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This study proposes a novel hybrid computational approach that integrates the artificial dragonfly algorithm (ADA) with the Hopfield neural network (HNN) to achieve an optimal representation of the Exact Boolean kSatisfiability (EBkSAT) logical rule. The primary objective is to investigate the effectiveness and robustness of the ADA algorithm in expediting the training phase of the HNN to attain an optimized EBkSAT logic representation. To assess the performance of the proposed hybrid computational model, a specific Exact Boolean kSatisfiability problem is constructed, and simulated data sets are generated. The evaluation metrics employed include the global minimum ratio (GmR), root mean square error (RMSE), mean absolute percentage error (MAPE), and network computational time (CT) for EBkSAT representation. Comparative analyses are conducted between the results obtained from the proposed model and existing models in the literature. The findings demonstrate that the proposed hybrid model, ADA-HNN-EBkSAT, surpasses existing models in terms of accuracy and computational time. This suggests that the ADA algorithm exhibits effective compatibility with the HNN for achieving an optimal representation of the EBkSAT logical rule. These outcomes carry significant implications for addressing intricate optimization problems across diverse domains, including computer science, engineering, and business., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Various techniques for dorsal hand vein (DHV) pattern extraction have been introduced using small datasets with poor and inconsistent segmentation. This work compared manual segmentation with our proposed hybrid automatic segmentation method (HHM) for this classification problem., Methods: Manual segmentation involved selecting a region-of-interest (ROI) in images from the Bosphorus dataset to generate ground truth data. The HHM combined histogram equalization and morphological and thresholding-based algorithms to localize veins from hand images. The data were divided into training, validation, and testing sets with an 8:1:1 ratio before training AlexNet. We considered three image augmentation strategies to enlarge our training sets. The best training hyperparameters were found using the manually segmented dataset., Results: We obtained a good test accuracy (91.5%) using the model trained with manually segmented images. The HHM method showed slightly inferior performance (76.5%). Considerable improvement was observed in the test accuracy of the model trained with the inclusion of automatically segmented and augmented images (84%), with low false acceptance and false rejection rates (0.00035% and 0.095%, respectively). A comparison with past studies further demonstrated the competitiveness of our technique., Conclusions: Our technique can be feasible for extracting the ROI in DHV images. This strategy provides higher consistency and greater efficiency than the manual approach.

Fiber optical parametric amplifiers (FOPAs) operating based on four-wave mixing (FWM) are versatile devices with increasing applications in optical communication systems. In this paper, the effects of dispersion fluctuations on the performance of bandwidth, ripple, parametric gain, and saturation power of a two-pump FOPA based on four-wave and six-wave models are studied and compared. Coupled-amplitude equations representing the non-degenerate FWM process in optical fiber are solved numerically to compute the parametric gain over the communication wavelengths. The behaviors of the performance parameters are critically analyzed and compared with different types of fluctuation strengths (or amplitudes) specified by the combinations of correlation length ( L c ) and fluctuation amplitude ( σ ). Based on the results, it was found that the flat gain bandwidth for the four-wave model remains unchanged and is insensitive to the strengths of fluctuations. The gain ripples, however, get higher as the fluctuation strengths increase. On the other hand, the flat gain bandwidths of the six-wave model are hardly identified due to the tremendous and continuous ripples within the pump wavelengths. In addition, the minimum parametric gain values for both four-wave and six-wave models reduce as the fluctuation strengths increase. Also, the lowest value of parametric gain leads to the highest saturation power and vice versa. The dispersion fluctuations affect the FWM process's efficiency and deteriorate the overall amplifier performance, particularly for the six-wave model. The numerical analysis obtained via the six-wave model is especially useful since this model closely matches with practical circumstances.

