Induction heating is a frequently used technology in both fundamental and applied research. It is heavily exploited in the industry for processing materials by heat treatments. In addition, it is ...viewed as a promising tool in medicine, particularly as a part of therapeutic strategies for treating cancer diseases. Thus, in order to optimize (i.e., enhance and tune) the performance of the induction heating process, several aspects must be considered, including the design of the magnetic coils, features of the magnetic fields applied, coupling of magnetic and thermal fields, and the material’s characteristics. To tackle this complex problem, numerical mathematical models are often used. The results of which can help in understanding the role of the various parameters on the performance of the induction heating. Here, we present an alternative mathematical approach to solve the induction heating problem using Fredholm integral equations of the second kind with a singular kernel. To reduce the computation time, the Nyström method has been adopted. As the kernel function shows a singularity, a singularity subtraction has been involved in the developed mathematical procedure. Furthermore, the error features of the Nyström method with the singularity subtraction have been described, and convergence conditions of the proposed computational algorithm have been thoroughly identified. Although special conditions for the kernel function and the integration rule are needed, the method shows lower computing times, competing well with those of traditional finite-element based routines. The applicability of the developed methodology is demonstrated for the simulation of induction heating the body of a metal object.
Background
5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the
Bufo alvarius
toad. Inhalation of ...vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited.
Aims
The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience.
Methods
Assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations.
Results
Relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.
Conclusion
A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeO-DMT.
Corneal endothelial dysfunction leads to corneal edema, pain, and vision loss. Adequate animal models are needed to study the safety and efficacy of novel cell therapies as an alternative to corneal ...transplantation.
Primary human corneal endothelial cells (HCECs) were isolated from cadaveric donor corneas, expanded in vitro, transduced to express green fluorescent protein (GFP), loaded with superparamagnetic nanoparticles, and injected into the anterior chamber of adult rabbits immediately after endothelial cell or Descemet's membrane stripping. The same volume of balanced salt solution plus (BSS+) was injected in control eyes. We compared different models for inducing corneal edema in rabbits, and examined the ability of transplanted HCECs to reduce corneal edema over time by measuring central corneal thickness and tracking corneal clarity. GFP-positive donor cells were tracked in vivo using optical coherence tomography (OCT) fluorescence angiography module, and the transplanted cells were confirmed by human nuclei immunostaining.
Magnetic HCECs integrated onto the recipient corneas with intact Descemet's membrane, and donor identity was confirmed by GFP expression and immunostaining for human nuclei marker. Donor HCECs formed a monolayer on the posterior corneal surface and expressed HCEC functional markers of tight junction formation. No GFP-positive cells were observed in the trabecular meshwork or on the iris, and intraocular pressure remained stable through the length of the study.
Our results demonstrate magnetic cell-based therapy efficiently delivers HCECs to restore corneal transparency without detectable toxicity or adverse effect on intraocular pressure. Magnetic delivery of HCECs may enhance corneal function and should be explored further for human therapies.
Essentials
Tumor‐bearing mice were employed to follow oncogenic HRAS sequences in plasma, and blood cells.
Cancer DNA accumulated in leukocytes above levels detected in exosomes, platelets and ...plasma.
Extracellular vesicles and nucleosomes are required for uptake of tumor DNA by leukocytes.
Uptake of tumor‐derived extracellular vesicles by leukocytes triggers coagulant phenotype.
Summary
Background
Tumor‐derived extracellular vesicles (EVs) and free nucleosomes (NSs) carry into the circulation a wealth of cancer‐specific, bioactive and poorly understood molecular cargoes, including genomic DNA (gDNA).
Objective
Here we investigated the distribution of extracellular oncogenic gDNA sequences (HRAS and HER2) in the circulation of tumor‐bearing mice.
Methods and Results
Surprisingly, circulating leukocytes (WBCs), especially neutrophils, contained the highest levels of mutant gDNA, which exceeded the amount of this material recovered from soluble fractions of plasma, circulating EVs, platelets, red blood cells (RBCs) and peripheral organs, as quantified by digital droplet PCR (ddPCR). Tumor excision resulted in disappearance of the WBC‐associated gDNA signal within 2–9 days, which is in line with the expected half‐life of these cells. EVs and nucleosomes were essential for the uptake of tumor‐derived extracellular DNA by neutrophil‐like cells and impacted their phenotype. Indeed, the exposure of granulocytic HL‐60 cells to EVs from HRAS‐driven cancer cells resulted in a selective increase in tissue factor (TF) procoagulant activity and interleukin 8 (IL‐8) production. The levels of circulating thrombin‐antithrombin complexes (TAT) were markedly elevated in mice harboring HRAS‐driven xenografts.
Conclusions
Myeloid cells may represent a hitherto unrecognized reservoir of cancer‐derived, EV/NS‐associated oncogenic gDNA in the circulation, and a possible novel platform for liquid biopsy in cancer. In addition, uptake of this material alters the phenotype of myeloid cells, induces procoagulant and proinflammatory activity and may contribute to systemic effects associated with cancer.
