata处理跨服务分布式事务,结合RabbitMQ实现异步下单,提升系统吞吐能力。同时,项目支持Docker Compose快速部署和Kubernetes生产级编排,集成Sleuth+Zipkin链路追踪与Prometheus+Grafana监控体系,构建可观测性强的微服务系统。; 适合人群:具备Java基础和Spring Boot开发经验,熟悉微服务基本概念的中高级研发人员,尤其是希望深入理解高并发系统设计、分布式事务、服务治理等核心技术的开发者;适合工作2-5年、有志于转型微服务或提升架构能力的工程师; 使用场景及目标:①学习如何基于Spring Cloud Alibaba构建完整的微服务项目;②掌握秒杀场景下高并发、超卖控制、异步化、削峰填谷等关键技术方案;③实践分布式事务(Seata)、服务熔断降级、链路追踪、统一配置中心等企业级中间件的应用;④完成从本地开发到容器化部署的全流程落地; 阅读建议:建议按照文档提供的七个阶段循序渐进地动手实践,重点关注秒杀流程设计、服务间通信机制、分布式事务实现和系统性能优化部分,结合代码调试与监控工具深入理解各组件协作原理,真正掌握高并发微服务系统的构建能力。
Stage-based Neural Network for Reflow Profile Prediction and Reflow Recipe Optimization for Quality and Energy Saving Zhenxuan Zhang1, Yuanyuan Li1, Sang Won Yoon1, Daehan Won1* 1*System Science and Industry Engineering, State University of the New York at Binghamton, Binghamton, 13902, NY, United States. *Corresponding author(s). E-mail(s): dhwon@binghamton.edu; Contributing authors: zzhang98@binghamton.edu; yli352@binghamton.edu; yoons@binghamton.edu; Abstract During the reflow process, solder joints are formed on the boards with the placed components, so the temperature settings in the reflow oven chamber are vital to the quality of the PCB. Inappropriate profiles cause various defects such as cracks, bridging, delamination, etc. Solder paste manufacturers have generally provided the ideal thermal profile (i.e., target profile), and PCB manufacturers have attempted to meet the given profile by fine-tuning the oven’s recipe. The conventional method tunes the recipe to gather thermal data with a thermal measurement device. It adjusts the profile, which relies on the trial-and-error method which takes much time and effort. This paper proposes (1) a recipe initialization method for determining the initial recipe for collecting training data, (2) a stage-based (ramp, soak, and reflow) input data segmentation method for data preprocessing, (3) a backpropagation neural network, (BPNN) model for predicting the required zone temperature to reduce the gap between the actual processing profile and the target profile, (4) a mixed-integer linear programming (MILP) algorithm for generates the optimal recipe to minimize the temperature settings. This paper aims to enable non-contact prediction of required air temperature from one experiment. The MILP optimization model utilized the constraints of the upper and lower bounds obtained from the prediction result. The model has been cross-validated with different initial recipes and different target profiles. As a result, within 10 minutes of starting the experiment, the generated optimal recipe improved the fitness to the targeted profile by 4.2%, which resulted in 99% and, in the meanwhile, lowered the energy cost by 23%. Keywords: reflow thermal recipe optimization, machine learning, stage-based segmentation, backpropagation neural network (BPNN), mixed-integer linear programming (MILP). 1 1 Introduction After solder paste printing and components are picked and placed, the soldering reflow process (SRP) is the final process on the surface mount technology assembly line. The SRP is of utmost importance as part of the SMT assembly line process [1]. Meanwhile, the reflow process is also the most critical part of the green manufacturing concept because the process requirement of the reflow process has an acceptable range in the key features of the reflow profile (temperature curve). Thus, the energy consumption can be different for multiple candidate target profiles, which have different energy consumption levels. To optimize the reflow process, the fitness of the actual reflow profile and the target profile needs to be considered. Additionally, energy consumption should be optimized. The combination of the temperature settings of the heating zones in the reflow oven controls the reflow profiles. In the SRP process, several processes are involved, which include ramping, soaking, reflow, and cooling. The printed solder paste melts into a liquid to connect the copper pads and the component joints during the heating period. It becomes solid and forms solder joints during the cooling period. A target thermal profile (temperature curve) is usually recommended by the manufacturer based on the physical properties of each solder paste, which results in an ideal solder joint. Fig. 1 shows the target thermal profile for Indium 8.9HF Pb-free SAC305 (96.5% Sn, 3.0% Ag, and 0.5% Cu) solder paste, used in this research. The entire SRP includes four stages: ramping, soaking, reflow, and cooling. The target thermal profile has some key