Objectives: Different complex strategies of fusing handcrafted descriptors and features from convolutional neural network (CNN) models have been studied, mainly for two-class Papanicolaou (Pap) smear image classification. This paper explores a simplified system using combined binary coding for a five-class version of this problem., Methods: This system extracted features from transfer learning of AlexNet, VGG19, and ResNet50 networks before reducing this problem into multiple binary sub-problems using error-correcting coding. The learners were trained using the support vector machine (SVM) method. The outputs of these classifiers were combined and compared to the true class codes for the final prediction., Results: Despite the superior performance of VGG19-SVM, with mean ± standard deviation accuracy and sensitivity of 80.68% ± 2.00% and 80.86% ± 0.45%, respectively, this model required a long training time. There were also false-negative cases using both the VGGNet-SVM and ResNet-SVM models. AlexNet-SVM was more efficient in terms of running speed and prediction consistency. Our findings also showed good diagnostic ability, with an area under the curve of approximately 0.95. Further investigation also showed good agreement between our research outcomes and that of the state-of-the-art methods, with specificity ranging from 93% to 100%., Conclusions: We believe that the AlexNet-SVM model can be conveniently applied for clinical use. Further research could include the implementation of an optimization algorithm for hyperparameter tuning, as well as an appropriate selection of experimental design to improve the efficiency of Pap smear image classification.

The impact of random dispersion fluctuations on the gain and saturation behavior of a one-pump fiber optical parametric amplifier (1-P FOPA) in the presence of fourth-order dispersion coefficient (β 4 ) is investigated. Three coupled amplitude equations with fiber losses are solved numerically for the calculation of the pump, signal, and idler. The performances of 1-P FOPA are also analyzed with variation of dispersion fluctuation amplitude (σ) and correlation length (L c ). Based on the numerical results, it is found that the gain spectra and saturation curves exhibit some differences when β 4 is considered. In comparison with the case where β 4 is ignored, the peak gain remains the same, but the 3 dB bandwidth increases when β 4 exists. Another notable difference is that the saturation power is shifted to lower or higher values, depending on the σ and L c parameters. In general, the peak gain reduces as σ increases, and the peak gain reduction is greater for the case of shorter L c . The numerical analysis is probably useful, especially for the case where the signal wavelength is detuned far from the pump wavelength.

Recent studies have shown that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and preferentially induces apoptosis in cancer cells, including acute myeloid leukemia (AML). However, the underlying molecular mechanisms are not well understood. The present study demonstrates that DZNep induces robust apoptosis in AML cell lines, primary cells, and targets CD34(+)CD38(-) leukemia stem cell (LSC)-enriched subpopulations. Using RNA interference (RNAi), gene expression profiling, and ChIP, we identified that TXNIP, a major redox control molecule, plays a crucial role in DZNep-induced apoptosis. We show that disruption of PRC2, either by DZNep treatment or EZH2 knockdown, reactivates TXNIP, inhibits thioredoxin activity, and increases reactive oxygen species (ROS), leading to apoptosis. Furthermore, we show that TXNIP is down-regulated in AML and is a direct target of PRC2-mediated gene silencing. Consistent with the ROS accumulation on DZNep treatment, we also see a signature of endoplasmic reticulum (ER) stress-regulated genes, commonly associated with cell survival, down-regulated by DZNep. Taken together, we uncover a novel molecular mechanism of DZNep-mediated apoptosis and propose that EZH2 may be a potential new target for epigenetic treatment in AML.

Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation.

Purpose of Work: mutation of the p53 gene is the most common genetic alteration in human cancers. Our study proposes to rationally design a p53 antisense oligonucleotide (ASO) repository, which contains a series of ASOs containing single nucleotide differences to discriminate between each mutant and wild type (WT) p53. The Sfold software was used to predict target-accessibility and we designed an initial series of antisense oligonucleotides (ASO) that target the p53 mutants A161T, R175H and R249S. Western-blot analysis indicated that ASOs strongly inhibited the expression of p53 mutants in a panel of human tumor cell lines (SNU-449, SK-BR-3 and PLC/PRF/5) while having little effect on the expression of WT p53 (HepG2 cells). In three cancer lines harboring each of the p53 mutations, mutant-specific ASO treatment led to a dose-dependent inhibition of cell growth, cell viability, colony formation and invasion, and expression of mutant p53-dependent survival proteins. Our preliminary results indicate that a single nucleotide difference in ASOs can discriminate between mutant and WT p53. These observations support the hypothesis that a p53 ASO repository can be a potentially valuable tool to knock down oncogenic mutant p53 and warrant the testing of a p53 ASO repository in in vivo settings.

