Search Results (22)

When training a neural network, the choice of activation function can greatly impact its performance. A function with a larger derivative may cause the coefficients of the latter layers to deviate further from the calculated direction, making deep learning more difficult to train. However, an activation function with a derivative amplitude of less than one can result in the problem of a vanishing gradient. To overcome this drawback, we propose the application of pseudo-normalization to enlarge some gradients by dividing them by the root mean square. This amplification is performed every few layers to ensure that the amplitudes are larger than one, thus avoiding the condition of vanishing gradient and preventing gradient explosion. We successfully applied this approach to several deep learning networks with hyperbolic tangent activation for image classifications. To gain a deeper understanding of the algorithm, we employed interpretability techniques to examine the network’s prediction outcomes. We discovered that, in contrast to popular networks that learn picture characteristics, the networks primarily employ the contour information of images for categorization. This suggests that our technique can be utilized in addition to other widely used algorithms. Full article

Stilbenes are a group of polyphenols that are gaining steady attention and have promising biological activity. While much attention is given to polyhydroxy compounds derived from resveratrol, other substituents remain largely unexplored. In this work, we present the results of studies on the synthesis, physicochemical characterisation, and ADME parameters simulation of polymethoxy and brominated stilbenes. We also examined their anticancer activity and found that some of the brominated compounds reveal desirable properties. While the brominated derivatives are not significantly more active than the polymethoxy derivatives, they were found to be safer for the tested pseudo-normal cell lines. Full article

Background: Cancer remains a leading cause of morbidity and mortality worldwide, and current therapies are limited by toxicity, cost, and resistance. Inhibition of the MDM2–p53 interaction is a promising anticancer strategy, as this pathway is frequently dysregulated across tumors. Spiro-isatin-thiazolidinone derivatives have shown diverse biological activities, including anticancer effects, but require optimization to improve potency and selectivity. The aims were to design, synthesize, and evaluate novel spiro-isatin-thiazolidinone hybrids with enhanced cytotoxicity against cancer cells and reduced toxicity toward normal cells. Methods: Derivatives were designed using molecular docking against MDM2, followed by structural optimization. Cytotoxic activity was evaluated in vitro by MTT assays on human and murine cancer cell lines and pseudo-normal cells. Docking and 100 ns molecular dynamics simulations assessed binding stability, while ADMET properties were predicted in silico. Results: Several derivatives exhibited micromolar cytotoxicity, with compound 18 emerging as the most potent and selective candidate (IC₅₀ 6.67–8.37 µM across most cancer lines; >100 µM in HaCaT). Docking showed a strong affinity for MDM2 (−10.16 kcal/mol), comparable to the reference ligand, and stable interactions in simulations. ADMET predictions confirmed good oral bioavailability and moderate acute toxicity, fully compliant with Lipinski’s Rule of Five. Overall, the newly synthesized spiro-isatin-thiazolidinone hybrids, particularly compound 18, demonstrated potent and selective anticancer activity, favorable pharmacokinetic properties and a good toxicity profile. Full article

Jaguars play a crucial role in population control across multiple biomes. They are endangered and protected by in situ and ex situ conservation mechanisms to ensure their conservation. Cardiovascular diseases in wild mammals, including jaguars, often have unclear etiopathogenies, underscoring the need for research into novel hemodynamic parameters. This study evaluates the cardiovascular health of fifteen clinically healthy jaguars using conventional and Holter electrocardiography, non-invasive systemic blood pressure measurement, and echocardiography. Chemical restraint was achieved with medetomidine (0.08–0.1 mg/kg) and ketamine (5 mg/kg), with anesthesia reversed using atipamezole (0.25 mg/kg). The average heart rate was 72 ± 18 bpm, with sinus rhythm in ten animals and sinus arrhythmia in five. Six animals exhibited first and second-degree atrioventricular blocks, one had supraventricular complexes, and another had premature ventricular complexes. Non-invasive systolic blood pressure remained stable at 163 ± 29 mmHg during anesthesia. Echocardiographic examination revealed mitral, tricuspid, pulmonary, and aortic valve insufficiencies via color Doppler. The transmitral flow showed a normal E/A ratio and E` < A`, suggesting a pseudonormal ventricular filling pattern. No significant anesthetic complications were observed, affirming the protocol’s safety. This study provides valuable data, validating the anesthetic protocol and establishing reference cardiovascular values for jaguars, thus paving the way for future research in other veterinary species. Full article

It is common knowledge that any topological group that satisfies the lowest separation axiom, $T_0$, is immediately Hausdorff and completely regular; however, this is not the case for normality. This motivates us to introduce the concept of pseudo-normal groups along with pseudo-Tychonoff topological groups as generalizations of the normality and Tychonoffness of topological groups, respectively. We show that every pseudo-normal (resp. pseudo-Tychonoff) topological group is normal (resp. Tychonoff). Generally, the reverse implication of the latter does not hold. Then, we discuss their main properties in detail. To clarify these properties, we provide some examples. Finally, we establish some other results. Full article

