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Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions.

Software-Defined Networking (SDN) offers a centralized network management approach that can effectively address the complex and varied traffic demands characteristic of Industrial Internet of Things (IIoT) environments by decoupling the control plane from the data plane. The centralized control architecture of SDN necessitates the performance optimization of controllers to manage diverse traffic efficiently within IIoT applications. This paper explores the criteria for selecting controllers in SDN-enabled IIoT (SD-IIoT) environments, utilizing the Less Complex Analytic Network Process (LC-ANP) to establish their prioritization. A ranking system for SD-IIoT controllers is formulated using LC-ANP, and experimental validation of this method underscores its effectiveness in optimizing controller performance. The proposed approach enhances the overall efficiency of SDN-enabled IIoT networks, as evidenced by experimental evaluations measuring delay, throughput, packet loss ratio (PLR), and jitter across five different topologies with varying nodes and edges. The experiments indicate an overall increase in the average throughput, and a decrease in delay, jitter, and PLR. The results also show that the suggested strategy and proposed controller surpass the benchmark controller in complex network topologies. These results confirm the method’s capacity to significantly improve network performance in SD-IIoT applications.

The multi-input multioutput (MIMO) systems involving multirelational signals generated from distributed sources have been emerging as the most generalized model in practice. The existing work for characterizing such a MIMO system is to build a corresponding transform tensor, each of whose entries turns out to be the individual z-transform of a discrete-time impulse response sequence. However, when a MIMO system has a global feedback mechanism, which also involves multirelational signals, the aforementioned individual z-transforms of the overall transfer tensor are quite difficult to formulate. Therefore, a new mathematical framework to govern both feedforward and feedback MIMO systems is in crucial demand. In this work, we define the tensor z-transform to characterize a MIMO system involving multirelational signals as a whole rather than the individual entries separately, which is a novel concept for system analysis. To do so, we extend Cauchy’s integral formula and Cauchy’s residue theorem from scalars to arbitrary-dimensional tensors, and then, to apply these new mathematical tools, we establish to undertake the inverse tensor z-transform and approximate the corresponding discrete-time tensor sequences. Our proposed new tensor z-transform in this work can be applied to design digital tensor filters including infinite-impulse-response (IIR) tensor filters (involving global feedback mechanisms) and finite-impulse-response (FIR) tensor filters. Finally, numerical evaluations are presented to demonstrate certain interesting phenomena of the new tensor z-transform.

Abstract Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to drug treatment. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic. Emphasizing on the system-level complexity of cancer, we devised a procedure to integrate multiple heterogeneous data, including biological networks, genomics, inhibitor profiling, and gene-disease associations, into a unified graph structure. In order to construct compact, yet information-rich cancer-specific networks, we developed a novel graph reduction algorithm. Driven by not only the topological information, but also the biological knowledge, the graph reduction increases the feature-only entropy while preserving the valuable graph-feature information. Subsequent comparative benchmarking simulations employing a tissue level cross-validation protocol demonstrate that the accuracy of a graph-based predictor of the drug efficacy is 0.68, which is notably higher than those measured for more traditional, matrix-based techniques on the same data. Overall, the non-Euclidean representation of the cancer-specific data improves the performance of machine learning to predict the response of cancer to pharmacotherapy. The generated data are freely available to the academic community at https://osf.io/dzx7b/ .

This study explores and analyzes students’ difficulties in learning an ERP system to help design more appropriate teaching methods and materials. Global enterprises have widely used ERP systems to manage their operations effectively and efficiently. Hence, many business schools have offered courses on ERP systems to sharpen ERP skills for their students. To help design more appropriate teaching methods and materials for ERP learning, one must know students’ difficulties in understanding. This study analyzes students’ difficulties in learning the Oracle E-Business Suite ERP system through interviews and qualitative analysis. As a result, this study identifies five categories of problems in the various areas of the Revised Bloom’s Taxonomy. Their relevant educational objectives can guide the redesign of ERP teaching methods and materials. One of the difficulties belongs to the area of Remember Factual Knowledge. The rest of them are in Understand, Remember, Apply, and Analysis of Procedural Knowledge. Lastly, this study provides some implications for teaching ERP.