One approach employed in brain–computer interfaces (BCIs) involves the use of steady-state visual evoked potentials (SSVEPs). This article examines the capability of artificial intelligence, ...specifically convolutional neural networks (CNNs), to improve SSVEP detection in BCIs. Implementing CNNs for this task does not require specialized knowledge. The subsequent layers of the CNN extract valuable features and perform classification. Nevertheless, a significant number of training examples are typically required, which can pose challenges in the practical application of BCI. This article examines the possibility of using a CNN in combination with data augmentation to address the issue of a limited training dataset. The data augmentation method that we applied is based on the spectral analysis of the electroencephalographic signals (EEG). Initially, we constructed the spectral representation of the EEG signals. Subsequently, we generated new signals by applying random amplitude and phase variations, along with the addition of noise characterized by specific parameters. The method was tested on a set of real EEG signals containing SSVEPs, which were recorded during stimulation by light-emitting diodes (LEDs) at frequencies of 5, 6, 7, and 8 Hz. We compared the classification accuracy and information transfer rate (ITR) across various machine learning approaches using both real training data and data generated with our augmentation method. Our proposed augmentation method combined with a convolutional neural network achieved a high classification accuracy of 0.72. In contrast, the linear discriminant analysis (LDA) method resulted in an accuracy of 0.59, while the canonical correlation analysis (CCA) method yielded 0.57. Additionally, the proposed approach facilitates the training of CNNs to perform more effectively in the presence of various EEG artifacts.
5-trifluoromethanesulfonyl-uracil (OTfU), a recently proposed radiosensitizer, is decomposed in the gas-phase by attachment of low-energy electrons. OTfU is a derivative of uracil with a triflate ...(OTf) group at the C
-position, which substantially increases its ability to undergo effective electron-induced dissociation. We report a rich assortment of fragments formed upon dissociative electron attachment (DEA), mostly by simple bond cleavages (e.g., dehydrogenation or formation of OTf
). The most favorable DEA channel corresponds to the formation of the triflate anion alongside with the reactive uracil-5-yl radical through the cleavage of the O-C
bond, particularly at about 0 eV. Unlike for halouracils, the parent anion was not detected in our experiments. The experimental findings are accounted by a comprehensive theoretical study carried out at the M06-2X/aug-cc-pVTZ level. The latter comprises the thermodynamic thresholds for the formation of the observed anions calculated under the experimental conditions (383.15 K and 3 × 10
atm). The energy-resolved ion yield of the dehydrogenated parent anion, (OTfU-H)
, is discussed in terms of vibrational Feshbach resonances arising from the coupling between the dipole bound state and vibrational levels of the transient negative ion. We also report the mass spectrum of the cations obtained through ionization of OTfU by electrons with a kinetic energy of 70 eV. The current study endorses OTfU as a potential radiosensitizer agent with possible applications in radio-chemotherapy.
We have previously uncovered the impact of oncogenic and differentiation processes on extracellular vesicles (EVs) in cancer. This is of interested in the context of glioma stem cells (GSC) that are ...responsible for recurrent nature of glioblastoma multiforme (GBM), while retaining the potential to undergo differentiation and self renewal. GSCs reside in vascular niches where they interact with endothelial cells through a number of mediators including bioactive cargo of EVs. GSCs can be classified as proneural (PN) or mesenchymal (MES) subtypes on the basis of their gene expression profiles and distinct biological characteristics. In the present study we investigated how GSC diversity and differentiation programmes influence their EV-mediated communication potentials. Indeed, molecular subtypes of GBMs and GSCs differ with respect to their expression of EV-related genes (vesiculome) and GSCs with PN or MES phenotypes produce EVs with markedly different characteristics, marker profiles, proteomes and endothelial stimulating activities. For example, while EVs of PN GSC are largely devoid of exosomal markers their counterparts from MES GSCs express ample CD9, CD63 and CD81 tetraspanins. In both GSC subtypes serum-induced differentiation results in profound, but distinct changes of cellular phenotypes including the enhanced EV production, reconfiguration of their proteomes and the related functional pathways. Notably, the EV uptake was a function of both subtype and differentiation state of donor cells. Thus, while, EVs produced by differentiated MES GSCs were internalized less efficiently than those from undifferentiated cells they exhibited an increased stimulatory potential for human brain endothelial cells. Such stimulating activity was also observed for EVs derived from differentiated PN GSCs, despite their even weaker uptake by endothelial cells. These findings suggest that the role of EVs as biological mediators and biomarkers in GBM may depend on the molecular subtype and functional state of donor cancer cells, including cancer stem cells.
Abbreviations: CryoTEM: cryo-transmission electron microscopy; DIFF: differentiated GSCs; EGF: epidermal growth factor; DUC: differential ultracentrifugation; EV: extracellular vesicle; FGF: fibroblast growth factor; GBM: glioblastoma multiforme; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSC: glioma stem cells; HBEC-5i: human brain endothelial cells; MES: mesenchymal cells; MTS - 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; PMT1: proneural-to-mesenchyman transition cell line 1; PN: proneural cells; TEM: transmission electron microscopy; WB: western blotting
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