Search Results (22)

This paper presents the design of a permanent-magnet-assisted synchronous reluctance motor (PMa-SynRM) for compressor applications using Sm-series injection-molded magnets that eliminate heavy rare-earth elements. The high shape flexibility of the injection-molded magnets enables the formation of a curved multi-layer flux-barrier rotor geometry based on the Joukowski airfoil potential, optimizing magnetic flux flow under typical compressor operating conditions. Furthermore, electromagnetic performance, irreversible demagnetization behavior, and rotor stress sensitivity were analyzed with respect to key design variables to derive a model that satisfies the target performance requirements. The validity of the proposed design was confirmed through finite element method (FEM) comparisons with a conventional IPMSM using sintered NdFeB magnets, demonstrating the feasibility of HRE-free PMa-SynRM for high-performance compressor drives. Full article

Closed-Kinematic Chain Manipulators (CKCM) have gained attention due to their precise Cartesian motion capability through coordinated active joint movements. Furthermore, ensuring synchronization among the joints of CKCMs is critical for reliable operation. An advanced control scheme for CKCMs that combines Nonsingular Fast Terminal Sliding Mode Control (NFTSMC) with Time Delay Estimation (TDE) while utilizing synchronization errors, namely Syn-TDE-NFTSMC, to effectively address joint errors in CKCMs was developed. NFTSMC enables fast convergence through nonlinear terminal sliding while TDE eliminates the need for prior knowledge of the robot’s dynamics, thereby simplifying its implementation and reducing its computational requirements. It is known that the inclusion of TDE reduces about 98% of the computational requirement of control schemes without TDE. The newly developed control scheme was rigorously evaluated using computer simulation and its control performance was compared with that of existing control methods. This paper presents an experimental study where the newly developed control scheme and other existing control schemes were applied to a real CKCM with 2 degrees of freedom (DOF). The experimental results confirm that the control scheme performed much better than other existing control schemes in terms of synchronization and control performance, achieving a reduction in maximum tracking errors of up to 81% as compared to other existing control schemes. The results confirm the efficacy of the newly developed control scheme in enhancing control precision and system stability, making it a promising solution for improving CKCM control strategies in real-world applications. Full article

Currently, electric machines predominantly rely on costly rare-earth NdFeB magnets, which pose both economic and environmental challenges due to rising demand. This research explores recent advancements in machine topologies and magnetic materials to identify and assess promising solutions to this issue. The study investigates two alternative machine topologies to the conventional permanent magnet synchronous machine (PMSM): the permanent magnet-assisted synchronous reluctance machine (PMaSynRM), which reduces magnet usage, and the wound-field synchronous machine (WFSM), which eliminates magnets entirely. Additionally, the potential of ferrite and recycled NdFeB magnets as substitutes for primary NdFeB magnets is evaluated. Through detailed simulations, the study compares the performance and cost-effectiveness of these solutions against a reference permanent magnet synchronous machine (PMSM). Given their promising performance characteristics and potential to reduce or eliminate the use of rare-earth materials in next-generation electric machines, it is recommended that future research should focus on novel topologies like hybrid-excitation, axial-flux, and switched reluctance machines with an emphasis on manufacturability and also novel magnetic materials such as FeN and MnBi that are currently seeing synthesis challenges. Full article

Selenoxide syn elimination is a widely used method for the synthesis of alkenes because it proceeds under exceptionally mild conditions, typically with excellent regio- and stereoselectivity. Surprisingly, hetero-selenoxide eliminations, where one or both olefinic carbon atoms are replaced with heteroatoms, have been little investigated, and their selenonyl counterparts even less so. A variety of such reactions, where the heteroatoms included combinations of O, N and S, as well as C, were investigated computationally. Selenoxides typically have lower activation energies and are slightly endothermic, while the corresponding selenones display higher activation energies and are exothermic in the gas state. The results are consistent with concerted, five-centre processes, leading to the formation of dioxygen, aldehydes, diazenes and imines from seleninyl or selenonyl peroxides, esters, hydrazines and amines, respectively. The more acidic selenenyl hydrodisulfide analogue undergoes proton transfer to the basic selenoxide oxygen atom instead of concerted elimination, resulting in the formation of a zwitterion. However, the formation of the corresponding selenonyl zwitterion is disfavoured compared to concerted syn elimination. The effects of solvents were also computed along with changes in enthalpy, entropy and free energy. Solvent effects were variable, while free energy calculations indicated overall ΔG values ranging between 3.60 and −32.12 kcal mol⁻¹ for the syn eliminations of methyl methanethioseleninate and methaneperoxyselenonic acid, respectively. These computations suggest that the olefin-forming selenoxide syn elimination may be more general than currently understood and that replacement of the two carbon atoms with heteroatoms can lead to viable processes. Full article