Two decades ago, Ngai and Wang introduced a well-known finite type condition (FTC) on the self-similar iterated function system (IFS) with overlaps and used it to calculate the Hausdorff dimension of self-similar sets. In this paper, inspired by Ngai and Wang’s idea, we define a new FTC on self-affine IFS and obtain an analogous formula on the generalized dimensions of self-affine sets. The generalized dimensions raised by He and Lau are used to estimate the Hausdorff dimension of self-affine sets. Full article

The development of new, effective agents for the treatment of breast cancer remains a high-priority task in oncology. A strategy of treatment for this pathology depends significantly on the genotype and phenotype of human breast cancer cells. We aimed to investigate the antitumor activity of new pyrrolidinedione–thiazolidinone hybrid molecules Les-6287, Les-6294, and Les-6328 towards different types of human breast cancer cells of MDA-MB-231, MCF-7, T-47D, and HCC1954 lines and murine breast cancer 4T1 cells by using the MTT, clonogenic and [³H]-Thymidine incorporation assays, flow cytometry, ELISA, and qPCR. The studied hybrids possessed toxicity towards the mentioned tumor cells, with the IC₅₀ ranging from 1.37 to 21.85 µM. Simultaneously, these derivatives showed low toxicity towards the pseudonormal human breast epithelial cells of the MCF-10A line (IC₅₀ > 93.01 µM). Les-6287 at 1 µM fully inhibited the formation of colonies of the MCF-7, MDA-MB-231, and HCC1954 cells, while Les-6294 and Les-6328 did that at 2.5 and 5 µM, respectively. Les-6287 suppressed DNA biosynthesis in the MCF-7, MDA-MB-231, and HCC1954 cells. At the same time, such an effect on the MCF-10A cells was significantly lower. Les-6287 induces apoptosis using extrinsic and intrinsic pathways via a decrease in the mitochondrial membrane potential, increasing the activity of caspases 3/7, 8, 9, and 10 in all immunohistochemically different human breast cancer cells. Les-6287 decreased the concentration of the metastasis- and invasion-related proteins MMP-2, MMP-9, and ICAM-1. It did not induce autophagy in treated cells. In conclusion, the results of our study suggest that the synthesized hybrid pyrrolidinedione–thiazolidinones might be promising agents for treating breast tumors of different types. Full article

Vector normalization is an important process in several algorithms. It is used in classical physical calculations, mathematical techniques, and machine learning, which has witnessed significant advancements in recent years. Normalization and regularization ensure the stability of solutions and play an important role in algorithm convergence. Normalization typically refers to the division of elements by their norm. Division should not be used in algorithmic implementations because its computational cost is considerably higher than that of multiply–add operations. Based on this, there is a well-known method referred to as the fast inverse square root (FISR) algorithm in floating-point calculations (IEEE754). In deeper-level embedded systems that require fast responses or power efficiency, integer instead of real number arithmetic (floating-point number arithmetic) should be used to increase speed. Conversely, in deeper-level embedded systems that require fast responses or power efficiency, integer arithmetic should be used instead of real number arithmetic (floating-point number arithmetic) to increase speed. Therefore, embedded engineers encounter problems in instances in which they use integer arithmetic for implementation, but real number arithmetic is required to compute vectors and other higher-dimensional algebra. There is no conventional normalization algorithm similar to the FISR algorithm for integer arithmetic; however, the proposed pseudo-normalization achieves vector normalization within a restricted domain using only multiply–add operations and bit shifts. This allows for fast and robust operations, even for low-performance MCUs that do not have power-efficient FPUs. As an example, this study demonstrates the computation of the arctangent (Arctan2 function; atan2(y, x)) with high precision using only integer multiply–add operations. In this study, we proposed a method of vector normalization using only integer arithmetic for embedded systems and confirmed its effectiveness by simulation using Verilog. The research results can contribute to various fields such as signal processing of IMU sensor data, faster artificial intelligence training, and efficient rendering of computer graphics. Full article