Abstract Traditional techniqueset identification, we developed GraphDTI, a robust machine learning framework integrating the molecular-level information on drugs, proteins, and binding sites with the system-level information on gene expression and protein-protein interactions. In order to properly evaluate the performance of GraphDTI, we compiled a high-quality benchmarking dataset and devised a new cluster-based cross-validation p to identify macromolecular targets for drugs utilize solely the information on a query drug and a putative target. Nonetheless, the mechanisms of action of many drugs depend not only on their binding affinity toward a single protein, but also on the signal transduction through cascades of molecular interactions leading to certain phenotypes. Although using protein-protein interaction networks and drug-perturbed gene expression profiles can facilitate system-level investigations of drug-target interactions, utilizing such large and heterogeneous data poses notable challenges. To improve the state-of-the-art in drug targrotocol. Encouragingly, GraphDTI not only yields an AUC of 0.996 against the validation dataset, but it also generalizes well to unseen data with an AUC of 0.939, significantly outperforming other predictors. Finally, selected examples of identified drug-target interactions are validated against the biomedical literature. Numerous applications of GraphDTI include the investigation of drug polypharmacological effects, side effects through off-target binding, and repositioning opportunities.

Unmanned aerial vehicles (UAVs) employed as airborne base stations (BSs) are considered the essential components in future sixth-generation wireless networks due to their mobility and line-of-sight communication links. For a UAV-assisted ad hoc network, its total channel capacity is greatly influenced by the deployment of UAV-BSs and the corresponding coverage layouts, where square and hexagonal cells are partitioned to divide the zones individual UAVs should serve. In this paper, the total channel capacities of these two kinds of coverage layouts are evaluated using our proposed novel computationally efficient channel capacity estimation scheme. The mean distance (MD) between a UAV-BS in the network and its served users as well as the MD from these users to the neighboring UAV-BSs are incorporated into the estimation of the achievable total channel capacity. We can significantly reduce the computational complexity by using a new polygon division strategy. The simulation results demonstrate that the square cell coverage layout can always lead to a superior channel capacity (with an average increase of 7.67% to be precise) to the hexagonal cell coverage layout for UAV-assisted ad hoc networks.

Abstract Background The efficiency of drug development defined as a number of successfully launched new pharmaceuticals normalized by financial investments has significantly declined. Nonetheless, recent advances in high-throughput experimental techniques and computational modeling promise reductions in the costs and development times required to bring new drugs to market. The prediction of toxicity of drug candidates is one of the important components of modern drug discovery. Results In this work, we describe eToxPred, a new approach to reliably estimate the toxicity and synthetic accessibility of small organic compounds. eToxPred employs machine learning algorithms trained on molecular fingerprints to evaluate drug candidates. The performance is assessed against multiple datasets containing known drugs, potentially hazardous chemicals, natural products, and synthetic bioactive compounds. Encouragingly, eToxPred predicts the synthetic accessibility with the mean square error of only 4% and the toxicity with the accuracy of as high as 72%. Conclusions eToxPred can be incorporated into protocols to construct custom libraries for virtual screening in order to filter out those drug candidates that are potentially toxic or would be difficult to synthesize. It is freely available as a stand-alone software at https://github.com/pulimeng/etoxpred.