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.8 within 70 min at 40 °C with 5 ng/mL limit of detection for all investigated analytes. It was shown that cyanoacetohydrazide derivatives produces both syn- and anti-forms as well as hydroxylamine, and their ratios were evaluated and shown in presented work. An efficiency enchantment from two to up to five times was achieved with a novel derivatization reagent. Its applicability for qualitative analysis of steroids in urine was presented at real samples. Additionally, the reproducible fragmentation of the derivatizing agent in collision-induced dissociation offers opportunities for simplified non-targeted steroidomic screening. Furthermore, cyanoacetohydrazide increases ionization efficiency in positive mode, which can eliminate the need for redundant high-resolution instrument runs required for both positive and negative mode analyses. Full article

2,6-Diaryl-4H-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S-oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones, and their S-sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei, Trypanosoma cruzi, and various Leishmania species in comparison with their cytotoxicity against human fibroblasts hMRC-5. The data revealed that the sulfides, sulfoxides, and sulfones, in which the Michael acceptor sites are temporarily masked, are less toxic against mammal cells while the anti-trypanosomal potency was maintained against T. b. brucei, T. cruzi, L. infantum, and L. donovani, thus confirming the validity of the prodrug strategy. The mechanism of action is proposed to be due to the involvement of diarylideneacetones in cascades of redox reactions involving the trypanothione system. After Michael addition of the dithiol to the double bonds, resulting in an elongated polymer, the latter—upon S-oxidation, followed by syn-eliminations—fragments, under continuous release of reactive oxygen species and sulfenic/sulfonic species, causing the death of the trypanosomal parasites in the micromolar or submicromolar range with high selectivity indexes. Full article

Availability of PET imaging radiotracers targeting α-synuclein aggregates is important for early diagnosis of Parkinson’s disease and related α-synucleinopathies, as well as for the development of new therapeutics. Derived from a pyrazole backbone, ¹¹C-labelled derivatives of anle138b (3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole)—an inhibitor of α-synuclein and prion protein oligomerization—are currently in active development as the candidates for PET imaging α-syn aggregates. This work outlines the synthesis of a radiotracer based on the original structure of anle138b, labelled with fluorine-18 isotope, eminently suitable for PET imaging due to half-life and decay energy characteristics (97% β+ decay, 109.7 min half-life, and 635 keV positron energy). A three-step radiosynthesis was developed starting from 6-[¹⁸F]fluoropiperonal (6-[¹⁸F]FP) that was prepared using (piperonyl)(phenyl)iodonium bromide as a labelling precursor. The obtained 6-[¹⁸F]FP was used directly in the condensation reaction with tosylhydrazide followed by 1,3-cycloaddition of the intermediate with 3′-bromophenylacetylene eliminating any midway without any intermediate purifications. This one-pot approach allowed the complete synthesis of [¹⁸F]anle138b within 105 min with RCY of 15 ± 3% (n = 3) and A_m in the range of 32–78 GBq/µmol. The [¹⁸F]fluoride processing and synthesis were performed in a custom-built semi-automated module, but the method can be implemented in all the modern automated platforms. While there is definitely space for further optimization, the procedure developed is well suited for preclinical studies of this novel radiotracer in animal models and/or cell cultures. Full article

Many neurodegenerative disorders are characterized by the abnormal aggregation of misfolded proteins that form amyloid deposits which possess prion-like behavior such as self-replication, intercellular transmission, and consequent induction of native forms of the same protein in surrounding cells. The distribution of the accumulated proteins and their correlated toxicity seem to be involved in the progression of nervous system degeneration. Molecular chaperones are known to maintain proteostasis, contribute to protein refolding to protect their function, and eliminate fatally misfolded proteins, prohibiting harmful effects. However, chaperone network efficiency declines during aging, prompting the onset and the development of neurological disorders. Extracellular vesicles (EVs) are tiny membranous structures produced by a wide range of cells under physiological and pathological conditions, suggesting their significant role in fundamental processes particularly in cellular communication. They modulate the behavior of nearby and distant cells through their biological cargo. In the pathological context, EVs transport disease-causing entities, including prions, α-syn, and tau, helping to spread damage to non-affected areas and accelerating the progression of neurodegeneration. However, EVs are considered effective for delivering therapeutic factors to the nervous system, since they are capable of crossing the blood–brain barrier (BBB) and are involved in the transportation of a variety of cellular entities. Here, we review the neurodegeneration process caused mainly by the inefficiency of chaperone systems as well as EV performance in neuropathies, their potential as diagnostic biomarkers and a promising EV-based therapeutic approach. Full article