The steel industry is typical process manufacturing, and the quality and cost of the products can be improved by efficient operation of equipment. This paper proposes an efficient diagnosis and monitoring method for the gearbox, which is a key piece of mechanical equipment in steel manufacturing. In particular, an equipment maintenance plan for stable operation is essential. Therefore, equipment monitoring and diagnosis to prevent unplanned plant shutdowns are important to operate the equipment efficiently and economically. Most plant data collected on-site have no precise information about equipment malfunctions. Therefore, it is difficult to directly apply supervised learning algorithms to diagnose and monitor the equipment with the operational data collected. The purpose of this paper is to propose a pseudo-label method to enable supervised learning for equipment data without labels. Pseudo-normal (PN) and pseudo-abnormal (PA) vibration datasets are defined and labeled to apply classification analysis algorithms to unlabeled equipment data. To find an anomalous state in the equipment based on vibration data, the initial PN vibration dataset is compared with a PA vibration dataset collected over time, and the equipment is monitored for potential failure. Continuous wavelet transform (CWT) is applied to the vibration signals collected to obtain an image dataset, which is then entered into a convolutional neural network (an image classifier) to determine classification accuracy and detect equipment abnormalities. As a result of Steps 1 to 4, abnormal signals have already been detected in the dataset, and alarms and warnings have already been generated. The classification accuracy was over 0.95 at $d=4$, confirming quantitatively that the status of the equipment had changed significantly. In this way, a catastrophic failure can be avoided by performing a detailed equipment inspection in advance. Lastly, a catastrophic failure occurred in Step 9, and the classification accuracy ranged from 0.95 to 1.0. It was possible to prevent secondary equipment damage, such as motors connected to gearboxes, by identifying catastrophic failures promptly. This case study shows that the proposed procedure gives good results in detecting operation abnormalities of key unit equipment. In the conclusion, further promising topics are discussed. Full article

In this paper, we propose robust image-smoothing methods based on ${\mathit{\ell }}_0$ gradient minimization with novel gradient constraints to effectively suppress pseudo-edges. Simultaneously minimizing the ${\mathit{\ell }}_0$ gradient, i.e., the number of nonzero gradients in an image, and the ${\mathit{\ell }}_2$ data fidelity results in a smooth image. However, this optimization often leads to undesirable artifacts, such as pseudo-edges, known as the “staircasing effect”, and halos, which become more visible in image enhancement tasks, like detail enhancement and tone mapping. To address these issues, we introduce two types of gradient constraints: box and ball. These constraints are applied using a reference image (e.g., the input image is used as a reference for image smoothing) to suppress pseudo-edges in homogeneous regions and the blurring effect around strong edges. We also present an ${\mathit{\ell }}_0$ gradient minimization problem based on the box-/ball-type gradient constraints using an alternating direction method of multipliers (ADMM). Experimental results on important applications of ${\mathit{\ell }}_0$ gradient minimization demonstrate the advantages of our proposed methods compared to existing ${\mathit{\ell }}_0$ gradient-based approaches. Full article

Background. This study aimed to investigate the association of preoperative right heart filling indicators with outcomes after coronary artery bypass grafting (CABG) at an 18 month follow up. Methods. Patients who underwent CABG at a single center were included in this study. In addition to the baseline preoperative indicators and perioperative data, initial parameters of the right ventricle (RV) systolic and diastolic function were assessed. Results. Among the 189 patients, a total of 19 (10.0%) MACE (cardiovascular death, nonfatal myocardial infarction and stroke) were recorded during an 18 month follow up. In patients with the development of MACE during the initial examination, the following changes in RV function were revealed compared with the group without MACE: a decrease in the e’t index (8.2 versus 9.6 cm/s, p = 0.029), an increase in the Et/e’t ratio (5.25 vs. 4.42, p = 0.049) and more frequent presence of RV pseudonormal filling (p = 0.03). In the binary logistic regression analysis, the development of MACE 18 months after CABG was associated with the nonconduction of PCI before surgery, the presence of peripheral atherosclerosis, an increase in IVST and Et/e’t and a decrease in LVEF. Conclusions. RV diastolic dysfunction in the preoperative period was associated with the development of MACE within 18 months after CABG, and the ratio Et/e’t was one of the independent predictors of MACE in a multiple regression analysis. This makes it expedient to include an assessment of not only systolic but also diastolic RV function in the preoperative examination. The inclusion of an assessment of RV diastolic function in the pre-CABG evaluation of patients deserves further study. Full article

We introduce the concepts of extended equimeasurability and extended uniform quasiboundedness in groups of group-valued mappings endowed with a topology that generalizes the topology of convergence in measure. Quantitative characteristics modeled on these concepts allow us to estimate the Hausdorff measure of noncompactness in such a contest. Our results extend and encompass some generalizations of Fréchet–Šmulian and Ascoli–Arzelà compactness criteria found in the literature. Full article

In the present paper, we first introduce different types of fuzzy continuity for mappings between fuzzy F-normed linear spaces and the relations between them are investigated. Secondly, the principles of fuzzy functional analysis are established in the context of fuzzy F-spaces. More precisely, based on the fact that fuzzy continuity and topological continuity are equivalent, we obtain the closed graph theorem and the open mapping theorem. Using Zabreiko’s lemma, we prove the uniform bounded principle and Banach–Steinhaus theorem. Finally, some future research directions are presented. Full article

Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC₅₀ of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC₅₀ of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells. Full article

The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI₅₀ value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI₅₀ ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex. Full article