features, which include the climbing slope liquidus temperature, which is 220◦C. The target peak temperature is 240◦C, as shown in the Fig. 1, with an acceptable range of 220 − 260◦C. The target time above liquidus (TAL) is 60 seconds, with an acceptable range of 30-120. The optimized reflow recipe should satisfy the target values of the features if not within the recommended or acceptable ranges. This research aims to (1) identify the required air temperature range for the zones in the reflow oven to fit the target thermal profile using a backpropagation neural network (BPNN); (2) optimize the reflow recipe to minimize the energy consumption from the candidate recipes using MILP. The comparable study proved that the reflow profile is highly related to the long-term reliability of the solder joints [2]. The reflow profile has better fitness to the target profile and outperforms in terms of long-term reliability [3]. The solder paste manufacturer suggests the target profile, the tested outperforming reflow profile. Thus, the reflow recipe that approaches a high fitness to the target profile can optimize solder joint long-term reliability. The experimental profile is obtained from the k-type thermocouples, which are attached to the solder joints, and a non-contact prediction model proposed by the previous research [4] is used to predict the solder joint temperature to improve the testing efficiency and reduce the redundancy of experiments and by comparison of the predicted thermal 2 Fig. 1 Target profile of Indium 8.9HF SAC305 Pb-free solder paste profile and the target profile, the result can also be regarded as an evaluation method of the oven status in real-time for quality control. The main determinant of a thermal profile is the environment inside the reflow oven. Heller 1707MKEV forced convection reflow oven is used in this study, which contains seven heating zones, followed by one cooling zone. Based on the test results, one of the studies shows that heat transfer coefficients differ between periods [5]. In this study, the heat transfer coefficients are calculated separately for each zone. In this research, the required temperature-adjustable range (upper and lower bounds) of the reflow recipe for each of the 7 zones can be obtained within one iteration using ANN. The model works well with the data collected from any random initial recipe and can be applied to different target thermal profiles. To evaluate the reflow energy cost of the recipe, the reflow energy index (REI) was proposed, and an optimization model using MILP was used to obtain the optimal reflow recipe. This study is extended from tentative research we previously published [18]. The remainder of this article is organized as follows: Section 2 introduces related literature; Section 3 discusses the proposed methods in this research; Section 4 contains the experiment material, parameter settings, and results; and Section 5 considers conclusions and future work. 2 Literature Review The SRP-related publications are described in this section. The thermal profile simulation of the solder joint during SRP in the SMT assembly line has been widely studied in 2 major directions. The first one is using the physics-based model, including computational fluid 3 dynamics (CFD), finite element (FE), and finite difference (FD). The other one is the data driven approaches, especially with machine learning (ML) and artificial intelligence (AI) [6]. As far as physics-based models are concerned, FD is most commonly used to solve differential equations that govern the flow of fluid in order to simulate the thermal behavior of fluids [7, 8]. Mathematical solutions to complex equations can be obtained through the application of FE and FD techniques [6]. Several studies have demonstrated that these methods are capable of producing reliable and accurate results from simulations since the simulation results are derived from the model constructed using the physics equations [9]. Meanwhile, the disadvantage of the physics-based model is notably significant since such models require intermediate knowledge of physics equations as well as field-specific knowledge [10]. The data-driven approach, on the other hand, has the advantage of being less dependent on physics, which contributes to better generalizability, as well as improved computational efficiency [11]. In contrast to physics-based simulations, which always produce the results of a perfect environment, the data-driven model can capture the general pattern