Targeting Mitochondrial Metabolism in Clear Cell Carcinoma of the Ovaries

Ovarian clear cell carcinoma (OCCC) is a rare but chemorefractory tumor. About 50% of all OCCC patients have inactivating mutations of ARID1A, a member of the SWI/SNF chromatin-remodeling complex. Members of the SWI/SNF remodeling have emerged as regulators of the energetic metabolism of mammalian cells; however, the role of ARID1A as a modulator of the mitochondrial metabolism in OCCCs is yet to be defined. Here, we show that ARID1A loss results in increased mitochondrial metabolism and renders ARID1A-mutated cells increasingly and selectively dependent on it. The increase in mitochondrial activity following ARID1A loss is associated with increase in c-Myc expression and increased mitochondrial number and reduction of their size consistent with a higher mitochondrial cristae/outer membrane ratio. Significantly, preclinical testing of the complex I mitochondrial inhibitor IACS-010759 showed it extends overall survival in a preclinical model of ARID1A-mutated OCCC. These findings provide for the targeting mitochondrial activity in ARID1A-mutated OCCCs.     

Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1) assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho- to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide (2), and 2-hydroxy-N-(4-nitrophenyl)-naphthalene-1-carboxamide (6) showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.     

Electric and Kinetic Properties of Screen-Printed Strontium Titanate Films at High Temperatures

By eliminating the admixture of glass components to the original powder when making the paste, screen-printed structures can be produced from strontium titanate with reproducible properties. The ways that the film structure and the temperature profile affect the dependence of the electric conductivity on the oxygen partial pressure during the burn-in process are examined. The consequences of the surface/volume ratio of the grain structures on the response behavior of SrTiO₃ layers during rapid changes in oxygen partial pressure are investigated. Possible influences of the composition of grain boundaries on conductivity characteristics and the time-governing steps of the interaction between oxygen vacancies in the lattice and the oxygen molecules of the gaseous environment are also discussed.     

Czech primary radon measurement equipment

The Authorized Metrological Centre (AMS) working by SUJCHBO (National Institute for Nuclear, Chemical and Biological Protection) ensures for the Czech Republic the metrological traceability for devices that measure the radon concentration and the energy equivalent radon concentration connected with the radon decay products (RnDP). The evaluation and the calibration of measuring devices for radon and RnDP require the stable conditions (first of all radon and the RnDP concentrations). The new AMS radon-aerosol chamber in Kamenná consists of the walk-in testing chamber with a volume of 10 m(3) and of the handling box with a volume of 0.3 m(3). The design of the chamber allows measurement and a control of environmental parameters such as the temperature, the pressure of air inside and outside of the chamber, the relative humidity of air, the concentration and the size distribution of aerosol particles and the air velocity.     

A silica sol-gel design strategy for nanostructured metallic materials

Batteries, fuel cells and solar cells, among many other high-current-density devices, could benefit from the precise meso- to macroscopic structure control afforded by the silica sol-gel process. The porous materials made by silica sol-gel chemistry are typically insulators, however, which has restricted their application. Here we present a simple, yet highly versatile silica sol-gel process built around a multifunctional sol-gel precursor that is derived from the following: amino acids, hydroxy acids or peptides; a silicon alkoxide; and a metal acetate. This approach allows a wide range of biological functionalities and metals--including noble metals--to be combined into a library of sol-gel materials with a high degree of control over composition and structure. We demonstrate that the sol-gel process based on these precursors is compatible with block-copolymer self-assembly, colloidal crystal templating and the St?ber process. As a result of the exceptionally high metal content, these materials can be thermally processed to make porous nanocomposites with metallic percolation networks that have an electrical conductivity of over 1,000 S cm(-1). This improves the electrical conductivity of porous silica sol-gel nanocomposites by three orders of magnitude over existing approaches, opening applications to high-current-density devices.     