In order to perform big-data analytics, regression involving large matrices is often necessary. In particular, large scale regression problems are encountered when one wishes to extract semantic patterns for knowledge discovery and data mining. When a large matrix can be processed in its factorized form, advantages arise in terms of computation, implementation, and data-compression. In this work, we propose two new parallel iterative algorithms as extensions of the Gauss–Seidel algorithm (GSA) to solve regression problems involving many variables. The convergence study in terms of error-bounds of the proposed iterative algorithms is also performed, and the required computation resources, namely time- and memory-complexities, are evaluated to benchmark the efficiency of the proposed new algorithms. Finally, the numerical results from both Monte Carlo simulations and real-world datasets are presented to demonstrate the striking effectiveness of our proposed new methods.

Cooperative automatic modulation classification (CAMC) using a swarm of sensors is intriguing nowadays as it would be much more robust than the conventional single-sensing-node automatic modulation classification (AMC) method. We propose a novel robust CAMC approach using vectorized soft decision fusion in this work. In each sensing node, the local Hamming distances between the graph features acquired from the unknown target signal and the training modulation candidate signals are calculated and transmitted to the fusion center (FC). Then, the global CAMC decision is made by the indirect vote which is translated from each sensing node’s Hamming-distance sequence. The simulation results demonstrate that, when the signal-to-noise ratio (SNR) was given by η ≥ 0dB, our proposed new CAMC scheme’s correct classification probability Pcc could reach up close to 100%. On the other hand, our proposed new CAMC scheme could significantly outperform the single-node graph-based AMC technique and the existing decision-level CAMC method in terms of recognition accuracy, especially in the low-SNR regime.

Blind modulation classification (MC) is an integral part of designing an adaptive or intelligent transceiver for future wireless communications. Blind MC has several applications in the adaptive and automated systems of sixth generation (6G) communications to improve spectral efficiency and power efficiency, and reduce latency. It will become a integral part of intelligent software-defined radios (SDR) for future communication. In this paper, we provide various MC techniques for orthogonal frequency division multiplexing (OFDM) signals in a systematic way. We focus on the most widely used statistical and machine learning (ML) models and emphasize their advantages and limitations. The statistical-based blind MC includes likelihood-based (LB), maximum a posteriori (MAP) and feature-based methods (FB). The ML-based automated MC includes k-nearest neighbors (KNN), support vector machine (SVM), decision trees (DTs), convolutional neural networks (CNNs), recurrent neural networks (RNNs), and long short-term memory (LSTM) based MC methods. This survey will help the reader to understand the main characteristics of each technique, their advantages and disadvantages. We have also simulated some primary methods, i.e., statistical- and ML-based algorithms, under various constraints, which allows a fair comparison among different methodologies. The overall system performance in terms bit error rate (BER) in the presence of MC is also provided. We also provide a survey of some practical experiment works carried out through National Instrument hardware over an indoor propagation environment. In the end, open problems and possible directions for blind MC research are briefly discussed.

Comprehensive characterization of ligand-binding sites is invaluable to infer molecular functions of hypothetical proteins, trace evolutionary relationships between proteins, engineer enzymes to achieve a desired substrate specificity, and develop drugs with improved selectivity profiles. These research efforts pose significant challenges owing to the fact that similar pockets are commonly observed across different folds, leading to the high degree of promiscuity of ligand-protein interactions at the system-level. On that account, novel algorithms to accurately classify binding sites are needed. Deep learning is attracting a significant attention due to its successful applications in a wide range of disciplines. In this communication, we present DeepDrug3D, a new approach to characterize and classify binding pockets in proteins with deep learning. It employs a state-of-the-art convolutional neural network in which biomolecular structures are represented as voxels assigned interaction energy-based attributes. The current implementation of DeepDrug3D, trained to detect and classify nucleotide- and heme-binding sites, not only achieves a high accuracy of 95%, but also has the ability to generalize to unseen data as demonstrated for steroid-binding proteins and peptidase enzymes. Interestingly, the analysis of strongly discriminative regions of binding pockets reveals that this high classification accuracy arises from learning the patterns of specific molecular interactions, such as hydrogen bonds, aromatic and hydrophobic contacts. DeepDrug3D is available as an open-source program at https://github.com/pulimeng/DeepDrug3D with the accompanying TOUGH-C1 benchmarking dataset accessible from https://osf.io/enz69/.

