Effect of ALDH1A1 Gene Knockout on Drug Resistance in Paclitaxel and Topotecan Resistant Human Ovarian Cancer Cell Lines in 2D and 3D Model

Ovarian cancer is the most common cause of gynecological cancer death. Cancer Stem Cells (CSCs) characterized by drug transporters and extracellular matrix (ECM) molecules expression are responsible for drug resistance development. The goal of our study was to examine the role of aldehyde dehydrogenase 1A1 (ALDH1A1) expression in paclitaxel (PAC) and topotecan (TOP) resistant ovarian cancer cell lines. In both cell lines, we knocked out the ALDH1A1 gene using the CRISPR/Cas9 technique. Additionally, we derived an ALDH1A1 positive TOP-resistant cell line with ALDH1A1 expression in all cells via clonal selection. The effect of ALDH1A1 gene knockout or clonal selection on the expression of ALDH1A1, drug transporters (P-gp and BCRP), and ECM (COL3A1) was determined by Q-PCR, Western blot and immunofluorescence. Using MTT assay, we compared drug resistance in two-dimensional (2D) and three-dimensional (3D) cell culture conditions. We did not observe any effect of ALDH1A1 gene knockout on MDR1/P-gp expression and drug resistance in the PAC-resistant cell line. The knockout of ALDH1A1 in the TOP-resistant cell line resulted in a moderate decrease of BCRP and COL3A1 expression and weakened TOP resistance. The clonal selection of ALDH1A1 cells resulted in very strong downregulation of BCPR and COL3A1 expression and overexpression of MDR1/P-gp. This finally resulted in decreased resistance to TOP but increased resistance to PAC. All spheroids were more resistant than cells growing as monolayers, but the resistance mechanism differs. The spheroids’ resistance may result from the presence of cell zones with different proliferation paces, the density of the spheroid, ECM expression, and drug capacity to diffuse into the spheroid.     

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

Applicability of Field Plate in Double Channel GaN HEMT for Radio-Frequency and Power-Electronic Applications

Silicon - In the present communication, for the first time, applicability of Field Plate (FP) for Double Channel (DC) AlGaN/GaNHEMT is demonstrated. Impact of design space parameters such as field...     

Structural studies of poly(butyl acrylate) - poly(ethylene oxide) miktoarm star polymers

Structural behavior of miktoarm star polymers comprising poly(butyl acrylate) (PBA) and poly(ethylene oxide) (PEO) arms was studied by means of Differential Scanning Calorimetry (DSC), Wide Angle X-Ray Scattering (WAXS), Polarized Optical Microscopy (POM) and Fourier Transform Infrared Spectroscopy (FTIR) methods. The aim of this study was to correlate changes in the composition of the arms of the PBA/PEO miktoarm star polymers with their structures. As a consequence of increasing PBA content, the decrease in crystallinity of the studied PBA/PEO heteroarm star copolymers was observed. Regardless of the copolymer composition, fraction of oxyethylene units in the crystalline PEO phase was similar in all investigated systems. The POM images showed spherulitic morphology of the materials having low PBA content, while an increase in PBA arms fraction leads to the formation of less ordered structures. The analysis of FTIR vibrational spectrum indicates helical conformation of PEO chains in the crystalline phase. Isothermal crystallization studies carried out using the FTIR technique suggest the existence of isolated domains in the nanoscopic scale of investigated materials.     

Behavior of Anionic Surfactants and Short Chain Alcohols Mixtures in the Monolayer at the Water–Air Interface

Measurements of the surface tension of aqueous solution of mixtures of sodium dodecyl sulfate (SDDS) with methanol and ethanol in SDDS concentration range from 10⁻⁵ to 10⁻² M and mixtures of sodium hexadecyl sulfonate (SHS) with methanol and ethanol at SHS concentration from 10⁻⁵ to 8 × 10⁻⁴ M and for methanol and ethanol from 0 to 21.1 and, 11.97 M, respectively, were carried out at 293 K. Moreover, the surface tension of aqueous solution mixtures of SDDS with propanol in the concentration range from 0 to 6.67 M taken from the literature was also considered. The results obtained indicate that it is possible to describe the relationship between the surface tension and molar concentration or molar fraction of alcohol by Szyszkowski and Connors equations. However, the Fainerman and Miller equation allows us to predict the isotherm of the surfactant tension at constant anionic surfactants concentration at which their molecules are present in the solution in the monomeric form if the molar area of surfactants and alcohols can be determined. Based on the surface tension isotherms, the Gibbs surface excess of anionic surfactants and alcohols concentration at water–air interface was determined and then recalculated for Guggenheim-Adam surface excess concentration of these substrates, and next the molar fraction of alcohols and surfactants in the surface layer was determined. These molar fractions were discussed with regard to surfactant and alcohol standard free energy of adsorption at the water–air interface determined from Langmuir and Aronson and Rosen equations. The standard free energy of adsorption determined in these ways was compared to that deduced on the basis of pC₂₀ and Lifshitz van der Waals-components of the anionic surfactant and alcohol tails.     