In up to one-third of patients with acute myeloid leukemia, a C-terminal frame-shift mutation results in abnormal and abundant cytoplasmic accumulation of the usually nucleoli-bound protein nucleophosmin (NPM), and this is thought to function in cancer pathogenesis. Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8-mediated myeloid differentiation. Our data hence provide a potential explanation for the myeloid-specific involvement of cytoplasmic NPM in the leukemogenesis of a large subset of acute myeloid leukemia.

To further investigate potential mechanisms of resistance to FLT3 inhibitors, we developed a resistant cell line by long-term culture of MV4-11 cells with ABT-869, designated as MV4-11-R. Gene profiling reveals up-regulation of FLT3LG (FLT3 ligand) and BIRC5 (survivin), but down-regulation of SOCS1, SOCS2, and SOCS3 in MV4-11-R cells. Hypermethylation of these SOCS genes leads to their transcriptional silencing. Survivin is directly regulated by STAT3. Stimulation of the parental MV4-11 cells with FLT3 ligand increases the expression of survivin and phosphorylated protein STAT1, STAT3, STAT5. Targeting survivin by short-hairpin RNA (shRNA) in MV4-11-R cells induces apoptosis and augments ABT-869-mediated cytotoxicity. Overexpression of survivin protects MV4-11 from apoptosis. Subtoxic dose of indirubin derivative (IDR) E804 resensitizes MV4-11-R to ABT-869 treatment by inhibiting STAT signaling activity and abolishing survivin expression. Combining IDR E804 with ABT-869 shows potent in vivo efficacy in the MV4-11-R xenograft model. Taken together, these results demonstrate that enhanced activation of STAT pathways and overexpression of survivin are important mechanisms of resistance to ABT-869, suggesting that the STAT pathways and survivin could be potential targets for reducing resistance developed in patients receiving FLT3 inhibitors.

The objective of this study was to evaluate the effect of implanting an Antigen Release Devices (ARD) into dairy cows during the lactation cycle to induce an immune response. Subsequently, the concentrations of lactoferrin in serum and milk were measured. Forty healthy adult Chinese Holstein cows were divided into two equal groups: a test group and a control group. Animals in the test group received ARD implants, whereas the control group animals were not treated. An even spread across the two groups was maintained with animal selection based on parity, the lactation days and milk yields. The concentrations of lactoferrin in the serum and milk of all forty animals were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). The results show that the implantation of an ARD did not significantly increase the concentration of lactoferrin in the serum and milk throughout the whole experiment period except on two occasions. The levels of lactoferrin in the milk and serum significantly increased on day 7 and on day 11 after implantation (p<0.05). There was a strong correlation between milk lactoferrin and serum lactoferrin (r=0.564, P<0.01). Three separate ARDs were used releasing its antigen load on day 0, 14 and 28 to induce a primary, secondary and tertiary response respectively. As the significant increases in the lactoferrin levels were only observed after the first ARD release, the effects of lactoferrin appears to be associated with the early phase of the immune response, consistent with its role in the host's innate defense system.

Feed spacers in spiral-wound reverse osmosis membrane modules are highly susceptible to deposition or attachment of suspended particulates and organic matters in the feed stream. This type of fouling can cause a significant pressure drop along the membrane channel (differential pressure) without much effect on the average permeate flux. In practical applications, membrane cleaning is often triggered when the differential pressure in a membrane channel exceeds a threshold value. A mathematical model was developed to simulate the development of differential pressure in the feed channel resulting from foulant capture by the feed spacers. Simulations were carried out to investigate and demonstrate the effect of various parameters on differential pressures in the membrane channel. Differential pressures observed in a two-stage reverse osmosis water reclamation plant were simulated with the model, and the results showed that the model could adequately describe the increase of differential pressure with operating time in the reverse osmosis plant.