We consider the use of multiple mobile agents to explore an unknown area. The area is orthogonal, such that all perimeter lines run both vertically and horizontally. The area may consist of unknown rectangular holes which are non-traversable internally. For the sake of analysis, we assume that the area is discretized into N points allowing the agents to move from one point to an adjacent one. Mobile agents communicate through face-to-face communication when in adjacent points. The objective of exploration is to develop an online algorithm that will explore the entire area while reducing the total work of all k agents, where the work is measured as the number of points traversed. We propose splitting the exploration into two alternating tasks, perimeter and room exploration. The agents all begin with the perimeter scan and when a room is found they transition to room scan after which they continue with perimeter scan until the next room is found and so on. Given the total traversable points N, our algorithm completes in total O ( N ) work with each agent performing O ( N / k ) work, namely the work is balanced. If the rooms are hole-free the exploration time is also asymptotically optimal, O ( N / k ) . To our knowledge, this is the first agent coordination algorithm that considers simultaneously work balancing and small exploration time.

Least-square estimation (LSE) and multiple-parameter linear regression (MLR) are the important estimation techniques for engineering and science, especially in the mobile communications and signal processing applications. The majority of computational complexity incurred in LSE and MLR arises from a Hermitian matrix inversion. In practice, the Yule-Walker equations are not valid, and hence the Levinson-Durbin algorithm cannot be employed for general LSE and MLR problems. Therefore, the most efficient Hermitian matrix inversion method is based on the Cholesky factorization. In this paper, we derive a new dyadic recursion algorithm for sequential rank-adaptive Hermitian matrix inversions. In addition, we provide the theoretical computational complexity analyses to compare our new dyadic recursion scheme and the conventional Cholesky factorization. We can design a variable model-order LSE (MLR) using this proposed dyadic recursion approach thereupon. Through our complexity analyses and the Monte Carlo simulations, we show that our new dyadic recursion algorithm is more efficient than the conventional Cholesky factorization for the sequential rank-adaptive LSE (MLR) and the associated variable model-order LSE (MLR) can seek the trade-off between the targeted estimation performance and the required computational complexity. Our proposed new scheme can benefit future portable and mobile signal processing or communications devices.

BackgroundThrombospondin type I domain containing 7A (THSD7A) is a novel neural protein that is known to affect endothelial migration and vascular patterning during development. To further understand the role of THSD7A in angiogenesis, we investigated the post-translational modification scheme of THS7DA and to reveal the underlying mechanisms by which this protein regulates blood vessel growth.Methodology/principal findingsFull-length THSD7A was overexpressed in human embryonic kidney 293T (HEK293T) cells and was found to be membrane associated and N-glycosylated. The soluble form of THSD7A, which is released into the cultured medium, was harvested for further angiogenic assays. We found that soluble THSD7A promotes human umbilical vein endothelial cell (HUVEC) migration and tube formation. HUVEC sprouts and zebrafish subintestinal vessel (SIV) angiogenic assays further revealed that soluble THSD7A increases the number of branching points of new vessels. Interestingly, we found that soluble THSD7A increased the formation of filopodia in HUVEC. The distribution patterns of vinculin and phosphorylated focal adhesion kinase (FAK) were also affected, which implies a role for THSD7A in focal adhesion assembly. Moreover, soluble THSD7A increased FAK phosphorylation in HUVEC, suggesting that THSD7A is involved in regulating cytoskeleton reorganization.Conclusions/significanceTaken together, our results indicate that THSD7A is a membrane-associated N-glycoprotein with a soluble form. Soluble THSD7A promotes endothelial cell migration during angiogenesis via a FAK-dependent mechanism and thus may be a novel neuroangiogenic factor.