Behavior of Cetyltrimethylammonium Bromide, tert-Octylphenol (9.5 EO) Ethoxylate and Ethanol Mixtures at the Water–Air Interface

The surface tension measurements of aqueous solutions of p‐(1,1,3,3‐tetramethylbutyl)phenoxypoly(9.5)ethylene glycol or tert‐octylphenol ethoxylate (TOP10) and cetyltrimethylammonium bromide (CTAB) mixtures with ethanol were carried out in the range of the total concentration of CTAB and TOP10 mixtures from 1 × 10^?7 to 1 × 10^?2 M and ethanol from 0 to 17.13 M. In the CTAB and TOP10 mixtures, the mole fractions of TOP10 were equal to 0.2; 0.4; 0.6; and 0.8, respectively. The results obtained were compared to those calculated from the Fainerman and Miller equation developed for ideal mixtures of two homologous surfactants, as well as from the Connors equation derived for the concentrated organic solutions. The calculations of the surface tension from the Fainerman and Miller equation were carried out treating the solvent and solute in a few different ways. The differences between the measured and calculated values of the surface tension were discussed in the light of molecular interaction parameter and the composition of the surface layer. The composition of the mixed surface layer at the solution‐air interface was evaluated according to Rosen using the nonideal solution theory with the assumption that water with ethanol is a mixed solvent. Knowing the values of mole fractions of CTAB and TOP10 in the surface layer, the molecular interaction parameter was determined.     

Development of monolithic porous composites using carbonized coals as block porous supports, and poly(furfuryl alcohol) and chitosan as fillers

In this study, monolithic block cokes have been used as supports to develop carbon–carbon and carbon–polymer monolithic block composites using poly(furfuryl alcohol) and chitosan as fillers. Cokes were produced from single coals and coal blends by carbonization at 950 °C. The supports and the resultant composites were characterized by means of elemental analysis (carbon, hydrogen and nitrogen—CHN), low-temperature physical adsorption of nitrogen, gas helium densitometry, electric and ultrasonic measurements. Morphology of the supports and the composites was observed using scanning electronic microscope. The supports were found to be porous carbon materials of high C content within the range of 97.6–98.5 wt%, of porous structure characterized by macropores, with low contribution of mesopores with diameters of 17–25 nm. The resultant composites were found to be porous light materials with apparent density of less than 1 g/cm³, and bulk porosity ranging from 35 to 54 %, with high stiffness evidenced by dynamic elastic moduli reaching values up to ~5 GPa. Addition of the polymers to the cokes (block supports) was found to worsen electrical properties giving the electrical conductivity values ranging from 0.2 to 0.5 S/cm for all composites studied.     

Wire configuration creating a uniform magnetic field

Contents In this paper the magnetic field created by a direct current flowing in the wires distributed on the surface of an elliptic cylinder is determined. The wire configuration is surrounded by a ferromagnetic ring having arbitrary magnetic permeability . Magnetic field patterns are shown, assuming infinite permeability of the ferromagnetic, and for the case of absence of the ferromagnetic, i.e. for =₀. The separation-of-variables method has been used.

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Übersicht In der Arbeit wird das magnetische Feld gleichstromdurchflossener gerader Leiter bestimmt, die in einem elliptischen Hohlzylinder parallel zu dessen Achse untergebracht sind. Die Anordnung ist von einem ferromagnetischen Ring umgeben, der beliebige Permeabilität aufweist. Für den Fall des hochpermeablen Ringes oder der Abwesenheit des ferromagnetischen Stoffes werden die Verteilungen des magnetischen Feldes angegeben. Die Methode der Trennung der Variablen wird benutzt.