Nanoscale control of chemical reactivity, manipulation of reaction pathways, and ultimately driving the outcome of chemical reactions are quickly becoming reality. A variety of tools are concurring to establish such capability. The confinement of guest molecules inside nanoreactors, such as the hollow nanostructures of carbon nanotubes (CNTs), is a straightforward and highly fascinating approach. It mechanically hinders some molecular movements but also decreases the free energy of translation of the system with respect to that of a macroscopic solution. Here, we examined, at the quantum mechanics/molecular mechanics (QM/MM) level, the effect of confinement inside CNTs on nucleophilic substitution (S_N2) and elimination (syn-E2 and anti-E2) using as a model system the reaction between ethyl chloride and chloride. Our results show that the three reaction mechanisms are kinetically and thermodynamically affected by the CNT host. The size of the nanoreactor, i.e., the CNT diameter, represents the key factor to control the energy profiles of the reactions. A careful analysis of the interactions between the CNTs and the reactive system allowed us to identify the driving force of the catalytic process. The electrostatic term controls the reaction kinetics in the S_N2 and syn/anti-E2 reactions. The van der Waals interactions play an important role in the stabilization of the product of the elimination process. Full article

Enzyme-mediated processes have proven to be a valuable and sustainable alternative to traditional chemical methods. In this regard, the use of multi-enzymatic systems enables the realization of complex synthetic schemes, while also introducing a number of additional advantages, including the conversion of reversible reactions into irreversible processes, the partial or complete elimination of product inhibition problems, and the minimization of undesirable by-products. In addition, the immobilization of biocatalysts on magnetic supports allows for easy reusability and streamlines the downstream process. Herein we have developed a cascade system for cladribine synthesis based on the sequential action of two magnetic biocatalysts. For that purpose, purine 2′-deoxyribosyltransferase from Leishmania mexicana (LmPDT) and Escherichia coli hypoxanthine phosphoribosyltransferase (EcHPRT) were immobilized onto Ni²⁺-prechelated magnetic microspheres (MagReSyn^®NTA). Among the resulting derivatives, MLmPDT3 (activity: 11,935 IU/g_support, 63% retained activity, operational conditions: 40 °C and pH 5–7) and MEcHPRT3 (12,840 IU/g_support, 45% retained activity, operational conditions: pH 5–8 and 40–60 °C) emerge as optimal catalysts for further synthetic application. Moreover, the MLmPDT3/MEcHPRT3 system was biochemically characterized and successfully applied to the one-pot synthesis of cladribine under various conditions. This methodology not only displayed a 1.67-fold improvement in cladribine synthesis (compared to MLmPDT3), but it also implied a practically complete transformation of the undesired by-product into a high-added-value product (90% conversion of Hyp into IMP). Finally, MLmPDT3/MEcHPRT3 was reused for 16 cycles, which displayed a 75% retained activity. Full article

The complexity and overall burden of Parkinson’s disease (PD) require new pharmacological approaches to counteract the symptomatology while reducing the progressive neurodegeneration of affected dopaminergic neurons. Since the pathophysiological signature of PD is characterized by the loss of physiological levels of dopamine (DA) and the misfolding and aggregation of the alpha-synuclein (α-syn) protein, new proposals seek to restore the lost DA and inhibit the progressive damage derived from pathological α-syn and its impact in terms of oxidative stress. In this line, nanomedicine (the medical application of nanotechnology) has achieved significant advances in the development of nanocarriers capable of transporting and delivering basal state DA in a controlled manner in the tissues of interest, as well as highly selective catalytic nanostructures with enzyme-like properties for the elimination of reactive oxygen species (responsible for oxidative stress) and the proteolysis of misfolded proteins. Although some of these proposals remain in their early stages, the deepening of our knowledge concerning the pathological processes of PD and the advances in nanomedicine could endow for the development of potential treatments for this still incurable condition. Therefore, in this paper, we offer: (i) a brief summary of the most recent findings concerning the physiology of motor regulation and (ii) the molecular neuropathological processes associated with PD, together with (iii) a recapitulation of the current progress in controlled DA release by nanocarriers and (iv) the design of nanozymes, catalytic nanostructures with oxidoreductase-, chaperon, and protease-like properties. Finally, we conclude by describing the prospects and knowledge gaps to overcome and consider as research into nanotherapies for PD continues, especially when clinical translations take place. Full article

This work proposes a new system capable of real-time ship instance segmentation during maritime surveillance missions by unmanned aerial vehicles using an onboard standard RGB camera. The implementation requires two stages: an instance segmentation network able to produce fast and reliable preliminary segmentation results and a post-processing 3D fully connected Conditional Random Field, which significantly improves segmentation results by exploring temporal correlations between nearby frames in video sequences. Moreover, due to the absence of maritime datasets consisting of properly labeled video sequences, we create a new dataset comprising synthetic video sequences of maritime surveillance scenarios (MarSyn). The main advantages of this approach are the possibility of generating a vast set of images and videos, being able to represent real-world scenarios without the necessity of deploying the real vehicle, and automatic labels, which eliminate human labeling errors. We train the system with the MarSyn dataset and with aerial footage from publicly available annotated maritime datasets to validate the proposed approach. We present some experimental results and compare them to other approaches, and we also illustrate the temporal stability provided by the second stage in missing frames and wrong segmentation scenarios. Full article