of a real-production experimental environment based on experimental data and can be compared to the data-driven model projected into the future [12]. As for the data-driven AI approaches, multiple approaches have been proposed from comparable research using numerical simulation. A simulation function was realized from a different perspective by developing equations relating to the heat transfer process. The data driven AI approach requires experimentation, and according to the experiment-based studies used in this research, the characteristics of the PCB boards and components affect heat transfer activities. The time to reach the melting point on the solder paste has a linear relationship with the thickness of the board [19, 20]. Thinner boards have larger heating factors, which can be heated up and cooled down faster, which has a higher peak temperature under the same recipe settings [21]. The thermal profile was utilized to develop a mathematical simulation model that accurately predicted solvent loss during the heating process [13] and achieved excellent simulation results. During multiple impinging jets in solder reflow, a mathematical model has been developed to predict surface temperatures, which are closely matched by the predicted surface temperatures [14]. The increasing prevalence of large data sets is giving rise to the use of Artificial Intelligence and Machine Learning (ML) to obtain classification and prediction functions in many fields. For the ML approaches in the reflow setting optimization studies, multiple approaches were used, i.e., artificial neural networks (ANN), non-linear programming (NLP), and genetic algorithm (GA) [15, 16, 22–24]. From the comparative studies, heating factor Qn is presented as a comprehensive formulation of the two parameters, the peak temperature Tp and the time above liquidus (TAL) [22, 23]. With the heating factor, the BPNN, one of the ANN approaches, was introduced to describe the non-linear relationship between the recipe settings and the reflow thermal profiles [18]. By inputting factors such as soak time, reflow time, and peak temperature in the SMT domain, ANNs were also applied to predict and optimize with high 4 accuracy obtained [22]. ANN has many advantages, including the ability to handle non-linear data with high generalization capability. The ANN models are widely used due to their capability of handling multiple-inputmultiple-output (MIMO) problems, which also offer the advantage of fitting complex non-linear relationships with low requirements of data format and knowledge of data [1, 15, 16]. Additionally, ANN was developed to predict the tolerance for shear forces in reflowed solder joints by taking into account factors such as soak time, reflow time, and peak temperature. As a result of the predictions, it was determined that the experimental shear force was highly accurate [16]. As compared to the high accuracy performance of the ANN approach, the computational cost of deep-learning approaches is significantly higher than that of data-driven machine-learning approaches [4]. It has been proposed that artificial neural networks be combined with physical equations to develop a hybrid artificial intelligence model that can accurately predict the thermal profile and temperature. Artificial intelligence-based methods have the advantage of being efficient and performing well. In addition to the drawbacks of all the physicsbased approaches, hybrid AI models require higher levels of physics knowledge, which is also inefficient from a computational perspective. Furthermore, regression-based methods of machine learning and artificial intelligence-based methods were incorporated. For example, a regression model trained using experimental data would be able to simulate the thermal profile during a solder reflow process. The optimal thermal profile was determined by utilizing a simulation model to determine a number of heat factor values based on a well-shaped thermal profile [17]. The regression-based methods have the advantage of computational efficiency but, in exchange, have a lower level of accuracy. Since this study focuses on obtaining the maximum fitness to the target reflow profile and then minimizing the energy cost, an improved version of BPNN was proposed to get the adjustable range of the recipe settings. Then, the mixed-integer linear programming (MILP) approach was used rather than the NLP approach in comparable studies. This would be beneficial in lowering computational complexity.
