Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

Structural Aspects and Prediction of Calmodulin-Binding Proteins

Calmodulin (CaM) is an important intracellular protein that binds Ca²⁺ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca²⁺ concentration through interactions with CaM.     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

Prediction of Flooding in Packed Liquid-Liquid and High-Pressure Extraction Columns Using a Gaussian Process

Reliable prediction of flooding conditions is needed for sizing and operating packed extraction columns. Due to the complex interplay of physicochemical properties, operational parameters and the packing-specific properties, it is challenging to develop accurate semi-empirical or rigorous models with a high validity range. State of the art models may therefore fail to predict flooding accurately. To overcome this problem, a data-driven model based on Gaussian processes is developed to predict flooding for packed liquid-liquid and high-pressure extraction columns. The optimized Gaussian process for the liquid-liquid extraction column results in an average absolute relative error (AARE) of 15.23 %, whereas the algorithm for the high-pressure extraction column results in an AARE of 13.68 %. Both algorithms can predict flooding curves for different packing geometries and chemical systems precisely.     

Farmers' preferences for adopting on-farm concentration of raw milk: Results from a discrete choice experiment in Germany

Milk concentrates are used in the manufacturing of dairy products such as yogurt and cheese or are processed into milk powder. Processes for the nonthermal separation of water and valuable milk ingredients are becoming increasingly widespread at farm level. The technical barriers to using farm-manufactured milk concentrate in dairies are minimal, hence the suspicion that the practice of on-farm raw milk concentration is still fairly uncommon for economic reasons. This study, therefore, set out to investigate farmers' potential willingness to adopt a raw milk concentration plant. The empirical analysis was based on discrete choice experiments with 75 German dairy farmers to identify preferences and the possible adoption of on-farm raw milk concentration. The results showed that, in particular, farmers who deemed the current milk price to be insufficient viewed on-farm concentration using membrane technology as an option for diversifying their milk sales. We found no indication that adoption would be impeded by a lack of trustworthy information on milk processing technologies or capital.     

Adaptive GLR-, Rao- and Wald-based CFAR detectors for a subspace signal embedded in structured Gaussian interference

The problem of detecting a subspace signal embedded in subspace Gaussian interference and thermal noise is studied in this paper. In this problem, both the signal-independent and signal-dependent interferences are assumed to be present, therefore the overall interference subspace covers the signal subspace. The approach of this paper extends previous works involving either of those two kinds of interferences. A set of secondary data containing only interference plus noise is employed to estimate the interference covariance matrix and the noise power. Three new detectors are designed via the generalized likelihood ratio (GLR), Rao and Wald tests, respectively. Their probabilities of false alarms (PFAs) and detections are analytically derived. The PFAs show that the new detectors have the constant false alarm rate (CFAR) property against the interference and noise. Numerical results show that the new detectors outperform their counterparts for the studied problem. Furthermore, the new detectors are less sensitive to the secondary data size and to the mismatched subspace signal than some other detectors, such as the GLR detector (GLRD), the adaptive matched filter (AMF), the adaptive subspace detector (ASD), etc.     

Output-relevant Variational autoencoder for Just-in-time soft sensor modeling with missing data

Main challenges for developing data-based models lie in the existence of high-dimensional and possibly missing observations that exist in stored data from industry process. Variational autoencoder (VAE) as one of the deep learning methods has been applied for extracting useful information or features from high-dimensional dataset. Considering that existing VAE is unsupervised, an output-relevant VAE is proposed for extracting output-relevant features in this work. By using correlation between process variables, different weight is correspondingly assigned to each input variable. With symmetric Kullback–Leibler (SKL) divergence, the similarity is evaluated between the stored samples and a query sample. According to the values of the SKL divergence, data relevant for modeling are selected. Subsequently, Gaussian process regression (GPR) is utilized to establish a model between the input and the corresponding output at the query sample. In addition, owing to the common existence of missing data in output data set, the parameters and missing data in the GPR are estimated simultaneously. A practical debutanizer industrial process is utilized to illustrate the effectiveness of the proposed method.     

TCBR-HMM: An HMM-based text classifier with a CBR system

This paper presents an innovative solution to model distributed adaptive systems in biomedical environments. We present an original TCBR-HMM (Text Case Based Reasoning-Hidden Markov Model) for biomedical text classification based on document content. The main goal is to propose a more effective classifier than current methods in this environment where the model needs to be adapted to new documents in an iterative learning frame. To demonstrate its achievement, we include a set of experiments, which have been performed on OSHUMED corpus. Our classifier is compared with Naive Bayes and SVM techniques, commonly used in text classification tasks. The results suggest that the TCBR-HMM Model is indeed more suitable for document classification. The model is empirically and statistically comparable to the SVM classifier and outperforms it in terms of time efficiency.     

基于随机光栅的可调谐随机光纤激光器

提出一种基于随机光栅与高反射布拉格光栅(FBG)相结合的可调谐随机光纤激光器。利用980nm泵浦光源泵浦一段7m长的掺铒光纤(EDF)进行增益放大,由随机光栅提供随机反馈。随机光栅长7cm,具有约10000个折射率修改点,这些点由飞秒激光逐点写入,并沿光纤方向随机分布,两点相邻间隔小于10μm。同时,利用中心波长为1548nm的高反射FBG来组成半开放腔结构,实现了随机激光的输出。实验测得的泵浦阈值功率仅为18mW,斜率效率高达13.2%,并通过改变FBG的中心波长,实现了输出激光波长的可调谐,调谐范围为4.45nm(1548.04~1552.49nm)。得益于半开放式激光腔的设计和EDF的高增益,整个系统具有阈值低、效率高、结构简单等优点。