The voice activity detection (VAD) is crucial in all kinds of speech applications. However, almost all existing VAD algorithms suffer from the nonstationarity of both speech and noise. To combat this difficulty, we propose a new voice activity detector, which is based on the Mel-energy features and an adaptive threshold related to the signal-to-noise ratio (SNR) estimates. In this paper, we first justify the robustness of the Bayes classifier using the Mel-energy features over that using the Fourier spectral features in various noise environments. Then, we design an algorithm using the dynamic Mel-energy estimator and the adaptive threshold, which depends on the SNR estimates. In addition, a realignment scheme is incorporated to correct the sparse-and-spurious noise estimates. Numerous simulations are carried out to evaluate the performance of our proposed VAD method and the comparisons are made with a couple of existing representative schemes, namely, the VAD using the likelihood ratio test with Fourier spectral energy features and that based on the enhanced time-frequency parameters. Three types of noises, namely, white noise (stationary), babble noise (nonstationary), and vehicular noise (nonstationary) were artificially added by the computer for our experiments. As a result, our proposed VAD algorithm significantly outperforms other existing methods as illustrated by the corresponding receiver operating characteristics (ROC) curves. Finally, we demonstrate one of the major applications, namely, speech waveform compression associated with our new robust VAD scheme and quantify the effectiveness in terms of compression efficiency.

A general mathematical model is provided for the ultrasonic signals collected by the pulse-echo sensors and a totally blind novel signal processing nondestructive testing (NDT) technique is designed relying neither on priori signal information nor any manual effort. The detected ridge information is used to estimate the transmission and attenuation coefficients associated with any arbitrary materials sample for the fabrication quality control.

Power-line communications (PLCs) endure a severe transmission channel distortion due to Gaussian noise, impulsive noise, and multipath self-interference. Conventional transmission models with white Gaussian noise would be very inappropriate and impair the necessary channel estimation drastically to the PLC receivers. In this study, a statistical model for impulsive noise, namely Middleton Class A model, is employed for Gaussian information sources. Robust channel estimation algorithms based on a novel parameter estimation scheme are established thereby. Superior to the conventional robust-leastsquare estimation algorithms, the authors' proposed new adaptive robust-least-square estimation methods can take advantage of the statistical parameter estimation for impulsive noise. The studies on the theoretical and practical aspects of their proposed new parameter estimator are also presented. [ABSTRACT FROM AUTHOR]

In this study, the authors tackle the problem of carrier aggregation (CA) in downlink of long-term evolution advanced (LTE-A) femtocell networks. They propose a novel approach in a new perspective: namely, user navigation, to improve the CA performance of an LTE-A system in the indoor environment. The proposed indoor user navigation (IUN) algorithm exploits the a priori knowledge of radio interferences between femtocells to build a geometric qualityof- service (QoS) map, which can be utilised to navigate users toward the locations suitable for performing CA to satisfy the QoS requirements. The simulations demonstrate the effectiveness of the proposed IUN algorithm to improve the CA performance in terms of the aggregate throughput for the LTE-A femtocell networks. [ABSTRACT FROM AUTHOR]

In this letter, we propose new frequency-domain pilot-multiplexing techniques (FDPMTs) for the channel estimation and equalization in orthogonal frequency-division multiplexing (OFDM) systems. A robust and effective pilot insertion and detection scheme is devised thereby. These pilot positions are optimally selected to minimize the distortion of the transmitted time-domain signal caused by the subcarrier-removal at the corresponding pilot positions. Besides, three different blind pilot-detection techniques are designed at the receiver without any a priori knowledge of the pilot positions, and the distorted data symbols can thus be iteratively reconstructed. Rigorous theoretical analysis and Monte Carlo simulation results both demonstrate that our proposed new OFDM system using dynamical pilot positions is more robust than the conventional OFDM system using the fixed pilot positions over multipath fading channels. [ABSTRACT FROM AUTHOR]