Scanning iron temperature lidar for mesopause temperature observation

We introduce a new method for temperature profile measurements in the mesopause region in the altitude range from 80 to 105 km. A frequency-doubled narrowband alexandrite laser is used to scan the iron resonance line at 386 nm. The isotopic shifts of the iron isotopes and the laser bandwidth are derived by the measurement itself. Neglecting the minor isotopes results in large temperature errors up to 28 K. We discuss the derived temperatures in comparison with results of our potassium temperature lidar. The iron lidar-derived temperatures have typically a statistical error of 0.4 K and vary by less than 10 K, which is due to the daily natural variation. The all-solid-state system, which is compact, can be containerized and deployed at remote locations.     

Cooking oils and fat waste collection infrastructure planning: a regional-level outline

Clean Technologies and Environmental Policy - Among the current trends in waste management and circular economy is the involvement of new fractions of waste for sorting and collection. One of them...     

Liquid nitrogen energy storage unit

An energy storage unit is a device able to store thermal energy with a limited temperature drift. After precooling such unit with a cryocooler it can be used as a temporary cold source if the cryocooler is stopped or as a thermal buffer to attenuate temperature fluctuations due to heat bursts. In this article, after a brief study of the possible solutions for such devices, we show that a low temperature cell filled with liquid nitrogen and coupled to a room temperature expansion volume offers the most compact and light solution in the temperature range 60–80 K. For instance, a low temperature cell as small as 23 cm³ allows the storage of 3.7 kJ between 76 K and 81 K. Experimental results were obtained varying the expansion volume size, the filling pressure and the temperature range. These results agree with our simple model based on thermodynamical properties of nitrogen. A cell filled with porous material was tested to confine the liquid in the cell independently of the gravity. This material enhances the thermal exchange for high liquid filling ratio whereas below ≈16% a solution must be found to improve the heat exchange coefficient between the fluid and the cell walls. Our calculations are extended to the 80–120 K temperature range for nitrogen and argon in order to clarify the various parameters to take into account for an energy storage unit dimensioning.     

Unravel the Tangle: Atomistic Insight into Ultrahigh Curcumin-Loaded Polymer Micelles

Amphiphilic ABA-triblock copolymers, comprised of poly(2-oxazoline) and poly(2-oxazine), can solubilize poorly water-soluble molecules in a structure-dependent manner forming micelles with exceptionally high drug loading. All-atom molecular dynamics simulations are conducted on previously experimentally characterized, curcumin-loaded micelles to dissect the structure-property relationships. Polymer–drug interactions for different levels of drug loading and variation in polymer structures of both the inner hydrophobic core and outer hydrophilic shell are investigated. In silico, the system with the highest experimental loading capacity shows the highest number of drug molecules encapsulated by the core. Furthermore, in systems with lower loading capacity outer A blocks show a greater extent of entanglement with the inner B blocks. Hydrogen bond analyses corroborate previous hypotheses: poly(2-butyl-2-oxazoline) B blocks, found experimentally to have reduced loading capacity for curcumin compared to poly(2-propyl-2-oxazine), establish fewer but longer-lasting hydrogen bonds. This possibly results from different sidechain conformations around the hydrophobic cargo, which is investigated by unsupervised machine learning to cluster monomers in smaller model systems mimicking different micelle compartments. Exchanging poly(2-methyl-2-oxazoline) with poly(2-ethyl-2-oxazoline) leads to increased drug interactions and reduced corona hydration; this suggests an impairment of micelle solubility or colloidal stability. These observations can help driving forward a more rational a priori nanoformulation design.     

Long-term aging of Ag/a-C:H:O nanocomposite coatings in air and in aqueous environment

Nanocomposite coatings of silver particles embedded in a plasma polymer matrix possess interesting properties depending on their microstructure. The film microstructure is affected among others also by the RF power supplied during the deposition, as shown by transmission electron microscopy. The optical properties are characterized by UV–vis–NIR spectroscopy. An anomalous optical absorption peak from the Ag nanoparticles is observed and related to the microstructure of the nanocomposite films. Furthermore, a long-term aging of the coatings is studied in-depth in ambient air and in aqueous environments. It is shown that the studied films are not entirely stable. The deposition conditions and the microstructure of the films affect the processes taking place during their aging in both environments.