Acute myeloid leukemia (AML) is one of the most common hematological malignancies with high heterogeneity, characterized by a differentiating block at the early progenitor stage. The selective BCL-2 inhibitor, Venetoclax (Ven), has shown exciting clinical results in a certain group of AML patients. However, Ven alone is insufficient to reach an enduringly complete response, which leads to the concern of Ven resistance. Alternative combined therapies with Ven are demanded in AML. Here, we reported the synergistic effect and molecular mechanism of the enhancer of zeste homolog 2 (EZH2) inhibitor DZNeP with Ven in AML cells. Results showed that the combination of DZNeP with Ven significantly induces cell proliferation arrest compared to single-drug control in AML cells and primary samples, and CalcuSyn analysis showed their significant synergy. The combination also significantly promotes apoptosis and increases the expression of pro-apoptotic proteins. The whole transcriptome analysis showed that phosphoinositide-3-kinase-interacting protein1 (PIK3IP1), the PI3K/AKT/mTOR signaling suppressor, is upregulated upon DZNeP treatment. Moreover, EZH2 is upregulated but PIK3IP1 is downregulated in 88 newly diagnosed AML cohorts compared to 70 healthy controls, and a higher expression of EZH2 is associated with poor outcomes in AML patients. Particularly, the combination of DZNeP with Ven dramatically eliminated CD117 (c-KIT) (+) AML blasts, suggesting the effect of the combination on tumor stem cells. In summary, our data indicated that DZNeP increases the sensitivity of Ven in AML by affecting PI3K and c-KIT signaling in AML. Our results also suggested that the therapeutic targeting of both EZH2 and BCL-2 provides a novel potential combined strategy against AML. Full article

The limitations of gemcitabine (GEM) in cancer therapy are due to its poor pharmacokinetics, which cause undesired adverse effects. The current study was aimed at investigating the anticancer effect and apoptotic mechanism of synthesized nanoemulsion (NE) containing Pulicaria crispa essential oil (PC-EO) and GEM (PC-NE:GEM) on MCF-7 and Hep-G2 cancer cell lines. An optimized NE formulation was selected based on the Box–Behnken method. The droplet size of the optimized PC-NE was 9.93 ± 0.53 nm, but after GEM loading, it was increased to 11.36 ± 0.0.21 nm. Results from FTIR revealed that GEM was successfully loaded onto PC-NE. The antineoplastic effect of PC-NE:GEM on MCF-7 and Hep-G2 cancer cells was increased more than 100-fold relative to that of GEM. A combination index and isobologram based on CompuSyn software revealed the synergistic effect of the formulation produced by a 1:1 ratio combination of PC-NE and GEM. These findings were confirmed by examination of cellular morphologies. The combination formulation strongly induced about 4.48-fold and 2.95-fold increases in apoptosis in MCF-7 and Hep-G2 cells, respectively, when compared with GEM. Moreover, PC-NE:GEM produced a synergistic increase in ROS production in MCF-7 cells (15.23%) and Hep-G2 cells (31.69%), when compared with GEM. In addition, PC-NE:GEM enhanced the activation of the intrinsic apoptosis pathway through upregulation of expressions of p53 and Caspase-3, and downregulation of Bcl-2 expression in MCF-7 cells, while the expressions of Caspase-3, Bax, and p53 were upregulated in HepG2 cells. These results indicate that the GEM-loaded NE containing PC-EO may reduce the dose of GEM and eliminate the associated side effects. Full article

This paper proposes a modelling technique for Synchronous Reluctance Motors (SynRMs) based on a generalized Magnetic Equivalent Circuit (MEC). The proposed model can be used in the design of any number of stator teeth, rotor poles, and rotor barrier combinations. This technique allows elimination of infeasible machine solutions during the initial machine sizing stage, resulting in a lower cohort of feasible machine solutions that can be further optimized using finite element methods. Therefore, saturation effects, however, are not considered in the modelling. This paper focuses on modelling a generic structure of the SynRM in modular form and is then extended to a full SynRM model. The proposed model can be iteratively used for any symmetrical rotor pole and stator teeth combination. The developed technique is applied to model a 4-pole, 36 slot SynRM as an example, and the implemented model is executed following a time stepping strategy. The motor characteristics such as flux distribution and torque of the developed SynRM model is compared with finite elemental analysis (FEA) simulation results. Full article