08-10
这篇论文提出了一种基于阶段划分的神经网络和混合整数线性规划(MILP)相结合的方法,用于回流焊热曲线预测与工艺优化,旨在提高产品质量并降低能耗。下面我将从模型设计、实现方法以及关键算法三个方面进行解析。 --- ## 一、模型设计:阶段划分的BPNN神经网络 论文提出了一种**阶段划分式输入数据预处理方法**,将回流焊过程划分为三个阶段: - **Ramp(升温段)** - **Soak(保温段)** - **Reflow(回流段)** 这种划分方式有助于模型更好地捕捉不同阶段对最终热曲线的影响。接着,作者使用**反向传播神经网络(BPNN)**来预测每个加热区的温度设置,以逼近目标热曲线。 ### Python实现示例(简化版BPNN模型): ```python import numpy as np from sklearn.neural_network import MLPRegressor from sklearn.model_selection import train_test_split # 模拟数据:每个样本包含三个阶段的输入特征(例如时间、设定温度等) # X.shape = (n_samples, n_features) # y.shape = (n_samples, n_zones) # 每个样本对应7个加热区的目标温度 X = np.random.rand(1000, 9) # 3阶段 × 3个特征 y = np.random.rand(1000, 7) # 划分训练集与测试集 X_train, X_test, y_train, y_test = train_test_split(X, y, test_size=0.2) # 构建BPNN模型 model = MLPRegressor(hidden_layer_sizes=(64, 64), max_iter=1000, solver='adam', activation='relu') # 训练模型 model.fit(X_train, y_train) # 预测 predicted_zones = model.predict(X_test) ``` ### 代码解释: - 使用`MLPRegressor`构建了一个具有两个隐藏层的BPNN网络,用于预测7个加热区的温度。 - 输入数据`X`是根据三个阶段划分的特征数据。 - 输出`y`为每个加热区的目标温度设置。 - 该模型可以用于预测新实验条件下所需的温度设置。 --- ## 二、优化方法:混合整数线性规划(MILP) 在预测出加热区温度范围后,论文进一步使用**混合整数线性规划(MILP)**来优化最终的回流焊配方,目标是最小化能耗(REI:Reflow Energy Index)。 ### MILP模型目标函数与约束示例(数学形式): #### 目标函数(最小化能量消耗): $$ \min \sum_{i=1}^{7} w_i \cdot T_i $$ 其中: - $ T_i $:第i个加热区的设定温度 - $ w_i $:权重系数(由BPNN预测结果得到) #### 约束条件: 1. $ T_{i}^{min} \leq T_i \leq T_{i}^{max} $ (温度上下限) 2. $ T_i \in \mathbb{Z} $ (整数温度) ### Python实现(使用PuLP库): ```python from pulp import LpMinimize, LpProblem, LpVariable, lpSum, LpStatus # 创建MILP问题 prob = LpProblem("Reflow_Recipe_Optimization", LpMinimize) # 定义变量:每个加热区的温度 T = [LpVariable(f"T{i}", lowBound=lower[i], upBound=upper[i], cat="Integer") for i in range(7)] # 设置目标函数(假设w为权重) w = [1.2, 1.1, 1.0, 0.95, 0.9, 0.85, 0.8] # 权重 prob += lpSum(w[i] * T[i] for i in range(7)) # 添加其他约束(如相邻区温度差限制等) for i in range(6): prob += T[i+1] - T[i] <= 10 # 温度变化不能太大 # 求解 prob.solve() # 输出结果 print("Status:", LpStatus[prob.status]) for i in range(7): print(f"T{i+1} = {T[i].value()}") ``` --- ## 三、关键贡献总结 1. **阶段式数据分割**:将热曲线分为ramp、soak、reflow三个阶段,提高模型预测精度。 2. **BPNN预测模型**:快速预测各加热区温度设置,为MILP提供初始上下限。 3. **MILP优化模型**:结合预测结果,最小化能耗,生成最优回流焊配方。 4. **非接触式预测**:通过热电偶数据训练模型,减少实验次数,提高效率。 --- ##
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