Combining Embeddings of Input Data for Text Classification

Neural Processing Letters - The problem of automatic text classification is an essential part of text analysis. The improvement of text classification can be done at different levels such as a...     

Nanoprecipitation-assisted ion current oscillations

Nanoscale pores exhibit transport properties that are not seen in micrometre-scale pores, such as increased ionic concentrations inside the pore relative to the bulk solution, ionic selectivity and ionic rectification. These nanoscale effects are all caused by the presence of permanent surface charges on the walls of the pore. Here we report a new phenomenon in which the addition of small amounts of divalent cations to a buffered monovalent ionic solution results in an oscillating ionic current through a conical nanopore. This behaviour is caused by the transient formation and redissolution of nanoprecipitates, which temporarily block the ionic current through the pore. The frequency and character of ionic current instabilities are regulated by the potential across the membrane and the chemistry of the precipitate. We discuss how oscillating nanopores could be used as model systems for studying nonlinear electrochemical processes and the early stages of crystallization in sub-femtolitre volumes. Such nanopore systems might also form the basis for a stochastic sensor.     

Digitally Alloyed Modulated Precursor Flow Epitaxial Growth of Ternary AlGaN with Binary AlN and GaN Sub-Layers and Observation of Compositional Inhomogeneity

We report the growth of ternary aluminum gallium nitride (AlGaN) layers on AlN/sapphire template/substrates by digitally alloyed modulated precursor flow epitaxial growth (DA-MPEG), which combined an MPEG AlN sub-layer with a conventional metalorganic chemical vapor deposition (MOCVD)-grown GaN sub-layer. The overall composition in DA-MPEG Al _x Ga_1−x N was controlled by adjustment of the growth time (i.e., the thickness) of the GaN sub-layer. As the GaN sub-layer growth time increased, the Al composition in AlGaN decreased to 50%, but the surface morphology of the AlGaN layer became rough, and a three-dimensional structure with islands appeared for the DA-MPEG AlGaN with relatively thick GaN sub-layers, possibly resulting from the Ga adatom surface migration behavior and/or the strain built up from lattice mismatch between AlN and GaN sub-layers with increasing GaN sub-layer growth time. Through strain analysis by high-resolution x-ray diffraction, reciprocal space mapping, and scanning transmission electron microscopy, it was found that there was compositional inhomogeneity in the DA-MPEG AlGaN with AlN and GaN binary sub-layers for the case of the layer with relatively thick GaN sub-layers.     

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies

Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Studies on possible interactions between statins and human proteins could provide a deeper insight into the pleiotropic and adverse effects of these drugs. Adenylate kinase (AK) was found to regulate HDL endocytosis, cellular metabolism, cardiovascular function and neurodegeneration. In this work, we investigated interactions between human adenylate kinase isoenzyme 1 (hAK1) and atorvastatin (AVS), fluvastatin (FVS), pravastatin (PVS), rosuvastatin (RVS) and simvastatin (SVS) with fluorescence spectroscopy. The tested statins quenched the intrinsic fluorescence of hAK1 by creating stable hAK1-statin complexes with the binding constants of the order of 10⁴ M⁻¹. The enzyme kinetic studies revealed that statins inhibited hAK1 with significantly different efficiencies, in a noncompetitive manner. Simvastatin inhibited hAK1 with the highest yield comparable to that reported for diadenosine pentaphosphate, the only known hAK1 inhibitor. The determined AK sensitivity to statins differed markedly between short and long type AKs, suggesting an essential role of the LID domain in the AK inhibition. Our studies might open new horizons for the development of new modulators of short type AKs.     

UVA Radiation Enhances Lomefloxacin-Mediated Cytotoxic,Growth-Inhibitory and Pro-Apoptotic Effect in Human Melanoma Cells through Excessive Reactive Oxygen Species Generation

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells’ viability in a concentration-dependent manner. This effect significantly intensified when melanoma cells were exposed to UVA irradiation and the drug. For melanoma cells exposed to lomefloxacin or lomefloxacin co-treatment with UVA irradiation, the concentrations of the drug that decreased the cells’ viability by 50% (EC₅₀) were found to be 0.97, 0.17, 1.01, 0.18 mM, respectively. Moreover, we found that the redox imbalance, mitochondrial membrane potential breakdown, induction of DNA fragmentation, and changes in the melanoma cells’ cell cycle distribution (including G₂/M, S as well as Sub-G₁-phase blockade) were lomefloxacin in a dose-dependent manner and were significantly augmented by UVA radiation. This is the first experimental work that assesses the impact of excessive reactive oxygen species generation upon UVA radiation exposure on lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effects towards human melanoma cells, indicating the possibility of the usage of this drug in the photochemotherapy of malignant melanoma as an innovative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells.     

Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes

Malignant melanoma is responsible for the majority of skin cancer-related deaths. The methods of cancer treatment include surgical removal, chemotherapy, immunotherapy, and targeted therapy. However, neither of these methods gives satisfactory results. Therefore, the development of new anticancer therapeutic strategies is very important and may extend the life span of people suffering from melanoma. The aim of this study was to examine the effect of ketoprofen (KTP) and UVA radiation (UVAR) therapy on cell proliferation, apoptosis, and cell cycle distribution in both melanotic melanoma cells (COLO829) and human melanocytes (HEMn-DP) in relation to its supportive effect in the treatment of melanoma. The therapy combining the use of pre-incubation with KTP and UVAR causes a significant increase in the anti-proliferative properties of ketoprofen towards melanoma cells and the co-exposure of melanotic melanoma cells induced apoptosis shown as the mitochondrial membrane breakdown, cell-cycle deregulation, and DNA fragmentation. Moreover, co-treatment led to GSH depletion showing its pro-apoptotic effect dependent on ROS overproduction. The treatment did not show a significant effect on normal cells—melanocytes—which indicates its high selectivity. The results suggest a possible benefit from the use of the ketoprofen and ultraviolet A irradiation as a new concept of melanotic melanoma therapy.